Articles

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BACKGROUND: Antibiotics are generally ineffective for patients with acute cough,¹ yet they continue to be prescribed frequently by primary care physicians. A recent observational study showed that delayed prescribing can reduce antibiotic use for such patients without leading to patient dissatisfaction, but symptom outcomes were not reported.²

POPULATION STUDIED: This study enrolled 191 patients older than 16 years who presented to 1 of 22 Scottish general practices with a primary complaint of acute cough with or without coryza, shortness of breath, sputum, fever, sore throat, or chest tightness. The researchers excluded 2 groups: patients expressing a strong preference for antibiotics or for whom the general practitioner (GP) would not have considered antibiotics.

STUDY DESIGN AND VALIDITY: This was an unblinded randomized controlled trial. The patients were assigned to 1 of 2 groups; the immediate group received an antibiotic prescription at the visit, and the delayed group had their prescription held at the reception desk for 2 weeks and were invited to pick it up at any time, if required. Outcomes were measured by patient questionnaires (78% return rate), physician questionnaires (98% return rate), and a chart review (88% of charts). The strengths of this study were a proper randomization procedure, adequate allocation concealment, an intention-to-treat analysis, and baseline similarity between groups in terms of symptoms and belief in antibiotics. Weaknesses included an unblinded study design and possible selection bias in both physician and patient recruitment (a minority of eligible practices participated, and the GPs taking part enrolled between 1 and 25 patients each). The study only recruited half the target number of patients, so the power to detect clinical differences between groups was less than anticipated.

OUTCOMES MEASURED: The number and timing of collected prescriptions in the delayed group were recorded. The patient questionnaire included daily presence of cough and other symptoms, satisfaction with the visit, and the patient’s intention of consulting for future similar illnesses. The physician questionnaire asked for impressions of the utility of and frequency with which patients subsequently used delayed prescribing. Chart reviews noted the number of return visits for similar illnesses in the subsequent 6 or more months.

RESULTS: Almost half (45%) of the patients in the delayed group picked up their prescriptions after an average of 6 days and were more likely to do so if they had persistent symptoms or were more worried about their cough. Beginning with day 4 following the visit, there was a nonstatistically significant trend in the persistence of cough between groups that widened on day 7 (75% in the delayed group still coughing compared with 55% in the immediate group) and narrowed on day 10. By day 14, a similar number of patients were still coughing (35% in the delayed group vs 30% in the immediate group). The authors state there were no differences in other symptoms (data not provided). Fewer patients in the delayed group were very satisfied with the visit (54% vs 73%; P=.03; number needed to harm [NNH]=5), and more were dissatisfied with the treatment (13% vs 0%; P=.001; NNH=8). Patients of the GPs who recruited fewer patients were more likely to be very satisfied than those of GPs who recruited more patients. Chart reviews did not reveal a difference in return visits between groups. Eighty-seven percent of the physicians described delayed prescription as a useful strategy, and 68% used this method at least monthly.

BACKGROUND: Antibiotics are generally ineffective for patients with acute cough,¹ yet they continue to be prescribed frequently by primary care physicians. A recent observational study showed that delayed prescribing can reduce antibiotic use for such patients without leading to patient dissatisfaction, but symptom outcomes were not reported.²

POPULATION STUDIED: This study enrolled 191 patients older than 16 years who presented to 1 of 22 Scottish general practices with a primary complaint of acute cough with or without coryza, shortness of breath, sputum, fever, sore throat, or chest tightness. The researchers excluded 2 groups: patients expressing a strong preference for antibiotics or for whom the general practitioner (GP) would not have considered antibiotics.

STUDY DESIGN AND VALIDITY: This was an unblinded randomized controlled trial. The patients were assigned to 1 of 2 groups; the immediate group received an antibiotic prescription at the visit, and the delayed group had their prescription held at the reception desk for 2 weeks and were invited to pick it up at any time, if required. Outcomes were measured by patient questionnaires (78% return rate), physician questionnaires (98% return rate), and a chart review (88% of charts). The strengths of this study were a proper randomization procedure, adequate allocation concealment, an intention-to-treat analysis, and baseline similarity between groups in terms of symptoms and belief in antibiotics. Weaknesses included an unblinded study design and possible selection bias in both physician and patient recruitment (a minority of eligible practices participated, and the GPs taking part enrolled between 1 and 25 patients each). The study only recruited half the target number of patients, so the power to detect clinical differences between groups was less than anticipated.

OUTCOMES MEASURED: The number and timing of collected prescriptions in the delayed group were recorded. The patient questionnaire included daily presence of cough and other symptoms, satisfaction with the visit, and the patient’s intention of consulting for future similar illnesses. The physician questionnaire asked for impressions of the utility of and frequency with which patients subsequently used delayed prescribing. Chart reviews noted the number of return visits for similar illnesses in the subsequent 6 or more months.

RESULTS: Almost half (45%) of the patients in the delayed group picked up their prescriptions after an average of 6 days and were more likely to do so if they had persistent symptoms or were more worried about their cough. Beginning with day 4 following the visit, there was a nonstatistically significant trend in the persistence of cough between groups that widened on day 7 (75% in the delayed group still coughing compared with 55% in the immediate group) and narrowed on day 10. By day 14, a similar number of patients were still coughing (35% in the delayed group vs 30% in the immediate group). The authors state there were no differences in other symptoms (data not provided). Fewer patients in the delayed group were very satisfied with the visit (54% vs 73%; P=.03; number needed to harm [NNH]=5), and more were dissatisfied with the treatment (13% vs 0%; P=.001; NNH=8). Patients of the GPs who recruited fewer patients were more likely to be very satisfied than those of GPs who recruited more patients. Chart reviews did not reveal a difference in return visits between groups. Eighty-seven percent of the physicians described delayed prescription as a useful strategy, and 68% used this method at least monthly.

BACKGROUND: Antibiotics are generally ineffective for patients with acute cough,¹ yet they continue to be prescribed frequently by primary care physicians. A recent observational study showed that delayed prescribing can reduce antibiotic use for such patients without leading to patient dissatisfaction, but symptom outcomes were not reported.²

POPULATION STUDIED: This study enrolled 191 patients older than 16 years who presented to 1 of 22 Scottish general practices with a primary complaint of acute cough with or without coryza, shortness of breath, sputum, fever, sore throat, or chest tightness. The researchers excluded 2 groups: patients expressing a strong preference for antibiotics or for whom the general practitioner (GP) would not have considered antibiotics.

STUDY DESIGN AND VALIDITY: This was an unblinded randomized controlled trial. The patients were assigned to 1 of 2 groups; the immediate group received an antibiotic prescription at the visit, and the delayed group had their prescription held at the reception desk for 2 weeks and were invited to pick it up at any time, if required. Outcomes were measured by patient questionnaires (78% return rate), physician questionnaires (98% return rate), and a chart review (88% of charts). The strengths of this study were a proper randomization procedure, adequate allocation concealment, an intention-to-treat analysis, and baseline similarity between groups in terms of symptoms and belief in antibiotics. Weaknesses included an unblinded study design and possible selection bias in both physician and patient recruitment (a minority of eligible practices participated, and the GPs taking part enrolled between 1 and 25 patients each). The study only recruited half the target number of patients, so the power to detect clinical differences between groups was less than anticipated.

OUTCOMES MEASURED: The number and timing of collected prescriptions in the delayed group were recorded. The patient questionnaire included daily presence of cough and other symptoms, satisfaction with the visit, and the patient’s intention of consulting for future similar illnesses. The physician questionnaire asked for impressions of the utility of and frequency with which patients subsequently used delayed prescribing. Chart reviews noted the number of return visits for similar illnesses in the subsequent 6 or more months.

RESULTS: Almost half (45%) of the patients in the delayed group picked up their prescriptions after an average of 6 days and were more likely to do so if they had persistent symptoms or were more worried about their cough. Beginning with day 4 following the visit, there was a nonstatistically significant trend in the persistence of cough between groups that widened on day 7 (75% in the delayed group still coughing compared with 55% in the immediate group) and narrowed on day 10. By day 14, a similar number of patients were still coughing (35% in the delayed group vs 30% in the immediate group). The authors state there were no differences in other symptoms (data not provided). Fewer patients in the delayed group were very satisfied with the visit (54% vs 73%; P=.03; number needed to harm [NNH]=5), and more were dissatisfied with the treatment (13% vs 0%; P=.001; NNH=8). Patients of the GPs who recruited fewer patients were more likely to be very satisfied than those of GPs who recruited more patients. Chart reviews did not reveal a difference in return visits between groups. Eighty-seven percent of the physicians described delayed prescription as a useful strategy, and 68% used this method at least monthly.

BACKGROUND: Recent meta-analyses have concluded that steroids ameliorate croup, but questions remain about the effectiveness of oral dosing.

POPULATION STUDIED: A total of 277 children with moderate croup were enrolled from a pediatric emergency department of an academic medical center. Moderate croup was defined as hoarseness and barking cough associated with retractions or stridor at rest. Children with mild disease—barky cough only without retractions—or with severe croup—with cyanosis, severe retractions, or altered mental status—were excluded. Other exclusions were reactive airway exacerbation, epiglotitis, pneumonia, upper airway anomalies, immunosupression, recent steroids, or symptoms present for more than 48 hours. The mean age was 2 years; 69% were men. Eighty-five percent had the illness for more than 24 hours, and 66% had a fever. Thus, the patients seem similar to those seen in family practice offices, but more information about the referral pattern, socioeconomic status, diagnostic work-up, or clinical status would be very valuable in assessing the generalizability of this trial to nonacademic emergency department settings.

STUDY DESIGN AND VALIDITY: This was a single-blinded randomized controlled study. Patients were randomized to a single dose of dexamethasone (0.6 mg/kg, maximum dose 8 mg) administered either orally or intramuscularly (IM). The oral medication was administrated as a crushed tablet mixed with flavored syrup or jelly. Nurses and parents knew the treatment status; physicians assessing the child after treatment were unaware of the mode of administration. After discharge no routine follow-up appointment was given, but an investigator masked to treatment assignment telephoned caretakers at 48 to 72 hours after treatment to determine unscheduled returns for treatment and the child’s clinical status. The sample size was calculated on the basis of a power of 0.8 to detect a 10% difference of return visits. Student t test and chi squares were used to analyze data.

OUTCOMES MEASURED: The primary outcome was parental report of return for further care after discharge. Unscheduled returns were defined as the subsequent need for additional steroids, racemic epinephrine, and/or hospitalization. A secondary outcome was the caregiver assessment of symptom improvement at 48 to 72 hours. Outcomes important for primary care providers were not measured, such as caretaker satisfaction with treatment; missed school, daycare, or work; or costs for parents or for the hospital.

RESULTS: The groups were similar at the outset. There were no statistically significant differences between patients receiving IM versus oral dexamethasone in unscheduled returns (32% vs 25%, respectively) or unscheduled return failures (8% vs 9%, respectively), and there was no difference in caretaker reports of symptomatic improvement. Only 1 of 138 children in the oral group had emesis. Patients receiving racemic epinephrine at the first visit were more likely to return, regardless of the route of dexamethasone administration.

BACKGROUND: Recent meta-analyses have concluded that steroids ameliorate croup, but questions remain about the effectiveness of oral dosing.

POPULATION STUDIED: A total of 277 children with moderate croup were enrolled from a pediatric emergency department of an academic medical center. Moderate croup was defined as hoarseness and barking cough associated with retractions or stridor at rest. Children with mild disease—barky cough only without retractions—or with severe croup—with cyanosis, severe retractions, or altered mental status—were excluded. Other exclusions were reactive airway exacerbation, epiglotitis, pneumonia, upper airway anomalies, immunosupression, recent steroids, or symptoms present for more than 48 hours. The mean age was 2 years; 69% were men. Eighty-five percent had the illness for more than 24 hours, and 66% had a fever. Thus, the patients seem similar to those seen in family practice offices, but more information about the referral pattern, socioeconomic status, diagnostic work-up, or clinical status would be very valuable in assessing the generalizability of this trial to nonacademic emergency department settings.

STUDY DESIGN AND VALIDITY: This was a single-blinded randomized controlled study. Patients were randomized to a single dose of dexamethasone (0.6 mg/kg, maximum dose 8 mg) administered either orally or intramuscularly (IM). The oral medication was administrated as a crushed tablet mixed with flavored syrup or jelly. Nurses and parents knew the treatment status; physicians assessing the child after treatment were unaware of the mode of administration. After discharge no routine follow-up appointment was given, but an investigator masked to treatment assignment telephoned caretakers at 48 to 72 hours after treatment to determine unscheduled returns for treatment and the child’s clinical status. The sample size was calculated on the basis of a power of 0.8 to detect a 10% difference of return visits. Student t test and chi squares were used to analyze data.

OUTCOMES MEASURED: The primary outcome was parental report of return for further care after discharge. Unscheduled returns were defined as the subsequent need for additional steroids, racemic epinephrine, and/or hospitalization. A secondary outcome was the caregiver assessment of symptom improvement at 48 to 72 hours. Outcomes important for primary care providers were not measured, such as caretaker satisfaction with treatment; missed school, daycare, or work; or costs for parents or for the hospital.

RESULTS: The groups were similar at the outset. There were no statistically significant differences between patients receiving IM versus oral dexamethasone in unscheduled returns (32% vs 25%, respectively) or unscheduled return failures (8% vs 9%, respectively), and there was no difference in caretaker reports of symptomatic improvement. Only 1 of 138 children in the oral group had emesis. Patients receiving racemic epinephrine at the first visit were more likely to return, regardless of the route of dexamethasone administration.

BACKGROUND: Recent meta-analyses have concluded that steroids ameliorate croup, but questions remain about the effectiveness of oral dosing.

POPULATION STUDIED: A total of 277 children with moderate croup were enrolled from a pediatric emergency department of an academic medical center. Moderate croup was defined as hoarseness and barking cough associated with retractions or stridor at rest. Children with mild disease—barky cough only without retractions—or with severe croup—with cyanosis, severe retractions, or altered mental status—were excluded. Other exclusions were reactive airway exacerbation, epiglotitis, pneumonia, upper airway anomalies, immunosupression, recent steroids, or symptoms present for more than 48 hours. The mean age was 2 years; 69% were men. Eighty-five percent had the illness for more than 24 hours, and 66% had a fever. Thus, the patients seem similar to those seen in family practice offices, but more information about the referral pattern, socioeconomic status, diagnostic work-up, or clinical status would be very valuable in assessing the generalizability of this trial to nonacademic emergency department settings.

STUDY DESIGN AND VALIDITY: This was a single-blinded randomized controlled study. Patients were randomized to a single dose of dexamethasone (0.6 mg/kg, maximum dose 8 mg) administered either orally or intramuscularly (IM). The oral medication was administrated as a crushed tablet mixed with flavored syrup or jelly. Nurses and parents knew the treatment status; physicians assessing the child after treatment were unaware of the mode of administration. After discharge no routine follow-up appointment was given, but an investigator masked to treatment assignment telephoned caretakers at 48 to 72 hours after treatment to determine unscheduled returns for treatment and the child’s clinical status. The sample size was calculated on the basis of a power of 0.8 to detect a 10% difference of return visits. Student t test and chi squares were used to analyze data.

OUTCOMES MEASURED: The primary outcome was parental report of return for further care after discharge. Unscheduled returns were defined as the subsequent need for additional steroids, racemic epinephrine, and/or hospitalization. A secondary outcome was the caregiver assessment of symptom improvement at 48 to 72 hours. Outcomes important for primary care providers were not measured, such as caretaker satisfaction with treatment; missed school, daycare, or work; or costs for parents or for the hospital.

RESULTS: The groups were similar at the outset. There were no statistically significant differences between patients receiving IM versus oral dexamethasone in unscheduled returns (32% vs 25%, respectively) or unscheduled return failures (8% vs 9%, respectively), and there was no difference in caretaker reports of symptomatic improvement. Only 1 of 138 children in the oral group had emesis. Patients receiving racemic epinephrine at the first visit were more likely to return, regardless of the route of dexamethasone administration.

BACKGROUND: Of the 10 published randomized controlled trials, only 5 reported that zinc lozenges reduced the duration of cold symptoms. The reasons for the different results among these trials include differences in doses, salts, and formulations of zinc lozenges; differences in study design; and difficulty in truly blinding study participants.

POPULATION STUDIED: Fifty ambulatory volunteers older than 18 years were recruited within 24 hours of developing cold symptoms. Potential participants were students, staff, or employees of Wayne State University who had at least 2 of 10 cold symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever. Exclusion criteria included pregnancy, immunodeficiency disorder, any chronic illness, and previous use of zinc lozenges. The treatment groups did not differ significantly in terms of age (37±11 years), however, more patients receiving placebo were smokers (35% vs 20%) and had an allergy history (15% vs 8%).

STUDY DESIGN AND VALIDITY: The appropriate study design was used for this efficacy trial. Two patients in the placebo group dropped out on day 2; all other patients completed the study and were included in the analysis. The patients, the research consultant preparing the randomization code and packages of medications, and a research assistant distributing the study medication were not aware of treatment assignment (ie, allocation was concealed).

OUTCOMES MEASURED: Both patient-oriented (cold symptoms) and disease-oriented (plasma levels of zinc and cytokines) outcomes were used to assess the patients. The primary outcome was average duration of cold symptoms.

RESULTS: Zinc-treated patients had lower overall severity scores (P <.002, test for treatment x time interaction), as well as a significantly shorter mean duration of all cold symptoms, 4.5 versus 8.1 days (3.6-day difference; 95% confidence interval, 2.6-4.6 days; P <.01). By day 4, the average severity score in the zinc group was half that in the placebo group (2.7 vs 5.4 out of a possible 30). Of the 10 measured cold symptoms, only the duration of nasal discharge and cough were significantly shorter in the zinc-treated patients. The average number of lozenges taken per day did not differ between treatment groups (6.2 for zinc and 5.8 for placebo). Patients in the zinc group had a statistically significant higher incidence of dry mouth (P=.003) and constipation (P=.02). Although it did not reach statistical significance, zinc-treated patients experienced more bad taste (52% vs 26%, P=.08).

BACKGROUND: Of the 10 published randomized controlled trials, only 5 reported that zinc lozenges reduced the duration of cold symptoms. The reasons for the different results among these trials include differences in doses, salts, and formulations of zinc lozenges; differences in study design; and difficulty in truly blinding study participants.

POPULATION STUDIED: Fifty ambulatory volunteers older than 18 years were recruited within 24 hours of developing cold symptoms. Potential participants were students, staff, or employees of Wayne State University who had at least 2 of 10 cold symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever. Exclusion criteria included pregnancy, immunodeficiency disorder, any chronic illness, and previous use of zinc lozenges. The treatment groups did not differ significantly in terms of age (37±11 years), however, more patients receiving placebo were smokers (35% vs 20%) and had an allergy history (15% vs 8%).

STUDY DESIGN AND VALIDITY: The appropriate study design was used for this efficacy trial. Two patients in the placebo group dropped out on day 2; all other patients completed the study and were included in the analysis. The patients, the research consultant preparing the randomization code and packages of medications, and a research assistant distributing the study medication were not aware of treatment assignment (ie, allocation was concealed).

OUTCOMES MEASURED: Both patient-oriented (cold symptoms) and disease-oriented (plasma levels of zinc and cytokines) outcomes were used to assess the patients. The primary outcome was average duration of cold symptoms.

RESULTS: Zinc-treated patients had lower overall severity scores (P <.002, test for treatment x time interaction), as well as a significantly shorter mean duration of all cold symptoms, 4.5 versus 8.1 days (3.6-day difference; 95% confidence interval, 2.6-4.6 days; P <.01). By day 4, the average severity score in the zinc group was half that in the placebo group (2.7 vs 5.4 out of a possible 30). Of the 10 measured cold symptoms, only the duration of nasal discharge and cough were significantly shorter in the zinc-treated patients. The average number of lozenges taken per day did not differ between treatment groups (6.2 for zinc and 5.8 for placebo). Patients in the zinc group had a statistically significant higher incidence of dry mouth (P=.003) and constipation (P=.02). Although it did not reach statistical significance, zinc-treated patients experienced more bad taste (52% vs 26%, P=.08).

BACKGROUND: Of the 10 published randomized controlled trials, only 5 reported that zinc lozenges reduced the duration of cold symptoms. The reasons for the different results among these trials include differences in doses, salts, and formulations of zinc lozenges; differences in study design; and difficulty in truly blinding study participants.

POPULATION STUDIED: Fifty ambulatory volunteers older than 18 years were recruited within 24 hours of developing cold symptoms. Potential participants were students, staff, or employees of Wayne State University who had at least 2 of 10 cold symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever. Exclusion criteria included pregnancy, immunodeficiency disorder, any chronic illness, and previous use of zinc lozenges. The treatment groups did not differ significantly in terms of age (37±11 years), however, more patients receiving placebo were smokers (35% vs 20%) and had an allergy history (15% vs 8%).

STUDY DESIGN AND VALIDITY: The appropriate study design was used for this efficacy trial. Two patients in the placebo group dropped out on day 2; all other patients completed the study and were included in the analysis. The patients, the research consultant preparing the randomization code and packages of medications, and a research assistant distributing the study medication were not aware of treatment assignment (ie, allocation was concealed).

OUTCOMES MEASURED: Both patient-oriented (cold symptoms) and disease-oriented (plasma levels of zinc and cytokines) outcomes were used to assess the patients. The primary outcome was average duration of cold symptoms.

RESULTS: Zinc-treated patients had lower overall severity scores (P <.002, test for treatment x time interaction), as well as a significantly shorter mean duration of all cold symptoms, 4.5 versus 8.1 days (3.6-day difference; 95% confidence interval, 2.6-4.6 days; P <.01). By day 4, the average severity score in the zinc group was half that in the placebo group (2.7 vs 5.4 out of a possible 30). Of the 10 measured cold symptoms, only the duration of nasal discharge and cough were significantly shorter in the zinc-treated patients. The average number of lozenges taken per day did not differ between treatment groups (6.2 for zinc and 5.8 for placebo). Patients in the zinc group had a statistically significant higher incidence of dry mouth (P=.003) and constipation (P=.02). Although it did not reach statistical significance, zinc-treated patients experienced more bad taste (52% vs 26%, P=.08).

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.