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Amoxicillin-clavulanate ineffective for suspected acute sinusitis
Amoxicillin-clavulanate was no more effective than placebo in quickly relieving symptoms in patients diagnosed clinically with acute sinusitis in a general practice setting. It was, however, much more likely to cause diarrhea. Because most patients will improve spontaneously, antibiotics should be reserved for patients with prolonged symptoms. An inexpensive, narrow-spectrum drug such as amoxicillin is a good initial choice.
Amoxicillin-clavulanate was no more effective than placebo in quickly relieving symptoms in patients diagnosed clinically with acute sinusitis in a general practice setting. It was, however, much more likely to cause diarrhea. Because most patients will improve spontaneously, antibiotics should be reserved for patients with prolonged symptoms. An inexpensive, narrow-spectrum drug such as amoxicillin is a good initial choice.
Amoxicillin-clavulanate was no more effective than placebo in quickly relieving symptoms in patients diagnosed clinically with acute sinusitis in a general practice setting. It was, however, much more likely to cause diarrhea. Because most patients will improve spontaneously, antibiotics should be reserved for patients with prolonged symptoms. An inexpensive, narrow-spectrum drug such as amoxicillin is a good initial choice.
Warfarin started at 10 mg achieves therapeutic INR faster than 5 mg
Starting warfarin with 10 mg rather than 5 mg achieves a therapeutic international normalized ratio (INR) >1.9 one day earlier (4.2 vs 5.6 days) in selected outpatients at low risk for major bleeding complications with confirmed acute venous thromboembolism.
This strategy saves the time and expense of 1 daily INR determination, and it may decrease the number of days that low-molecular-weight heparin is required by 1 day— although all patients in this study, due to the nature of the design, received a minimum of 5 days of low-molecular-weight heparin.
No conclusions regarding differences in safety or efficacy between the 10-mg and 5-mg nomogram can be drawn from the results of this study, as it was underpowered to detect differences in these important endpoints.
Starting warfarin with 10 mg rather than 5 mg achieves a therapeutic international normalized ratio (INR) >1.9 one day earlier (4.2 vs 5.6 days) in selected outpatients at low risk for major bleeding complications with confirmed acute venous thromboembolism.
This strategy saves the time and expense of 1 daily INR determination, and it may decrease the number of days that low-molecular-weight heparin is required by 1 day— although all patients in this study, due to the nature of the design, received a minimum of 5 days of low-molecular-weight heparin.
No conclusions regarding differences in safety or efficacy between the 10-mg and 5-mg nomogram can be drawn from the results of this study, as it was underpowered to detect differences in these important endpoints.
Starting warfarin with 10 mg rather than 5 mg achieves a therapeutic international normalized ratio (INR) >1.9 one day earlier (4.2 vs 5.6 days) in selected outpatients at low risk for major bleeding complications with confirmed acute venous thromboembolism.
This strategy saves the time and expense of 1 daily INR determination, and it may decrease the number of days that low-molecular-weight heparin is required by 1 day— although all patients in this study, due to the nature of the design, received a minimum of 5 days of low-molecular-weight heparin.
No conclusions regarding differences in safety or efficacy between the 10-mg and 5-mg nomogram can be drawn from the results of this study, as it was underpowered to detect differences in these important endpoints.
What is the best NSAID regimen for arthritis patients with bleeding ulcer?
Among arthritis patients with a recent history of bleeding ulcer, celecoxib was just as likely as diclofenac plus omeprazole to cause recurrent bleeding. The effectiveness of these two regimens in preventing recurrent bleeding compared with a general nonsteroidal antiinflammatory drug (NSAID) used alone cannot be determined from this study. Unfortunately, adverse renal effects were common with both regimens.
Among arthritis patients with a recent history of bleeding ulcer, celecoxib was just as likely as diclofenac plus omeprazole to cause recurrent bleeding. The effectiveness of these two regimens in preventing recurrent bleeding compared with a general nonsteroidal antiinflammatory drug (NSAID) used alone cannot be determined from this study. Unfortunately, adverse renal effects were common with both regimens.
Among arthritis patients with a recent history of bleeding ulcer, celecoxib was just as likely as diclofenac plus omeprazole to cause recurrent bleeding. The effectiveness of these two regimens in preventing recurrent bleeding compared with a general nonsteroidal antiinflammatory drug (NSAID) used alone cannot be determined from this study. Unfortunately, adverse renal effects were common with both regimens.
Does long-term use of sibutramine (Meridia) result in continued weight loss in short-term responders?
Is ginger root effective for decreasing the severity of nausea and vomiting in early pregnancy?
BACKGROUND: Nausea and vomiting are both common and a source of distress for women in early pregnancy. As the cause is uncertain, numerous treatments are used empirically. Natural products are appealing because of the concern about teratogenic effects of drugs.
POPULATION STUDIED: New obstetric patients with nausea and vomiting of pregnancy were recruited for this study. Women were enrolled at or before 17 weeks’ gestation, during their first visit to an antenatal clinic in Thailand. Patients were not studied if they had other conditions that manifest with nausea or vomiting, reported current use of medications that might cause or relieve nausea or vomiting, had an inability to take medications as prescribed, and if they had mental retardation. The treatment groups did not differ significantly in terms of age (mean = 28 years), parity, gestational age (mean = 10 weeks), education, or baseline assessment of symptoms.
STUDY DESIGN AND VALIDITY: Seventy eligible women received either oral ginger 250 mg before meals and at bedtime (1 g per day) or an identical-appearing placebo for 4 days in this well-designed prospective randomized double-blind trial. Fresh ginger root was chopped, baked, ground into powder, weighed, and packed into capsules by a pharmacist for the study. Women graded nausea severity on a visual analog scale on their first study visit (baseline) and twice daily for the following 4 days, and also recorded the number of vomiting episodes in the 24 hours before treatment and each day afterward. Also, a 5-item Likert scale was used to assess the change in severity of nausea at a follow-up visit 1 week later.The appropriate study design was used for this efficacy trial. Three patients in the placebo group failed to return for follow-up visits; all other subjects completed the study and were included in the analysis. To be certain that excluding the 3 patients from the analysis did not bias the results, an intention-to-treat analysis was performed in which the symptoms of the 3 dropouts in the placebo group were assumed to improve as much as the best response in the ginger group. Concealed allocation of randomized treatment was assured by keeping treatment codes in sequence in sealed black envelopes.
OUTCOMES MEASURED: The primary outcomes were improvement in nausea symptoms (using 2 measurement scales) and decrease in vomiting episodes. Secondary outcomes included side effects and adverse effects on pregnancy outcomes (miscarriage, preterm delivery).
RESULTS: Compared with placebo, the ginger group had significantly lower nausea scores on days 3 (P=.031) and 4 (P=.05), and for the entire treatment period (P=.014). By intention-to-treat analysis (including the 3 dropouts from the placebo group), the ginger group had significantly lower nausea scores only on day 4 of treatment (P=.035). After 4 days of treatment, the proportion of women with vomiting in the ginger group was significantly lower than in the placebo group (37.5% vs 65.7%, P=.021). The number of vomiting episodes decreased significantly over the 4-day treatment period in the ginger group (1.4 ± 1.4) compared with the placebo group (0.3 ± 1.1, P<.001). These results were unchanged using intention-to-treat analysis. Using a Likert scale to assess change in severity of nausea, 87.5% of the ginger-treated women reported improvement compared with 28% in the placebo group (P <.001). Again, results remained statistically significant using intention-to-treat analysis. No important side effects or adverse effects of ginger on pregnancy outcome were noted in this study.
This very brief (4 days) well-designed study demonstrates that an extemporaneous preparation of ginger root powder is well tolerated and helps relieve the severity of nausea and decreases vomiting episodes in early pregnancy. The usual caveat applies regarding herbal products: Since ginger products are not standardized or regulated, the results obtained by the various products marketed in the United States may vary from these results The dose used in this study is within the range (1-2 g/day) generally recommended for ginger’s anti-emetic effect.1 Although the length of the study was too brief to provide meaningful information regarding its safe use in pregnancy, the long history of this herb’s use in traditional Chinese medicine is reassuring.
BACKGROUND: Nausea and vomiting are both common and a source of distress for women in early pregnancy. As the cause is uncertain, numerous treatments are used empirically. Natural products are appealing because of the concern about teratogenic effects of drugs.
POPULATION STUDIED: New obstetric patients with nausea and vomiting of pregnancy were recruited for this study. Women were enrolled at or before 17 weeks’ gestation, during their first visit to an antenatal clinic in Thailand. Patients were not studied if they had other conditions that manifest with nausea or vomiting, reported current use of medications that might cause or relieve nausea or vomiting, had an inability to take medications as prescribed, and if they had mental retardation. The treatment groups did not differ significantly in terms of age (mean = 28 years), parity, gestational age (mean = 10 weeks), education, or baseline assessment of symptoms.
STUDY DESIGN AND VALIDITY: Seventy eligible women received either oral ginger 250 mg before meals and at bedtime (1 g per day) or an identical-appearing placebo for 4 days in this well-designed prospective randomized double-blind trial. Fresh ginger root was chopped, baked, ground into powder, weighed, and packed into capsules by a pharmacist for the study. Women graded nausea severity on a visual analog scale on their first study visit (baseline) and twice daily for the following 4 days, and also recorded the number of vomiting episodes in the 24 hours before treatment and each day afterward. Also, a 5-item Likert scale was used to assess the change in severity of nausea at a follow-up visit 1 week later.The appropriate study design was used for this efficacy trial. Three patients in the placebo group failed to return for follow-up visits; all other subjects completed the study and were included in the analysis. To be certain that excluding the 3 patients from the analysis did not bias the results, an intention-to-treat analysis was performed in which the symptoms of the 3 dropouts in the placebo group were assumed to improve as much as the best response in the ginger group. Concealed allocation of randomized treatment was assured by keeping treatment codes in sequence in sealed black envelopes.
OUTCOMES MEASURED: The primary outcomes were improvement in nausea symptoms (using 2 measurement scales) and decrease in vomiting episodes. Secondary outcomes included side effects and adverse effects on pregnancy outcomes (miscarriage, preterm delivery).
RESULTS: Compared with placebo, the ginger group had significantly lower nausea scores on days 3 (P=.031) and 4 (P=.05), and for the entire treatment period (P=.014). By intention-to-treat analysis (including the 3 dropouts from the placebo group), the ginger group had significantly lower nausea scores only on day 4 of treatment (P=.035). After 4 days of treatment, the proportion of women with vomiting in the ginger group was significantly lower than in the placebo group (37.5% vs 65.7%, P=.021). The number of vomiting episodes decreased significantly over the 4-day treatment period in the ginger group (1.4 ± 1.4) compared with the placebo group (0.3 ± 1.1, P<.001). These results were unchanged using intention-to-treat analysis. Using a Likert scale to assess change in severity of nausea, 87.5% of the ginger-treated women reported improvement compared with 28% in the placebo group (P <.001). Again, results remained statistically significant using intention-to-treat analysis. No important side effects or adverse effects of ginger on pregnancy outcome were noted in this study.
This very brief (4 days) well-designed study demonstrates that an extemporaneous preparation of ginger root powder is well tolerated and helps relieve the severity of nausea and decreases vomiting episodes in early pregnancy. The usual caveat applies regarding herbal products: Since ginger products are not standardized or regulated, the results obtained by the various products marketed in the United States may vary from these results The dose used in this study is within the range (1-2 g/day) generally recommended for ginger’s anti-emetic effect.1 Although the length of the study was too brief to provide meaningful information regarding its safe use in pregnancy, the long history of this herb’s use in traditional Chinese medicine is reassuring.
BACKGROUND: Nausea and vomiting are both common and a source of distress for women in early pregnancy. As the cause is uncertain, numerous treatments are used empirically. Natural products are appealing because of the concern about teratogenic effects of drugs.
POPULATION STUDIED: New obstetric patients with nausea and vomiting of pregnancy were recruited for this study. Women were enrolled at or before 17 weeks’ gestation, during their first visit to an antenatal clinic in Thailand. Patients were not studied if they had other conditions that manifest with nausea or vomiting, reported current use of medications that might cause or relieve nausea or vomiting, had an inability to take medications as prescribed, and if they had mental retardation. The treatment groups did not differ significantly in terms of age (mean = 28 years), parity, gestational age (mean = 10 weeks), education, or baseline assessment of symptoms.
STUDY DESIGN AND VALIDITY: Seventy eligible women received either oral ginger 250 mg before meals and at bedtime (1 g per day) or an identical-appearing placebo for 4 days in this well-designed prospective randomized double-blind trial. Fresh ginger root was chopped, baked, ground into powder, weighed, and packed into capsules by a pharmacist for the study. Women graded nausea severity on a visual analog scale on their first study visit (baseline) and twice daily for the following 4 days, and also recorded the number of vomiting episodes in the 24 hours before treatment and each day afterward. Also, a 5-item Likert scale was used to assess the change in severity of nausea at a follow-up visit 1 week later.The appropriate study design was used for this efficacy trial. Three patients in the placebo group failed to return for follow-up visits; all other subjects completed the study and were included in the analysis. To be certain that excluding the 3 patients from the analysis did not bias the results, an intention-to-treat analysis was performed in which the symptoms of the 3 dropouts in the placebo group were assumed to improve as much as the best response in the ginger group. Concealed allocation of randomized treatment was assured by keeping treatment codes in sequence in sealed black envelopes.
OUTCOMES MEASURED: The primary outcomes were improvement in nausea symptoms (using 2 measurement scales) and decrease in vomiting episodes. Secondary outcomes included side effects and adverse effects on pregnancy outcomes (miscarriage, preterm delivery).
RESULTS: Compared with placebo, the ginger group had significantly lower nausea scores on days 3 (P=.031) and 4 (P=.05), and for the entire treatment period (P=.014). By intention-to-treat analysis (including the 3 dropouts from the placebo group), the ginger group had significantly lower nausea scores only on day 4 of treatment (P=.035). After 4 days of treatment, the proportion of women with vomiting in the ginger group was significantly lower than in the placebo group (37.5% vs 65.7%, P=.021). The number of vomiting episodes decreased significantly over the 4-day treatment period in the ginger group (1.4 ± 1.4) compared with the placebo group (0.3 ± 1.1, P<.001). These results were unchanged using intention-to-treat analysis. Using a Likert scale to assess change in severity of nausea, 87.5% of the ginger-treated women reported improvement compared with 28% in the placebo group (P <.001). Again, results remained statistically significant using intention-to-treat analysis. No important side effects or adverse effects of ginger on pregnancy outcome were noted in this study.
This very brief (4 days) well-designed study demonstrates that an extemporaneous preparation of ginger root powder is well tolerated and helps relieve the severity of nausea and decreases vomiting episodes in early pregnancy. The usual caveat applies regarding herbal products: Since ginger products are not standardized or regulated, the results obtained by the various products marketed in the United States may vary from these results The dose used in this study is within the range (1-2 g/day) generally recommended for ginger’s anti-emetic effect.1 Although the length of the study was too brief to provide meaningful information regarding its safe use in pregnancy, the long history of this herb’s use in traditional Chinese medicine is reassuring.
Is an extract of the fruit of agnus castus (chaste tree or chasteberry) effective for prevention of symptoms of premenstrual syndrome (PMS)?
BACKGROUND: PMS is both common and troublesome, and there is no consensus on the most tolerable and effective therapy. Chasteberry fruit is commonly used in Europe for this condition. Given the strong placebo response noted with PMS1 and the increasing popularity and availability of herbal formulations in the United States, carefully controlled trials are needed to assess these new treatment options.
POPULATION STUDIED: Six general medicine outpatient clinics in Germany recruited 178 women aged 18 years or older with PMS as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Exclusion criteria included psychotherapy, any serious medical condition, pregnancy, breast-feeding, inadequate contraception, alcohol or drug dependence, hypersensitivity to chasteberry, fever, pituitary disease, or use of sex hormones other than oral contraceptives. The treatment groups did not differ significantly in terms of age (mean=36 years), weight, cycle characteristics, or initial assessments of severity.
STUDY DESIGN AND VALIDITY: In this prospective randomized double-blind placebo-controlled trial, participants received either a chasteberry (ZE 440) 20-mg tablet standardized for casticin (one of the presumed active principles) or matching placebo once daily. The authors assessed efficacy by comparing validated self-assessment scales at baseline (beginning of first menstrual cycle) and at the end of the third cycle. Tolerability was assessed using side effects reported at the last study visit, rather than by recording in a daily diary.
OUTCOMES MEASURED: The primary outcome was the change from baseline to end point in a combined score of 6 self-assessment items rated on a visual analog scale (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast fullness). The secondary outcomes included each of the 6 items independently, 3 global assessment items (corroborated by physicians), and the responder rate, defined as 50% or more reduction in self-assessed symptoms from baseline.
RESULTS: Compared with placebo, patients who received chasteberry had a significant improvement in the combined symptom score (P <.001). In 5 of the 6 self-assessment items (irritability, mood alteration, anger, headache, and breast fullness), chasteberry was more effective than placebo (P <.01), with “other symptoms including bloating” being unaffected by treatment. All 3 global assessment items significantly favored the treated group, as did the responder rate (52% vs 24%, no statistical analysis presented). These results remained unchanged by subgroup analyses that excluded women taking oral contraceptives and included the 8 women initially screened but without postbaseline values who were removed from the initial intention-to-treat population. Side effect rates were similar in the 2 groups; all were mild, and none led to discontinuation.
The formulation of chasteberry used in this appropriately designed study was well tolerated and more effective than placebo in decreasing symptoms of PMS. Most symptoms of PMS significantly improved with active treatment, and slightly more than half the women taking this herb experienced a substantial (>50%) decrease in overall symptoms. Because of reduced Food and Drug Administration oversight of the manufacturing of herbal medicines in the United States, we cannot be certain that our patients have access to chasteberry extract similar to the one used in this study. If such a product can be found, it can be recommended as one of the initial treatments for this common and troublesome condition.
BACKGROUND: PMS is both common and troublesome, and there is no consensus on the most tolerable and effective therapy. Chasteberry fruit is commonly used in Europe for this condition. Given the strong placebo response noted with PMS1 and the increasing popularity and availability of herbal formulations in the United States, carefully controlled trials are needed to assess these new treatment options.
POPULATION STUDIED: Six general medicine outpatient clinics in Germany recruited 178 women aged 18 years or older with PMS as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Exclusion criteria included psychotherapy, any serious medical condition, pregnancy, breast-feeding, inadequate contraception, alcohol or drug dependence, hypersensitivity to chasteberry, fever, pituitary disease, or use of sex hormones other than oral contraceptives. The treatment groups did not differ significantly in terms of age (mean=36 years), weight, cycle characteristics, or initial assessments of severity.
STUDY DESIGN AND VALIDITY: In this prospective randomized double-blind placebo-controlled trial, participants received either a chasteberry (ZE 440) 20-mg tablet standardized for casticin (one of the presumed active principles) or matching placebo once daily. The authors assessed efficacy by comparing validated self-assessment scales at baseline (beginning of first menstrual cycle) and at the end of the third cycle. Tolerability was assessed using side effects reported at the last study visit, rather than by recording in a daily diary.
OUTCOMES MEASURED: The primary outcome was the change from baseline to end point in a combined score of 6 self-assessment items rated on a visual analog scale (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast fullness). The secondary outcomes included each of the 6 items independently, 3 global assessment items (corroborated by physicians), and the responder rate, defined as 50% or more reduction in self-assessed symptoms from baseline.
RESULTS: Compared with placebo, patients who received chasteberry had a significant improvement in the combined symptom score (P <.001). In 5 of the 6 self-assessment items (irritability, mood alteration, anger, headache, and breast fullness), chasteberry was more effective than placebo (P <.01), with “other symptoms including bloating” being unaffected by treatment. All 3 global assessment items significantly favored the treated group, as did the responder rate (52% vs 24%, no statistical analysis presented). These results remained unchanged by subgroup analyses that excluded women taking oral contraceptives and included the 8 women initially screened but without postbaseline values who were removed from the initial intention-to-treat population. Side effect rates were similar in the 2 groups; all were mild, and none led to discontinuation.
The formulation of chasteberry used in this appropriately designed study was well tolerated and more effective than placebo in decreasing symptoms of PMS. Most symptoms of PMS significantly improved with active treatment, and slightly more than half the women taking this herb experienced a substantial (>50%) decrease in overall symptoms. Because of reduced Food and Drug Administration oversight of the manufacturing of herbal medicines in the United States, we cannot be certain that our patients have access to chasteberry extract similar to the one used in this study. If such a product can be found, it can be recommended as one of the initial treatments for this common and troublesome condition.
BACKGROUND: PMS is both common and troublesome, and there is no consensus on the most tolerable and effective therapy. Chasteberry fruit is commonly used in Europe for this condition. Given the strong placebo response noted with PMS1 and the increasing popularity and availability of herbal formulations in the United States, carefully controlled trials are needed to assess these new treatment options.
POPULATION STUDIED: Six general medicine outpatient clinics in Germany recruited 178 women aged 18 years or older with PMS as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Exclusion criteria included psychotherapy, any serious medical condition, pregnancy, breast-feeding, inadequate contraception, alcohol or drug dependence, hypersensitivity to chasteberry, fever, pituitary disease, or use of sex hormones other than oral contraceptives. The treatment groups did not differ significantly in terms of age (mean=36 years), weight, cycle characteristics, or initial assessments of severity.
STUDY DESIGN AND VALIDITY: In this prospective randomized double-blind placebo-controlled trial, participants received either a chasteberry (ZE 440) 20-mg tablet standardized for casticin (one of the presumed active principles) or matching placebo once daily. The authors assessed efficacy by comparing validated self-assessment scales at baseline (beginning of first menstrual cycle) and at the end of the third cycle. Tolerability was assessed using side effects reported at the last study visit, rather than by recording in a daily diary.
OUTCOMES MEASURED: The primary outcome was the change from baseline to end point in a combined score of 6 self-assessment items rated on a visual analog scale (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast fullness). The secondary outcomes included each of the 6 items independently, 3 global assessment items (corroborated by physicians), and the responder rate, defined as 50% or more reduction in self-assessed symptoms from baseline.
RESULTS: Compared with placebo, patients who received chasteberry had a significant improvement in the combined symptom score (P <.001). In 5 of the 6 self-assessment items (irritability, mood alteration, anger, headache, and breast fullness), chasteberry was more effective than placebo (P <.01), with “other symptoms including bloating” being unaffected by treatment. All 3 global assessment items significantly favored the treated group, as did the responder rate (52% vs 24%, no statistical analysis presented). These results remained unchanged by subgroup analyses that excluded women taking oral contraceptives and included the 8 women initially screened but without postbaseline values who were removed from the initial intention-to-treat population. Side effect rates were similar in the 2 groups; all were mild, and none led to discontinuation.
The formulation of chasteberry used in this appropriately designed study was well tolerated and more effective than placebo in decreasing symptoms of PMS. Most symptoms of PMS significantly improved with active treatment, and slightly more than half the women taking this herb experienced a substantial (>50%) decrease in overall symptoms. Because of reduced Food and Drug Administration oversight of the manufacturing of herbal medicines in the United States, we cannot be certain that our patients have access to chasteberry extract similar to the one used in this study. If such a product can be found, it can be recommended as one of the initial treatments for this common and troublesome condition.
Are zinc acetate lozenges effective in decreasing the duration of symptoms of the common cold?
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).
The zinc acetate lozenge formulation used in this well-designed study was more effective than placebo in decreasing the duration and severity of cold symptoms, especially cough and nasal discharge. However, twice as many zinc-treated subjects correctly identified their lozenges at the end of the study, suggesting that blinding may not have been completely maintained. Also, the 2 groups differed with regard to potential confounders (ie, smoking status and allergy history). Despite these shortcomings, this study adds to the growing evidence that certain zinc lozenge formulations shorten the duration and decrease the severity of cold symptoms.
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).
The zinc acetate lozenge formulation used in this well-designed study was more effective than placebo in decreasing the duration and severity of cold symptoms, especially cough and nasal discharge. However, twice as many zinc-treated subjects correctly identified their lozenges at the end of the study, suggesting that blinding may not have been completely maintained. Also, the 2 groups differed with regard to potential confounders (ie, smoking status and allergy history). Despite these shortcomings, this study adds to the growing evidence that certain zinc lozenge formulations shorten the duration and decrease the severity of cold symptoms.
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).
The zinc acetate lozenge formulation used in this well-designed study was more effective than placebo in decreasing the duration and severity of cold symptoms, especially cough and nasal discharge. However, twice as many zinc-treated subjects correctly identified their lozenges at the end of the study, suggesting that blinding may not have been completely maintained. Also, the 2 groups differed with regard to potential confounders (ie, smoking status and allergy history). Despite these shortcomings, this study adds to the growing evidence that certain zinc lozenge formulations shorten the duration and decrease the severity of cold symptoms.
Is losartan superior to captopril in reducing all-cause mortality in elderly patients with symptomatic heart failure?
BACKGROUND: Because of their beneficial effects on mortality risk and functional status, angiotensin-converting-enzyme (ACE) inhibitors should be prescribed for all patients with heart failure and systolic left ventricular dysfunction unless specific contraindications exist. However, some physicians do not prescribe them because of fear of adverse effects. Angiotensin II type 1 receptor blockers (AT1RBs) may be better tolerated than ACE inhibitors. A secondary analysis of 49 deaths in the original Evaluation of Losartan in the Elderly (ELITE) study, in which the primary end point was the effect of treatment on renal function, showed an unexpected survival benefit for the AT1RB losartan over captopril, an ACE inhibitor. ELITE II was a larger trial designed to confirm whether losartan is superior to captopril in reducing all-cause mortality in elderly heart failure patients.
POPULATION STUDIED: The study included 3152 patients aged 60 years or older with New York Heart Association class II to IV heart failure and an ejection fraction of 40% or less. Most of the patients recruited from the 289 outpatient centers in 46 countries were white men aged older than 65 years who had never received an ACE inhibitor or an AT1RB. Exclusion criteria included previous intolerance or contraindication to either the study drug, systolic blood pressure greater than 90 mm Hg, uncontrolled hypertension, obstructive valvular heart disease, recent cardiac procedure or event, anticipated cardiac surgery, or recent cerebrovascular event.
STUDY DESIGN AND VALIDITY: This study was a prospective randomized double-blind trial funded by the manufacturer of losartan. Designed as an event-driven superiority trial, the study had 90% power to detect a relative 25% difference in all-cause mortality between treatments. At each study center, randomization was stratified on the basis of use of b-blockers. After a single-blind run-in period of 1 to 28 days, 1578 patients were allocated to losartan (12.5 mg titrated to a maximum of 50 mg once daily) and 1574 to captopril (12.5 mg titrated to a maximum of 50 mg 3 times daily). Clinical assessments were done weekly during dose titration and then every 4 months. Periodic laboratory assessments were also performed. The appropriate study design and intention-to-treat analysis were used for this efficacy trial. Neither the patients, those assessing clinical outcomes, nor the drug safety monitoring committee were aware of treatment status. Concealed allocation to treatment group at each study site was assured through central block randomization. The results are only applicable to elderly patients.
OUTCOMES MEASURED: The primary outcome was all-cause mortality, and the secondary end point was the composite of sudden cardiac death or resuscitated cardiac arrest.
RESULTS: Treatment groups were well matched demographically and for confounding variables that might affect response to treatment. Only 1 patient from each group was lost to follow-up during a median follow-up period of 18 months. A total of 280 deaths (17.5%) occurred in the losartan group compared with 250 (15.9%) in the captopril group, with an annual mortality rate of 11.7% and 10.4%, respectively (hazard ratio=1.13; 95.7% confidence interval, 0.95-1.35; P=.16). Neither of these differences was statistically significant, but power may have been an issue. Similarly, there was no significant difference in the composite of sudden death or resuscitated arrests (9.0% vs 7.3%). Fewer patients in the losartan group (excluding those who died) discontinued treatment because of side effects (9.7% vs 14.7%, P <.001).
Clinicians should continue to prescribe ACE inhibitors as initial treatment for elderly patients with symptomatic heart failure. Losartan was clearly not superior (or even equivalent) to captopril in reducing all-cause mortality and should not be used as first-line therapy for these patients.
BACKGROUND: Because of their beneficial effects on mortality risk and functional status, angiotensin-converting-enzyme (ACE) inhibitors should be prescribed for all patients with heart failure and systolic left ventricular dysfunction unless specific contraindications exist. However, some physicians do not prescribe them because of fear of adverse effects. Angiotensin II type 1 receptor blockers (AT1RBs) may be better tolerated than ACE inhibitors. A secondary analysis of 49 deaths in the original Evaluation of Losartan in the Elderly (ELITE) study, in which the primary end point was the effect of treatment on renal function, showed an unexpected survival benefit for the AT1RB losartan over captopril, an ACE inhibitor. ELITE II was a larger trial designed to confirm whether losartan is superior to captopril in reducing all-cause mortality in elderly heart failure patients.
POPULATION STUDIED: The study included 3152 patients aged 60 years or older with New York Heart Association class II to IV heart failure and an ejection fraction of 40% or less. Most of the patients recruited from the 289 outpatient centers in 46 countries were white men aged older than 65 years who had never received an ACE inhibitor or an AT1RB. Exclusion criteria included previous intolerance or contraindication to either the study drug, systolic blood pressure greater than 90 mm Hg, uncontrolled hypertension, obstructive valvular heart disease, recent cardiac procedure or event, anticipated cardiac surgery, or recent cerebrovascular event.
STUDY DESIGN AND VALIDITY: This study was a prospective randomized double-blind trial funded by the manufacturer of losartan. Designed as an event-driven superiority trial, the study had 90% power to detect a relative 25% difference in all-cause mortality between treatments. At each study center, randomization was stratified on the basis of use of b-blockers. After a single-blind run-in period of 1 to 28 days, 1578 patients were allocated to losartan (12.5 mg titrated to a maximum of 50 mg once daily) and 1574 to captopril (12.5 mg titrated to a maximum of 50 mg 3 times daily). Clinical assessments were done weekly during dose titration and then every 4 months. Periodic laboratory assessments were also performed. The appropriate study design and intention-to-treat analysis were used for this efficacy trial. Neither the patients, those assessing clinical outcomes, nor the drug safety monitoring committee were aware of treatment status. Concealed allocation to treatment group at each study site was assured through central block randomization. The results are only applicable to elderly patients.
OUTCOMES MEASURED: The primary outcome was all-cause mortality, and the secondary end point was the composite of sudden cardiac death or resuscitated cardiac arrest.
RESULTS: Treatment groups were well matched demographically and for confounding variables that might affect response to treatment. Only 1 patient from each group was lost to follow-up during a median follow-up period of 18 months. A total of 280 deaths (17.5%) occurred in the losartan group compared with 250 (15.9%) in the captopril group, with an annual mortality rate of 11.7% and 10.4%, respectively (hazard ratio=1.13; 95.7% confidence interval, 0.95-1.35; P=.16). Neither of these differences was statistically significant, but power may have been an issue. Similarly, there was no significant difference in the composite of sudden death or resuscitated arrests (9.0% vs 7.3%). Fewer patients in the losartan group (excluding those who died) discontinued treatment because of side effects (9.7% vs 14.7%, P <.001).
Clinicians should continue to prescribe ACE inhibitors as initial treatment for elderly patients with symptomatic heart failure. Losartan was clearly not superior (or even equivalent) to captopril in reducing all-cause mortality and should not be used as first-line therapy for these patients.
BACKGROUND: Because of their beneficial effects on mortality risk and functional status, angiotensin-converting-enzyme (ACE) inhibitors should be prescribed for all patients with heart failure and systolic left ventricular dysfunction unless specific contraindications exist. However, some physicians do not prescribe them because of fear of adverse effects. Angiotensin II type 1 receptor blockers (AT1RBs) may be better tolerated than ACE inhibitors. A secondary analysis of 49 deaths in the original Evaluation of Losartan in the Elderly (ELITE) study, in which the primary end point was the effect of treatment on renal function, showed an unexpected survival benefit for the AT1RB losartan over captopril, an ACE inhibitor. ELITE II was a larger trial designed to confirm whether losartan is superior to captopril in reducing all-cause mortality in elderly heart failure patients.
POPULATION STUDIED: The study included 3152 patients aged 60 years or older with New York Heart Association class II to IV heart failure and an ejection fraction of 40% or less. Most of the patients recruited from the 289 outpatient centers in 46 countries were white men aged older than 65 years who had never received an ACE inhibitor or an AT1RB. Exclusion criteria included previous intolerance or contraindication to either the study drug, systolic blood pressure greater than 90 mm Hg, uncontrolled hypertension, obstructive valvular heart disease, recent cardiac procedure or event, anticipated cardiac surgery, or recent cerebrovascular event.
STUDY DESIGN AND VALIDITY: This study was a prospective randomized double-blind trial funded by the manufacturer of losartan. Designed as an event-driven superiority trial, the study had 90% power to detect a relative 25% difference in all-cause mortality between treatments. At each study center, randomization was stratified on the basis of use of b-blockers. After a single-blind run-in period of 1 to 28 days, 1578 patients were allocated to losartan (12.5 mg titrated to a maximum of 50 mg once daily) and 1574 to captopril (12.5 mg titrated to a maximum of 50 mg 3 times daily). Clinical assessments were done weekly during dose titration and then every 4 months. Periodic laboratory assessments were also performed. The appropriate study design and intention-to-treat analysis were used for this efficacy trial. Neither the patients, those assessing clinical outcomes, nor the drug safety monitoring committee were aware of treatment status. Concealed allocation to treatment group at each study site was assured through central block randomization. The results are only applicable to elderly patients.
OUTCOMES MEASURED: The primary outcome was all-cause mortality, and the secondary end point was the composite of sudden cardiac death or resuscitated cardiac arrest.
RESULTS: Treatment groups were well matched demographically and for confounding variables that might affect response to treatment. Only 1 patient from each group was lost to follow-up during a median follow-up period of 18 months. A total of 280 deaths (17.5%) occurred in the losartan group compared with 250 (15.9%) in the captopril group, with an annual mortality rate of 11.7% and 10.4%, respectively (hazard ratio=1.13; 95.7% confidence interval, 0.95-1.35; P=.16). Neither of these differences was statistically significant, but power may have been an issue. Similarly, there was no significant difference in the composite of sudden death or resuscitated arrests (9.0% vs 7.3%). Fewer patients in the losartan group (excluding those who died) discontinued treatment because of side effects (9.7% vs 14.7%, P <.001).
Clinicians should continue to prescribe ACE inhibitors as initial treatment for elderly patients with symptomatic heart failure. Losartan was clearly not superior (or even equivalent) to captopril in reducing all-cause mortality and should not be used as first-line therapy for these patients.
In patients with stable persistent asthma, can lower doses of inhaled corticosteroid medication control symptoms and maintain optimal pulmonary function as well as high doses?
BACKGROUND: In patients with chronic asthma, inflammation caused by numerous stimuli leads to recurrent symptoms, variable airflow obstruction, and bronchial hyperresponsiveness. Effective long-term control of persistent asthma requires daily administration of an anti-inflammatory agent, preferably an inhaled corticosteroid. Although inhaled steroids are generally well tolerated and safe, the lowest effective dose should be used to reduce the potential for adverse effects.1
POPULATION STUDIED: The investigators enrolled 220 adult patients with perennial asthma from 14 outpatient clinics in Italy. Patients in this study had to be using an inhaled corticosteroid and an inhaled b2-agonist daily, had a baseline forced expiratory volume in 1 second between 50% and 90% predicted, and had symptoms present that interfered with normal daily activity during the previous 2 weeks. Patients were not included if they required systemic corticosteroids within the past month or used more than 1000 μg per day of inhaled beclomethasone dipropionate.
STUDY DESIGN AND VALIDITY: The appropriate study design was used for this article about therapy. It was a prospective randomized double-blind trial funded by the manufacturer of budesonide (available in the United States as Pulmicort). Following a 2-week observation period to establish asthma severity, all patients were treated with high-dose (800 μg twice daily) inhaled budesonide for 1 month. Patients were then randomized to receive either 400 μg (standard dose) or 100 μg (low dose) of budesonide twice daily for 6 months. The high-dose group received a placebo inhaler for use during exacerbations. The low-dose group was further divided to receive either a placebo inhaler or budesonide 200 μg 4 times daily during exacerbations. Exacerbations were identified using daily peak flow measurements to trigger the short-term use of either higher doses of inhaled budesonide or the placebo inhaler. Patients were assessed monthly and were asked to maintain a daily record of asthma symptoms, exacerbations, peak flow values, and use of b2-agonists. The patients and those assessing response to therapy were not aware of the budesonide dose. Concealed allocation to treatment group at each study site was assured through central randomization. Eighty percent of the enrolled patients completed the study, and all withdrawals were explained. Only adults (18 years and older) were studied, and the results may not be applicable to children.
OUTCOMES MEASURED: Both patient-oriented outcomes (symptom control and number of exacerbations) and disease-oriented outcomes (pulmonary function) were used to assess treatment response.
RESULTS: Of 220 enrolled patients, 213 were randomized to different doses of budesonide. The results for 209 of these (4 withdrew just after randomization) were analyzed appropriately by intention to treat. Treatment groups were well matched demographically and for confounding factors that might influence response to treatment. All patients responded well to the 4 weeks of high-dose therapy, showing progressive improvement in pulmonary function, with the majority reporting no symptoms at the end of the month. Standard-dose and low-dose budesonide controlled symptoms equally throughout the study, with no statistically significant differences reported for any symptom. Patients receiving standard-dose budesonide experienced fewer exacerbations than those receiving low-dose therapy. However, low-dose therapy patients using increased budesonide doses during exacerbations experienced significantly fewer exacerbations and fewer days of worsened symptoms than those continuing on low doses. The low-dose group using as-needed higher doses did not differ from the standard-dose group with respect to the number of days with exacerbations.
For adults with chronic asthma, a regimen of low-dose inhaled budesonide plus higher doses during exacerbations was as effective as continuous standard doses for controlling symptoms and minimizing exacerbations. For patients willing to perform daily peak flow monitoring to allow early treatment of mild exacerbations with increased doses of inhaled corticosteroid medication, this approach can result in good long-term asthma control with lower doses of inhaled corticosteroids.
BACKGROUND: In patients with chronic asthma, inflammation caused by numerous stimuli leads to recurrent symptoms, variable airflow obstruction, and bronchial hyperresponsiveness. Effective long-term control of persistent asthma requires daily administration of an anti-inflammatory agent, preferably an inhaled corticosteroid. Although inhaled steroids are generally well tolerated and safe, the lowest effective dose should be used to reduce the potential for adverse effects.1
POPULATION STUDIED: The investigators enrolled 220 adult patients with perennial asthma from 14 outpatient clinics in Italy. Patients in this study had to be using an inhaled corticosteroid and an inhaled b2-agonist daily, had a baseline forced expiratory volume in 1 second between 50% and 90% predicted, and had symptoms present that interfered with normal daily activity during the previous 2 weeks. Patients were not included if they required systemic corticosteroids within the past month or used more than 1000 μg per day of inhaled beclomethasone dipropionate.
STUDY DESIGN AND VALIDITY: The appropriate study design was used for this article about therapy. It was a prospective randomized double-blind trial funded by the manufacturer of budesonide (available in the United States as Pulmicort). Following a 2-week observation period to establish asthma severity, all patients were treated with high-dose (800 μg twice daily) inhaled budesonide for 1 month. Patients were then randomized to receive either 400 μg (standard dose) or 100 μg (low dose) of budesonide twice daily for 6 months. The high-dose group received a placebo inhaler for use during exacerbations. The low-dose group was further divided to receive either a placebo inhaler or budesonide 200 μg 4 times daily during exacerbations. Exacerbations were identified using daily peak flow measurements to trigger the short-term use of either higher doses of inhaled budesonide or the placebo inhaler. Patients were assessed monthly and were asked to maintain a daily record of asthma symptoms, exacerbations, peak flow values, and use of b2-agonists. The patients and those assessing response to therapy were not aware of the budesonide dose. Concealed allocation to treatment group at each study site was assured through central randomization. Eighty percent of the enrolled patients completed the study, and all withdrawals were explained. Only adults (18 years and older) were studied, and the results may not be applicable to children.
OUTCOMES MEASURED: Both patient-oriented outcomes (symptom control and number of exacerbations) and disease-oriented outcomes (pulmonary function) were used to assess treatment response.
RESULTS: Of 220 enrolled patients, 213 were randomized to different doses of budesonide. The results for 209 of these (4 withdrew just after randomization) were analyzed appropriately by intention to treat. Treatment groups were well matched demographically and for confounding factors that might influence response to treatment. All patients responded well to the 4 weeks of high-dose therapy, showing progressive improvement in pulmonary function, with the majority reporting no symptoms at the end of the month. Standard-dose and low-dose budesonide controlled symptoms equally throughout the study, with no statistically significant differences reported for any symptom. Patients receiving standard-dose budesonide experienced fewer exacerbations than those receiving low-dose therapy. However, low-dose therapy patients using increased budesonide doses during exacerbations experienced significantly fewer exacerbations and fewer days of worsened symptoms than those continuing on low doses. The low-dose group using as-needed higher doses did not differ from the standard-dose group with respect to the number of days with exacerbations.
For adults with chronic asthma, a regimen of low-dose inhaled budesonide plus higher doses during exacerbations was as effective as continuous standard doses for controlling symptoms and minimizing exacerbations. For patients willing to perform daily peak flow monitoring to allow early treatment of mild exacerbations with increased doses of inhaled corticosteroid medication, this approach can result in good long-term asthma control with lower doses of inhaled corticosteroids.
BACKGROUND: In patients with chronic asthma, inflammation caused by numerous stimuli leads to recurrent symptoms, variable airflow obstruction, and bronchial hyperresponsiveness. Effective long-term control of persistent asthma requires daily administration of an anti-inflammatory agent, preferably an inhaled corticosteroid. Although inhaled steroids are generally well tolerated and safe, the lowest effective dose should be used to reduce the potential for adverse effects.1
POPULATION STUDIED: The investigators enrolled 220 adult patients with perennial asthma from 14 outpatient clinics in Italy. Patients in this study had to be using an inhaled corticosteroid and an inhaled b2-agonist daily, had a baseline forced expiratory volume in 1 second between 50% and 90% predicted, and had symptoms present that interfered with normal daily activity during the previous 2 weeks. Patients were not included if they required systemic corticosteroids within the past month or used more than 1000 μg per day of inhaled beclomethasone dipropionate.
STUDY DESIGN AND VALIDITY: The appropriate study design was used for this article about therapy. It was a prospective randomized double-blind trial funded by the manufacturer of budesonide (available in the United States as Pulmicort). Following a 2-week observation period to establish asthma severity, all patients were treated with high-dose (800 μg twice daily) inhaled budesonide for 1 month. Patients were then randomized to receive either 400 μg (standard dose) or 100 μg (low dose) of budesonide twice daily for 6 months. The high-dose group received a placebo inhaler for use during exacerbations. The low-dose group was further divided to receive either a placebo inhaler or budesonide 200 μg 4 times daily during exacerbations. Exacerbations were identified using daily peak flow measurements to trigger the short-term use of either higher doses of inhaled budesonide or the placebo inhaler. Patients were assessed monthly and were asked to maintain a daily record of asthma symptoms, exacerbations, peak flow values, and use of b2-agonists. The patients and those assessing response to therapy were not aware of the budesonide dose. Concealed allocation to treatment group at each study site was assured through central randomization. Eighty percent of the enrolled patients completed the study, and all withdrawals were explained. Only adults (18 years and older) were studied, and the results may not be applicable to children.
OUTCOMES MEASURED: Both patient-oriented outcomes (symptom control and number of exacerbations) and disease-oriented outcomes (pulmonary function) were used to assess treatment response.
RESULTS: Of 220 enrolled patients, 213 were randomized to different doses of budesonide. The results for 209 of these (4 withdrew just after randomization) were analyzed appropriately by intention to treat. Treatment groups were well matched demographically and for confounding factors that might influence response to treatment. All patients responded well to the 4 weeks of high-dose therapy, showing progressive improvement in pulmonary function, with the majority reporting no symptoms at the end of the month. Standard-dose and low-dose budesonide controlled symptoms equally throughout the study, with no statistically significant differences reported for any symptom. Patients receiving standard-dose budesonide experienced fewer exacerbations than those receiving low-dose therapy. However, low-dose therapy patients using increased budesonide doses during exacerbations experienced significantly fewer exacerbations and fewer days of worsened symptoms than those continuing on low doses. The low-dose group using as-needed higher doses did not differ from the standard-dose group with respect to the number of days with exacerbations.
For adults with chronic asthma, a regimen of low-dose inhaled budesonide plus higher doses during exacerbations was as effective as continuous standard doses for controlling symptoms and minimizing exacerbations. For patients willing to perform daily peak flow monitoring to allow early treatment of mild exacerbations with increased doses of inhaled corticosteroid medication, this approach can result in good long-term asthma control with lower doses of inhaled corticosteroids.
Corticosteroids for the Treatment of Croup
CLINICAL QUESTION: Are corticosteroids effective in the treatment of croup?
BACKGROUND: Croup (laryngotracheobronchitis) is a common upper respiratory illness in children. Although it is often self-limiting, croup can cause significant morbidity and be costly to health care systems because of frequent visits to physicians or emergency departments and hospitalizations. The customary therapy of humidified air has only anecdotal benefits, and the evidence for racemic epinephrine shows only temporary relief at best.
POPULATION STUDIED: The 24 trials in this analysis included children 4 months to 12 years of age (mean ages ranged from 13 to 45 months). The authors of 14 trials studied inpatients (1375 patients), and 10 were conducted in emergency departments (846 patients).
STUDY DESIGN AND VALIDITY: This was a well-executed meta-analysis in which the authors combined the results of 24 randomized controlled trials that examined the effectiveness of corticosteroids for children with croup. Ninety-seven studies were initially identified by searching MEDLINE (1966 to 1997), EMBASE (1974 to 1997), and The Cochrane Controlled Trials Register of The Cochrane Library, as well as by corresponding with the authors of trials published in the previous 5 years. Studies were selected if 2 reviewers independently judged that these randomized controlled trials compared a corticosteroid with placebo or an active control and used a clinically important outcome. Seventy-three trials were excluded from analysis for appropriate reasons. Two independent reviewers blinded to author and study location assessed the quality of included trials using a validated 5-point scale. Systemic dexamethasone (Decadron) and nebulized budesonide (Pulmicort) were the most commonly studied drugs.
OUTCOMES MEASURED: Scores on scales measuring severity of croup symptoms, use of additional interventions, length of stay in the emergency department or hospital, and hospitalization rates were the main outcomes evaluated in this analysis. The 17-point Westley Clinical Croup Scale was the most frequently used outcome measure (13 studies). Other nonvalidated scoring systems were used in 5 studies, while 6 studies did not report a clinical croup score. Trial effect sizes were used in the pooled analyses because of inconsistency in the reporting of croup scores.
RESULTS: A significantly greater decrease in croup symptoms was noted after 6 and 12 hours of treatment with corticosteroids compared with treatment with placebo or a nonsteroid control. At 6 hours, this difference resulted in an average 15% improvement in symptom scores (95% confidence interval [CI], 2%-28%) with a number needed to treat (NNT) of 7. At 12 hours, the difference was 21% (95% CI, 9%-33%) with an NNT of 5.
In this well-executed meta-analysis corticosteroids were shown to have a small but clinically important beneficial effect on croup symptoms. The most frequently studied agents were inhaled budesonide and systemic dexamethasone. The authors were unable to compare different corticosteroids, doses, and routes of administration. These results are similar to those of a meta-analysis performed 10 years ago.1 Treatment of 5 children with croup with steroids will result in symptom improvement in one of them within 12 hours (NNT = 5). Additionally, use of these drugs decreases the need for additional interventions and the length of stay in the emergency department or hospital. The size of the effect is small and is perhaps overestimated. However, the low cost and low risk of these drugs make them worth a try in the acute management of this common problem.
CLINICAL QUESTION: Are corticosteroids effective in the treatment of croup?
BACKGROUND: Croup (laryngotracheobronchitis) is a common upper respiratory illness in children. Although it is often self-limiting, croup can cause significant morbidity and be costly to health care systems because of frequent visits to physicians or emergency departments and hospitalizations. The customary therapy of humidified air has only anecdotal benefits, and the evidence for racemic epinephrine shows only temporary relief at best.
POPULATION STUDIED: The 24 trials in this analysis included children 4 months to 12 years of age (mean ages ranged from 13 to 45 months). The authors of 14 trials studied inpatients (1375 patients), and 10 were conducted in emergency departments (846 patients).
STUDY DESIGN AND VALIDITY: This was a well-executed meta-analysis in which the authors combined the results of 24 randomized controlled trials that examined the effectiveness of corticosteroids for children with croup. Ninety-seven studies were initially identified by searching MEDLINE (1966 to 1997), EMBASE (1974 to 1997), and The Cochrane Controlled Trials Register of The Cochrane Library, as well as by corresponding with the authors of trials published in the previous 5 years. Studies were selected if 2 reviewers independently judged that these randomized controlled trials compared a corticosteroid with placebo or an active control and used a clinically important outcome. Seventy-three trials were excluded from analysis for appropriate reasons. Two independent reviewers blinded to author and study location assessed the quality of included trials using a validated 5-point scale. Systemic dexamethasone (Decadron) and nebulized budesonide (Pulmicort) were the most commonly studied drugs.
OUTCOMES MEASURED: Scores on scales measuring severity of croup symptoms, use of additional interventions, length of stay in the emergency department or hospital, and hospitalization rates were the main outcomes evaluated in this analysis. The 17-point Westley Clinical Croup Scale was the most frequently used outcome measure (13 studies). Other nonvalidated scoring systems were used in 5 studies, while 6 studies did not report a clinical croup score. Trial effect sizes were used in the pooled analyses because of inconsistency in the reporting of croup scores.
RESULTS: A significantly greater decrease in croup symptoms was noted after 6 and 12 hours of treatment with corticosteroids compared with treatment with placebo or a nonsteroid control. At 6 hours, this difference resulted in an average 15% improvement in symptom scores (95% confidence interval [CI], 2%-28%) with a number needed to treat (NNT) of 7. At 12 hours, the difference was 21% (95% CI, 9%-33%) with an NNT of 5.
In this well-executed meta-analysis corticosteroids were shown to have a small but clinically important beneficial effect on croup symptoms. The most frequently studied agents were inhaled budesonide and systemic dexamethasone. The authors were unable to compare different corticosteroids, doses, and routes of administration. These results are similar to those of a meta-analysis performed 10 years ago.1 Treatment of 5 children with croup with steroids will result in symptom improvement in one of them within 12 hours (NNT = 5). Additionally, use of these drugs decreases the need for additional interventions and the length of stay in the emergency department or hospital. The size of the effect is small and is perhaps overestimated. However, the low cost and low risk of these drugs make them worth a try in the acute management of this common problem.
CLINICAL QUESTION: Are corticosteroids effective in the treatment of croup?
BACKGROUND: Croup (laryngotracheobronchitis) is a common upper respiratory illness in children. Although it is often self-limiting, croup can cause significant morbidity and be costly to health care systems because of frequent visits to physicians or emergency departments and hospitalizations. The customary therapy of humidified air has only anecdotal benefits, and the evidence for racemic epinephrine shows only temporary relief at best.
POPULATION STUDIED: The 24 trials in this analysis included children 4 months to 12 years of age (mean ages ranged from 13 to 45 months). The authors of 14 trials studied inpatients (1375 patients), and 10 were conducted in emergency departments (846 patients).
STUDY DESIGN AND VALIDITY: This was a well-executed meta-analysis in which the authors combined the results of 24 randomized controlled trials that examined the effectiveness of corticosteroids for children with croup. Ninety-seven studies were initially identified by searching MEDLINE (1966 to 1997), EMBASE (1974 to 1997), and The Cochrane Controlled Trials Register of The Cochrane Library, as well as by corresponding with the authors of trials published in the previous 5 years. Studies were selected if 2 reviewers independently judged that these randomized controlled trials compared a corticosteroid with placebo or an active control and used a clinically important outcome. Seventy-three trials were excluded from analysis for appropriate reasons. Two independent reviewers blinded to author and study location assessed the quality of included trials using a validated 5-point scale. Systemic dexamethasone (Decadron) and nebulized budesonide (Pulmicort) were the most commonly studied drugs.
OUTCOMES MEASURED: Scores on scales measuring severity of croup symptoms, use of additional interventions, length of stay in the emergency department or hospital, and hospitalization rates were the main outcomes evaluated in this analysis. The 17-point Westley Clinical Croup Scale was the most frequently used outcome measure (13 studies). Other nonvalidated scoring systems were used in 5 studies, while 6 studies did not report a clinical croup score. Trial effect sizes were used in the pooled analyses because of inconsistency in the reporting of croup scores.
RESULTS: A significantly greater decrease in croup symptoms was noted after 6 and 12 hours of treatment with corticosteroids compared with treatment with placebo or a nonsteroid control. At 6 hours, this difference resulted in an average 15% improvement in symptom scores (95% confidence interval [CI], 2%-28%) with a number needed to treat (NNT) of 7. At 12 hours, the difference was 21% (95% CI, 9%-33%) with an NNT of 5.
In this well-executed meta-analysis corticosteroids were shown to have a small but clinically important beneficial effect on croup symptoms. The most frequently studied agents were inhaled budesonide and systemic dexamethasone. The authors were unable to compare different corticosteroids, doses, and routes of administration. These results are similar to those of a meta-analysis performed 10 years ago.1 Treatment of 5 children with croup with steroids will result in symptom improvement in one of them within 12 hours (NNT = 5). Additionally, use of these drugs decreases the need for additional interventions and the length of stay in the emergency department or hospital. The size of the effect is small and is perhaps overestimated. However, the low cost and low risk of these drugs make them worth a try in the acute management of this common problem.