Q&A

ABSTRACT

BACKGROUND: Pain that occurs from perineal laceration or episiotomy during childbirth can be severe and is often undertreated. This randomized double-blind controlled trial was designed to compare the effectiveness and side effects related to 2 common analgesics used in this setting: ibuprofen and acetaminophen with codeine.

POPULATION STUDIED: The study looked at 237 women who delivered vaginally and who had either a third- or fourth-degree perineal laceration or an episiotomy. The trial took place between August 1995 and November 1996 at a tertiary-care teaching and referral center for obstetric care in Vancouver, BC, Canada. Approximately 35% of the women enrolled spoke Cantonese or Mandarin; these women were supplied with consent forms in Chinese script translated by a bilingual nurse. Women were excluded for allergy to either of the study drugs, history of drug dependence, regular use of analgesic drugs, or any medical condition known to be potentially exacerbated by opioids or nonsteroidal anti-inflammatory drugs. Women were also excluded if any major postpartum complication, including postpartum hemorrhage, had occurred. The 2 groups of women did not differ significantly in sociodemographic characteristics or in gravidity and parity. All but 4 of the 237 women enrolled completed the study. The 2 treatment groups did not differ significantly except that the ibuprofen group contained more women who had had forceps delivery.

STUDY DESIGN AND VALIDITY: This study was a randomized, double-blind trial with no placebo control. Randomization was done in blocks of 20 and stratified on the use of forceps, which were postulated to contribute significantly to postpartum pain. Women were randomized within 1 hour after delivery to receive either 400 mg ibuprofen or 600 mg acetaminophen with 60 mg codeine and 30 mg caffeine every 4 hours for 24 hours after birth. The pharmacy allocated the patients to the treatment groups. Women and their nurses were blinded. Women who did not request analgesia were not enrolled.

OUTCOMES MEASURED: The primary outcome measured was severity of pain rated on a 10-cm visual analog scale. Other outcomes evaluated were the number of doses of medication, dosing intervals, treatment failures, side effects, overall level of satisfaction, cost of treatment, and nursing time required for medication administration.

RESULTS: Both groups had similar pain ratings before taking the first dose of analgesic (rating of 3.4 for ibuprofen vs 3.3 for acetaminophen plus codeine plus caffeine) as well as number of medication doses in 24 hours (3.4 vs 3.3) and treatment failures (13.8% vs 16%). Among treatment failures, 78% occurred in women who had had forceps delivery. Subjects receiving ibuprofen experienced fewer side effects (52.4% vs 71.7%, P = .006, number needed to harm = 5.2). Overall satisfaction between the groups did not differ. Ibuprofen ($0.02/tablet) was less expensive than acetaminophen with codeine ($0.05/tablet). Because of the need for additional inventory control, the administration of each dose of the codeine combination took an average of 10 minutes, more time than the administration of ibuprofen.

ABSTRACT

BACKGROUND: Pain that occurs from perineal laceration or episiotomy during childbirth can be severe and is often undertreated. This randomized double-blind controlled trial was designed to compare the effectiveness and side effects related to 2 common analgesics used in this setting: ibuprofen and acetaminophen with codeine.

POPULATION STUDIED: The study looked at 237 women who delivered vaginally and who had either a third- or fourth-degree perineal laceration or an episiotomy. The trial took place between August 1995 and November 1996 at a tertiary-care teaching and referral center for obstetric care in Vancouver, BC, Canada. Approximately 35% of the women enrolled spoke Cantonese or Mandarin; these women were supplied with consent forms in Chinese script translated by a bilingual nurse. Women were excluded for allergy to either of the study drugs, history of drug dependence, regular use of analgesic drugs, or any medical condition known to be potentially exacerbated by opioids or nonsteroidal anti-inflammatory drugs. Women were also excluded if any major postpartum complication, including postpartum hemorrhage, had occurred. The 2 groups of women did not differ significantly in sociodemographic characteristics or in gravidity and parity. All but 4 of the 237 women enrolled completed the study. The 2 treatment groups did not differ significantly except that the ibuprofen group contained more women who had had forceps delivery.

STUDY DESIGN AND VALIDITY: This study was a randomized, double-blind trial with no placebo control. Randomization was done in blocks of 20 and stratified on the use of forceps, which were postulated to contribute significantly to postpartum pain. Women were randomized within 1 hour after delivery to receive either 400 mg ibuprofen or 600 mg acetaminophen with 60 mg codeine and 30 mg caffeine every 4 hours for 24 hours after birth. The pharmacy allocated the patients to the treatment groups. Women and their nurses were blinded. Women who did not request analgesia were not enrolled.

OUTCOMES MEASURED: The primary outcome measured was severity of pain rated on a 10-cm visual analog scale. Other outcomes evaluated were the number of doses of medication, dosing intervals, treatment failures, side effects, overall level of satisfaction, cost of treatment, and nursing time required for medication administration.

RESULTS: Both groups had similar pain ratings before taking the first dose of analgesic (rating of 3.4 for ibuprofen vs 3.3 for acetaminophen plus codeine plus caffeine) as well as number of medication doses in 24 hours (3.4 vs 3.3) and treatment failures (13.8% vs 16%). Among treatment failures, 78% occurred in women who had had forceps delivery. Subjects receiving ibuprofen experienced fewer side effects (52.4% vs 71.7%, P = .006, number needed to harm = 5.2). Overall satisfaction between the groups did not differ. Ibuprofen ($0.02/tablet) was less expensive than acetaminophen with codeine ($0.05/tablet). Because of the need for additional inventory control, the administration of each dose of the codeine combination took an average of 10 minutes, more time than the administration of ibuprofen.

ABSTRACT

BACKGROUND: Pain that occurs from perineal laceration or episiotomy during childbirth can be severe and is often undertreated. This randomized double-blind controlled trial was designed to compare the effectiveness and side effects related to 2 common analgesics used in this setting: ibuprofen and acetaminophen with codeine.

POPULATION STUDIED: The study looked at 237 women who delivered vaginally and who had either a third- or fourth-degree perineal laceration or an episiotomy. The trial took place between August 1995 and November 1996 at a tertiary-care teaching and referral center for obstetric care in Vancouver, BC, Canada. Approximately 35% of the women enrolled spoke Cantonese or Mandarin; these women were supplied with consent forms in Chinese script translated by a bilingual nurse. Women were excluded for allergy to either of the study drugs, history of drug dependence, regular use of analgesic drugs, or any medical condition known to be potentially exacerbated by opioids or nonsteroidal anti-inflammatory drugs. Women were also excluded if any major postpartum complication, including postpartum hemorrhage, had occurred. The 2 groups of women did not differ significantly in sociodemographic characteristics or in gravidity and parity. All but 4 of the 237 women enrolled completed the study. The 2 treatment groups did not differ significantly except that the ibuprofen group contained more women who had had forceps delivery.

STUDY DESIGN AND VALIDITY: This study was a randomized, double-blind trial with no placebo control. Randomization was done in blocks of 20 and stratified on the use of forceps, which were postulated to contribute significantly to postpartum pain. Women were randomized within 1 hour after delivery to receive either 400 mg ibuprofen or 600 mg acetaminophen with 60 mg codeine and 30 mg caffeine every 4 hours for 24 hours after birth. The pharmacy allocated the patients to the treatment groups. Women and their nurses were blinded. Women who did not request analgesia were not enrolled.

OUTCOMES MEASURED: The primary outcome measured was severity of pain rated on a 10-cm visual analog scale. Other outcomes evaluated were the number of doses of medication, dosing intervals, treatment failures, side effects, overall level of satisfaction, cost of treatment, and nursing time required for medication administration.

RESULTS: Both groups had similar pain ratings before taking the first dose of analgesic (rating of 3.4 for ibuprofen vs 3.3 for acetaminophen plus codeine plus caffeine) as well as number of medication doses in 24 hours (3.4 vs 3.3) and treatment failures (13.8% vs 16%). Among treatment failures, 78% occurred in women who had had forceps delivery. Subjects receiving ibuprofen experienced fewer side effects (52.4% vs 71.7%, P = .006, number needed to harm = 5.2). Overall satisfaction between the groups did not differ. Ibuprofen ($0.02/tablet) was less expensive than acetaminophen with codeine ($0.05/tablet). Because of the need for additional inventory control, the administration of each dose of the codeine combination took an average of 10 minutes, more time than the administration of ibuprofen.

ABSTRACT

BACKGROUND: Because strong evidence supports the association between cervical length and preterm delivery and perinatal morbidity, transvaginal ultrasound (TVUS) has been used to identify patients with premature cervical change who may benefit from therapeutic cerclage placement. Observational studies report conflicting results regarding the benefits of therapeutic cerclage. Few randomized trials regarding the efficacy of cerclage therapy have been reported.

POPULATION STUDIED: This study enrolled 113 women from an urban outpatient perinatal testing center that had cervical changes identified by TVUS during the second trimester of pregnancy. Specific changes were dilation of the internal os and either (1) prolapse of membranes of at least 25% of the total cervical length or (2) a distal cervical length of less than 2.5 cm. Subjects were excluded if they had membrane prolapse beyond the external os or any other contraindication to cerclage. All participants were similar with regard to age, risk factors for preterm labor, and history of preterm deliveries. However, patients in the no-cerclage group tended to have an increased rate of second-trimester deliveries (12.1 vs 27.3, P = .07).

STUDY DESIGN AND VALIDITY: This was an open randomized controlled trial. Participants with cervical changes were randomized to receive either McDonald cerclage (n = 55) or no cerclage (n = 58). Before randomization, all patients received amniocentesis, multiple urogenital cultures, indomethacin, and clindamycin. All subjects were treated identically (including serial ultrasonography and modified bed rest) after the intervention. Routine prenatal care continued and cerclage was removed at 36 weeks’ gestational age or for any of the following reasons: rupture of membranes, preterm labor refractory to tocolytic therapy, or other indication for delivery. Analysis was done by intention to treat. The authors developed a stepwise logistic regression model to analyze dependent and independent variables. It is uncertain whether allocation assignment to treatment group was concealed.

OUTCOMES MEASURED: The primary outcomes measured were gestational age at delivery and neonatal morbidity, defined as none, minimal, severe, or death. The authors analyzed a number of other variables to determine any associations with the primary outcomes but did not address cost effectiveness or patient satisfaction.

RESULTS: There were no statistical differences in the primary outcomes of gestational age at delivery of less than 34 weeks’ gestation (34.9 vs 36.2, P = .8) or perinatal morbidity, reported only as perinatal death (12.7 vs 11.9, P = .9). The regression model analysis identified preterm labor, chorioamnionitis, and abruption as significant risk factors associated with the primary outcomes.

ABSTRACT

BACKGROUND: Because strong evidence supports the association between cervical length and preterm delivery and perinatal morbidity, transvaginal ultrasound (TVUS) has been used to identify patients with premature cervical change who may benefit from therapeutic cerclage placement. Observational studies report conflicting results regarding the benefits of therapeutic cerclage. Few randomized trials regarding the efficacy of cerclage therapy have been reported.

POPULATION STUDIED: This study enrolled 113 women from an urban outpatient perinatal testing center that had cervical changes identified by TVUS during the second trimester of pregnancy. Specific changes were dilation of the internal os and either (1) prolapse of membranes of at least 25% of the total cervical length or (2) a distal cervical length of less than 2.5 cm. Subjects were excluded if they had membrane prolapse beyond the external os or any other contraindication to cerclage. All participants were similar with regard to age, risk factors for preterm labor, and history of preterm deliveries. However, patients in the no-cerclage group tended to have an increased rate of second-trimester deliveries (12.1 vs 27.3, P = .07).

STUDY DESIGN AND VALIDITY: This was an open randomized controlled trial. Participants with cervical changes were randomized to receive either McDonald cerclage (n = 55) or no cerclage (n = 58). Before randomization, all patients received amniocentesis, multiple urogenital cultures, indomethacin, and clindamycin. All subjects were treated identically (including serial ultrasonography and modified bed rest) after the intervention. Routine prenatal care continued and cerclage was removed at 36 weeks’ gestational age or for any of the following reasons: rupture of membranes, preterm labor refractory to tocolytic therapy, or other indication for delivery. Analysis was done by intention to treat. The authors developed a stepwise logistic regression model to analyze dependent and independent variables. It is uncertain whether allocation assignment to treatment group was concealed.

OUTCOMES MEASURED: The primary outcomes measured were gestational age at delivery and neonatal morbidity, defined as none, minimal, severe, or death. The authors analyzed a number of other variables to determine any associations with the primary outcomes but did not address cost effectiveness or patient satisfaction.

RESULTS: There were no statistical differences in the primary outcomes of gestational age at delivery of less than 34 weeks’ gestation (34.9 vs 36.2, P = .8) or perinatal morbidity, reported only as perinatal death (12.7 vs 11.9, P = .9). The regression model analysis identified preterm labor, chorioamnionitis, and abruption as significant risk factors associated with the primary outcomes.

ABSTRACT

BACKGROUND: Because strong evidence supports the association between cervical length and preterm delivery and perinatal morbidity, transvaginal ultrasound (TVUS) has been used to identify patients with premature cervical change who may benefit from therapeutic cerclage placement. Observational studies report conflicting results regarding the benefits of therapeutic cerclage. Few randomized trials regarding the efficacy of cerclage therapy have been reported.

POPULATION STUDIED: This study enrolled 113 women from an urban outpatient perinatal testing center that had cervical changes identified by TVUS during the second trimester of pregnancy. Specific changes were dilation of the internal os and either (1) prolapse of membranes of at least 25% of the total cervical length or (2) a distal cervical length of less than 2.5 cm. Subjects were excluded if they had membrane prolapse beyond the external os or any other contraindication to cerclage. All participants were similar with regard to age, risk factors for preterm labor, and history of preterm deliveries. However, patients in the no-cerclage group tended to have an increased rate of second-trimester deliveries (12.1 vs 27.3, P = .07).

STUDY DESIGN AND VALIDITY: This was an open randomized controlled trial. Participants with cervical changes were randomized to receive either McDonald cerclage (n = 55) or no cerclage (n = 58). Before randomization, all patients received amniocentesis, multiple urogenital cultures, indomethacin, and clindamycin. All subjects were treated identically (including serial ultrasonography and modified bed rest) after the intervention. Routine prenatal care continued and cerclage was removed at 36 weeks’ gestational age or for any of the following reasons: rupture of membranes, preterm labor refractory to tocolytic therapy, or other indication for delivery. Analysis was done by intention to treat. The authors developed a stepwise logistic regression model to analyze dependent and independent variables. It is uncertain whether allocation assignment to treatment group was concealed.

OUTCOMES MEASURED: The primary outcomes measured were gestational age at delivery and neonatal morbidity, defined as none, minimal, severe, or death. The authors analyzed a number of other variables to determine any associations with the primary outcomes but did not address cost effectiveness or patient satisfaction.

RESULTS: There were no statistical differences in the primary outcomes of gestational age at delivery of less than 34 weeks’ gestation (34.9 vs 36.2, P = .8) or perinatal morbidity, reported only as perinatal death (12.7 vs 11.9, P = .9). The regression model analysis identified preterm labor, chorioamnionitis, and abruption as significant risk factors associated with the primary outcomes.

ABSTRACT

BACKGROUND: About half of all patients with type 2 diabetes will eventually die because of a cardiovascular disease–related event. This study compared whether captopril was better than other beta blockers or diuretics at decreasing cardiovascular morbidity and mortality in the patient with diabetic hypertension.

POPULATION STUDIED: Patients were 572 diabetics enrolled in the larger captopril prevention project (Lancet 1999; 353:611-6), a study of 10,985 hypertensive patients from 536 health centers in Sweden and Finland. Subjects were male and female, aged 25 to 66 years, with primary hypertension (untreated and treated) and untreated diastolic blood pressure of at least 100 mg Hg on 2 occasions. Factors for exclusion: secondary hypertension, elevated serum creatinine levels, or conditions requiring beta blocker therapy.

STUDY DESIGN AND VALIDITY: This research was a randomized controlled trial. Neither patients nor physicians were blinded, although endpoints were assessed by a committee blinded to treatment assignment. Initial allocation to treatment group was concealed from enrolling physicians. Patients were initially randomized to receive blood pressure treatment with either captopril (up to 100 mg per day) or conventional treatment with a diuretic agent or beta blocker. Patients not achieving blood pressure control were treated at the discretion of the physician with a diuretic in the captopril group or with a combination of beta blocker and diuretic in the conventional group. A calcium channel blocker could be added as a third step in either group. The goal of therapy was diastolic blood pressure less than 90 mm Hg. Patients were evaluated for an average of 6.1 years.

OUTCOMES MEASURED: The primary outcome measured was fatal and nonfatal myocardial infarction (MI) and stroke as well as other cardiovascular deaths in patients with diabetes. Other outcomes measured were the development of other cardiac disorders and noncardiovascular effects.

RESULTS: The primary outcome of fatal and nonfatal MI and stroke, as well as that of other cardiovascular deaths, was significantly lower in the captopril-treated group than in the conventional treatment group (RR = 0.59, 95% CI 0.38-0.91, number needed to treat [NNT] = 16). Overall mortality was lower as well (RR = 0.54, 95% CI 0.31-0.95). Individually, the rates of stroke, fatal cardiovascular events, and overall mortality did not differ between the 2 groups. MI (fatal and nonfatal) was markedly less frequent in the captopril group (RR = 0.34, 95% CI 0.17-0.67, NNT = 16).

ABSTRACT

BACKGROUND: About half of all patients with type 2 diabetes will eventually die because of a cardiovascular disease–related event. This study compared whether captopril was better than other beta blockers or diuretics at decreasing cardiovascular morbidity and mortality in the patient with diabetic hypertension.

POPULATION STUDIED: Patients were 572 diabetics enrolled in the larger captopril prevention project (Lancet 1999; 353:611-6), a study of 10,985 hypertensive patients from 536 health centers in Sweden and Finland. Subjects were male and female, aged 25 to 66 years, with primary hypertension (untreated and treated) and untreated diastolic blood pressure of at least 100 mg Hg on 2 occasions. Factors for exclusion: secondary hypertension, elevated serum creatinine levels, or conditions requiring beta blocker therapy.

STUDY DESIGN AND VALIDITY: This research was a randomized controlled trial. Neither patients nor physicians were blinded, although endpoints were assessed by a committee blinded to treatment assignment. Initial allocation to treatment group was concealed from enrolling physicians. Patients were initially randomized to receive blood pressure treatment with either captopril (up to 100 mg per day) or conventional treatment with a diuretic agent or beta blocker. Patients not achieving blood pressure control were treated at the discretion of the physician with a diuretic in the captopril group or with a combination of beta blocker and diuretic in the conventional group. A calcium channel blocker could be added as a third step in either group. The goal of therapy was diastolic blood pressure less than 90 mm Hg. Patients were evaluated for an average of 6.1 years.

OUTCOMES MEASURED: The primary outcome measured was fatal and nonfatal myocardial infarction (MI) and stroke as well as other cardiovascular deaths in patients with diabetes. Other outcomes measured were the development of other cardiac disorders and noncardiovascular effects.

RESULTS: The primary outcome of fatal and nonfatal MI and stroke, as well as that of other cardiovascular deaths, was significantly lower in the captopril-treated group than in the conventional treatment group (RR = 0.59, 95% CI 0.38-0.91, number needed to treat [NNT] = 16). Overall mortality was lower as well (RR = 0.54, 95% CI 0.31-0.95). Individually, the rates of stroke, fatal cardiovascular events, and overall mortality did not differ between the 2 groups. MI (fatal and nonfatal) was markedly less frequent in the captopril group (RR = 0.34, 95% CI 0.17-0.67, NNT = 16).

ABSTRACT

BACKGROUND: About half of all patients with type 2 diabetes will eventually die because of a cardiovascular disease–related event. This study compared whether captopril was better than other beta blockers or diuretics at decreasing cardiovascular morbidity and mortality in the patient with diabetic hypertension.

POPULATION STUDIED: Patients were 572 diabetics enrolled in the larger captopril prevention project (Lancet 1999; 353:611-6), a study of 10,985 hypertensive patients from 536 health centers in Sweden and Finland. Subjects were male and female, aged 25 to 66 years, with primary hypertension (untreated and treated) and untreated diastolic blood pressure of at least 100 mg Hg on 2 occasions. Factors for exclusion: secondary hypertension, elevated serum creatinine levels, or conditions requiring beta blocker therapy.

STUDY DESIGN AND VALIDITY: This research was a randomized controlled trial. Neither patients nor physicians were blinded, although endpoints were assessed by a committee blinded to treatment assignment. Initial allocation to treatment group was concealed from enrolling physicians. Patients were initially randomized to receive blood pressure treatment with either captopril (up to 100 mg per day) or conventional treatment with a diuretic agent or beta blocker. Patients not achieving blood pressure control were treated at the discretion of the physician with a diuretic in the captopril group or with a combination of beta blocker and diuretic in the conventional group. A calcium channel blocker could be added as a third step in either group. The goal of therapy was diastolic blood pressure less than 90 mm Hg. Patients were evaluated for an average of 6.1 years.

OUTCOMES MEASURED: The primary outcome measured was fatal and nonfatal myocardial infarction (MI) and stroke as well as other cardiovascular deaths in patients with diabetes. Other outcomes measured were the development of other cardiac disorders and noncardiovascular effects.

RESULTS: The primary outcome of fatal and nonfatal MI and stroke, as well as that of other cardiovascular deaths, was significantly lower in the captopril-treated group than in the conventional treatment group (RR = 0.59, 95% CI 0.38-0.91, number needed to treat [NNT] = 16). Overall mortality was lower as well (RR = 0.54, 95% CI 0.31-0.95). Individually, the rates of stroke, fatal cardiovascular events, and overall mortality did not differ between the 2 groups. MI (fatal and nonfatal) was markedly less frequent in the captopril group (RR = 0.34, 95% CI 0.17-0.67, NNT = 16).

ABSTRACT

BACKGROUND: Six selective serotonin 5-HT_1B/1D agonists (triptans) are currently approved and available in the United States; 1 more may eventually be approved. Although clinicians need evidence of the differences in efficacy and safety of these agents to assist in their prescribing decisions, a lack of head-to-head comparison trials makes this assessment difficult. The authors performed a meta-analysis of multiple trials of oral triptans to determine their relative effectiveness in treating acute migraine.

POPULATION STUDIED: Patients eligible for the studies were aged 18 to 65 years, had moderate to severe migraine, and had pain rated on a 4-point scale (0 = no pain; 3 = most severe pain). A total of 24,000 patients from 53 clinical trials met the criteria. The authors selected 100 mg sumatriptan, the most widely prescribed agent, as the reference dose.

STUDY DESIGN AND VALIDITY: The authors performed a systematic review of published English-language trials and asked the 6 pharmaceutical companies for raw data from published and unpublished trials. Five companies provided data on 6 drugs; the makers of frovatriptan did not. The investigators included studies that (1) were randomized double-blind controlled clinical trials (placebo or active comparison); (2) treated moderate or severe migraine attacks (by International Headache Society criteria) within 8 hours of migraine onset; (3) used an oral triptan at a recommended clinical dose; and (4) evaluated the headache on the 4-point pain scale. The authors excluded 23 studies that lacked a control group, used nonrecommended dosages, or studied special populations. Of the 53 trials reviewed, 31 were placebo-controlled trials and 22 were direct-comparison trials.

OUTCOMES MEASURED: Four outcomes were measured: (1) proportion of patients with a headache response (improvement to mild or no pain 2 hours post dose); (2) sustained pain-free response (2 hours post dose and no recurrence of moderate or severe migraine 2 to 24 hours post dose); (3) consistent effect of a medication over recurrent attacks in the same person; and (4) adverse reactions.

RESULTS: In placebo trials, 100 mg sumatriptan showed a mean absolute and therapeutic gain of 59% and 29% for 2-hour headache response and 29% and 10% for sustained pain-free rate. The mean therapeutic harm rate was 13% for at least 1 adverse event, 6% for 1 central nervous system event, and 2% for 1 chest event. On average, patients obtained relief for 2 of 3 consecutive migraines. Only 80 mg eletriptan had a statistically significant advantage over 100 mg sumatriptan for therapeutic gain in 2-hour headache response (number needed to treat [NNT] = 8). For therapeutic gain in 2-hour pain-free response, both 10 mg rizatriptan (NNT = 8) and 80 mg eletriptan (NNT = 13) had a statistically significant advantage. Adverse reaction rates were similar for most triptans but lower for 2.5 mg naratriptan and 12.5 mg almotriptan.

ABSTRACT

BACKGROUND: Six selective serotonin 5-HT_1B/1D agonists (triptans) are currently approved and available in the United States; 1 more may eventually be approved. Although clinicians need evidence of the differences in efficacy and safety of these agents to assist in their prescribing decisions, a lack of head-to-head comparison trials makes this assessment difficult. The authors performed a meta-analysis of multiple trials of oral triptans to determine their relative effectiveness in treating acute migraine.

POPULATION STUDIED: Patients eligible for the studies were aged 18 to 65 years, had moderate to severe migraine, and had pain rated on a 4-point scale (0 = no pain; 3 = most severe pain). A total of 24,000 patients from 53 clinical trials met the criteria. The authors selected 100 mg sumatriptan, the most widely prescribed agent, as the reference dose.

STUDY DESIGN AND VALIDITY: The authors performed a systematic review of published English-language trials and asked the 6 pharmaceutical companies for raw data from published and unpublished trials. Five companies provided data on 6 drugs; the makers of frovatriptan did not. The investigators included studies that (1) were randomized double-blind controlled clinical trials (placebo or active comparison); (2) treated moderate or severe migraine attacks (by International Headache Society criteria) within 8 hours of migraine onset; (3) used an oral triptan at a recommended clinical dose; and (4) evaluated the headache on the 4-point pain scale. The authors excluded 23 studies that lacked a control group, used nonrecommended dosages, or studied special populations. Of the 53 trials reviewed, 31 were placebo-controlled trials and 22 were direct-comparison trials.

OUTCOMES MEASURED: Four outcomes were measured: (1) proportion of patients with a headache response (improvement to mild or no pain 2 hours post dose); (2) sustained pain-free response (2 hours post dose and no recurrence of moderate or severe migraine 2 to 24 hours post dose); (3) consistent effect of a medication over recurrent attacks in the same person; and (4) adverse reactions.

RESULTS: In placebo trials, 100 mg sumatriptan showed a mean absolute and therapeutic gain of 59% and 29% for 2-hour headache response and 29% and 10% for sustained pain-free rate. The mean therapeutic harm rate was 13% for at least 1 adverse event, 6% for 1 central nervous system event, and 2% for 1 chest event. On average, patients obtained relief for 2 of 3 consecutive migraines. Only 80 mg eletriptan had a statistically significant advantage over 100 mg sumatriptan for therapeutic gain in 2-hour headache response (number needed to treat [NNT] = 8). For therapeutic gain in 2-hour pain-free response, both 10 mg rizatriptan (NNT = 8) and 80 mg eletriptan (NNT = 13) had a statistically significant advantage. Adverse reaction rates were similar for most triptans but lower for 2.5 mg naratriptan and 12.5 mg almotriptan.

ABSTRACT

BACKGROUND: Six selective serotonin 5-HT_1B/1D agonists (triptans) are currently approved and available in the United States; 1 more may eventually be approved. Although clinicians need evidence of the differences in efficacy and safety of these agents to assist in their prescribing decisions, a lack of head-to-head comparison trials makes this assessment difficult. The authors performed a meta-analysis of multiple trials of oral triptans to determine their relative effectiveness in treating acute migraine.

POPULATION STUDIED: Patients eligible for the studies were aged 18 to 65 years, had moderate to severe migraine, and had pain rated on a 4-point scale (0 = no pain; 3 = most severe pain). A total of 24,000 patients from 53 clinical trials met the criteria. The authors selected 100 mg sumatriptan, the most widely prescribed agent, as the reference dose.

STUDY DESIGN AND VALIDITY: The authors performed a systematic review of published English-language trials and asked the 6 pharmaceutical companies for raw data from published and unpublished trials. Five companies provided data on 6 drugs; the makers of frovatriptan did not. The investigators included studies that (1) were randomized double-blind controlled clinical trials (placebo or active comparison); (2) treated moderate or severe migraine attacks (by International Headache Society criteria) within 8 hours of migraine onset; (3) used an oral triptan at a recommended clinical dose; and (4) evaluated the headache on the 4-point pain scale. The authors excluded 23 studies that lacked a control group, used nonrecommended dosages, or studied special populations. Of the 53 trials reviewed, 31 were placebo-controlled trials and 22 were direct-comparison trials.

OUTCOMES MEASURED: Four outcomes were measured: (1) proportion of patients with a headache response (improvement to mild or no pain 2 hours post dose); (2) sustained pain-free response (2 hours post dose and no recurrence of moderate or severe migraine 2 to 24 hours post dose); (3) consistent effect of a medication over recurrent attacks in the same person; and (4) adverse reactions.

RESULTS: In placebo trials, 100 mg sumatriptan showed a mean absolute and therapeutic gain of 59% and 29% for 2-hour headache response and 29% and 10% for sustained pain-free rate. The mean therapeutic harm rate was 13% for at least 1 adverse event, 6% for 1 central nervous system event, and 2% for 1 chest event. On average, patients obtained relief for 2 of 3 consecutive migraines. Only 80 mg eletriptan had a statistically significant advantage over 100 mg sumatriptan for therapeutic gain in 2-hour headache response (number needed to treat [NNT] = 8). For therapeutic gain in 2-hour pain-free response, both 10 mg rizatriptan (NNT = 8) and 80 mg eletriptan (NNT = 13) had a statistically significant advantage. Adverse reaction rates were similar for most triptans but lower for 2.5 mg naratriptan and 12.5 mg almotriptan.

ABSTRACT

BACKGROUND: Initiating warfarin in patients with atrial fibrillation at a typical loading dose of 10 mg daily for 2 days may be associated with excess anticoagulation, especially in older patients. In addition, daily monitoring associated with this regimen may be inconvenient for outpatients. Initiating warfarin at 5 mg daily may produce more consistent anticoagulation and eliminate the need for daily monitoring. The investigators tested whether administering 5 mg warfarin daily for 4 days and checking the anticoagulation status via the international normalized ratio (INR) on the fifth day could predict an early warfarin maintenance dose.

POPULATION STUDIED: This study included 61 outpatients with nonrheumatic atrial fibrillation, not receiving heparin, between the ages of 42 to 88 years (mean age = 71 years). Patients were excluded from the study if they were being treated with a drug known to interact with warfarin or had a coagulation disorder, contraindication to warfarin therapy, previous course of anticoagulation treatment, or baseline INR > 1.2, or if they refused to participate.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which patients were given 5 mg warfarin daily for 4 days (day 1 to day 4). The INR was measured on day 5 and the patient’s physician freely chose a new dose. The INR was checked at least once a week for the next 2 weeks. Patients were followed for 3 months. The warfarin dose was considered stable when the INR was between 2 and 3 on 3 consecutive occasions at least 1 week apart. The stable weekly warfarin dose was plotted against the INR obtained on the fifth day of initiation to establish a scheme for predicting an early warfarin maintenance dose. To test the validity of this scheme, 23 additional patients with nonrheumatic atrial fibrillation were given the predicted warfarin maintenance dose based on their INR on day 5 and were followed for 3 months. Although the characteristics of this additional group of patients were not stated, these subjects were enrolled according to the same criteria.

OUTCOMES MEASURED: The outcome of this study was to determine whether the INR on day 5 of warfarin treatment could predict an early warfarin maintenance dose. Major and minor bleeding episodes and thromboembolic complications were also measured.

RESULTS: Of 91 patients eligible to participate in the study, 61 were included in the analysis. Thirty patients could not be evaluated either because they failed to reach a therapeutic INR within 3 months or because they did not complete the follow-up period. The relationship between the weekly maintenance dose and the INR on day 5 followed a hyperbolic curve, demonstrating a direct relationship between the INR on day 5 and the weekly warfarin dose. During the evaluation phase that was conducted in 23 additional patients, the mean difference between the predicted and actual doses of warfarin was 1.6 mg/week (95% CI, .0007-3.195 mg) with a maximum difference of 9 mg/week. One minor bleeding episode was reported among the 61 initial patients and 23 additional patients. The dosing regimen, based on the INR after 4 days of 5 mg warfarin, is shown in the Table.

TABLE
WARFARIN DOSING REGIMEN USED IN STUDY

ABSTRACT

BACKGROUND: Initiating warfarin in patients with atrial fibrillation at a typical loading dose of 10 mg daily for 2 days may be associated with excess anticoagulation, especially in older patients. In addition, daily monitoring associated with this regimen may be inconvenient for outpatients. Initiating warfarin at 5 mg daily may produce more consistent anticoagulation and eliminate the need for daily monitoring. The investigators tested whether administering 5 mg warfarin daily for 4 days and checking the anticoagulation status via the international normalized ratio (INR) on the fifth day could predict an early warfarin maintenance dose.

POPULATION STUDIED: This study included 61 outpatients with nonrheumatic atrial fibrillation, not receiving heparin, between the ages of 42 to 88 years (mean age = 71 years). Patients were excluded from the study if they were being treated with a drug known to interact with warfarin or had a coagulation disorder, contraindication to warfarin therapy, previous course of anticoagulation treatment, or baseline INR > 1.2, or if they refused to participate.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which patients were given 5 mg warfarin daily for 4 days (day 1 to day 4). The INR was measured on day 5 and the patient’s physician freely chose a new dose. The INR was checked at least once a week for the next 2 weeks. Patients were followed for 3 months. The warfarin dose was considered stable when the INR was between 2 and 3 on 3 consecutive occasions at least 1 week apart. The stable weekly warfarin dose was plotted against the INR obtained on the fifth day of initiation to establish a scheme for predicting an early warfarin maintenance dose. To test the validity of this scheme, 23 additional patients with nonrheumatic atrial fibrillation were given the predicted warfarin maintenance dose based on their INR on day 5 and were followed for 3 months. Although the characteristics of this additional group of patients were not stated, these subjects were enrolled according to the same criteria.

OUTCOMES MEASURED: The outcome of this study was to determine whether the INR on day 5 of warfarin treatment could predict an early warfarin maintenance dose. Major and minor bleeding episodes and thromboembolic complications were also measured.

RESULTS: Of 91 patients eligible to participate in the study, 61 were included in the analysis. Thirty patients could not be evaluated either because they failed to reach a therapeutic INR within 3 months or because they did not complete the follow-up period. The relationship between the weekly maintenance dose and the INR on day 5 followed a hyperbolic curve, demonstrating a direct relationship between the INR on day 5 and the weekly warfarin dose. During the evaluation phase that was conducted in 23 additional patients, the mean difference between the predicted and actual doses of warfarin was 1.6 mg/week (95% CI, .0007-3.195 mg) with a maximum difference of 9 mg/week. One minor bleeding episode was reported among the 61 initial patients and 23 additional patients. The dosing regimen, based on the INR after 4 days of 5 mg warfarin, is shown in the Table.

TABLE
WARFARIN DOSING REGIMEN USED IN STUDY

ABSTRACT

BACKGROUND: Initiating warfarin in patients with atrial fibrillation at a typical loading dose of 10 mg daily for 2 days may be associated with excess anticoagulation, especially in older patients. In addition, daily monitoring associated with this regimen may be inconvenient for outpatients. Initiating warfarin at 5 mg daily may produce more consistent anticoagulation and eliminate the need for daily monitoring. The investigators tested whether administering 5 mg warfarin daily for 4 days and checking the anticoagulation status via the international normalized ratio (INR) on the fifth day could predict an early warfarin maintenance dose.

POPULATION STUDIED: This study included 61 outpatients with nonrheumatic atrial fibrillation, not receiving heparin, between the ages of 42 to 88 years (mean age = 71 years). Patients were excluded from the study if they were being treated with a drug known to interact with warfarin or had a coagulation disorder, contraindication to warfarin therapy, previous course of anticoagulation treatment, or baseline INR > 1.2, or if they refused to participate.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which patients were given 5 mg warfarin daily for 4 days (day 1 to day 4). The INR was measured on day 5 and the patient’s physician freely chose a new dose. The INR was checked at least once a week for the next 2 weeks. Patients were followed for 3 months. The warfarin dose was considered stable when the INR was between 2 and 3 on 3 consecutive occasions at least 1 week apart. The stable weekly warfarin dose was plotted against the INR obtained on the fifth day of initiation to establish a scheme for predicting an early warfarin maintenance dose. To test the validity of this scheme, 23 additional patients with nonrheumatic atrial fibrillation were given the predicted warfarin maintenance dose based on their INR on day 5 and were followed for 3 months. Although the characteristics of this additional group of patients were not stated, these subjects were enrolled according to the same criteria.

OUTCOMES MEASURED: The outcome of this study was to determine whether the INR on day 5 of warfarin treatment could predict an early warfarin maintenance dose. Major and minor bleeding episodes and thromboembolic complications were also measured.

RESULTS: Of 91 patients eligible to participate in the study, 61 were included in the analysis. Thirty patients could not be evaluated either because they failed to reach a therapeutic INR within 3 months or because they did not complete the follow-up period. The relationship between the weekly maintenance dose and the INR on day 5 followed a hyperbolic curve, demonstrating a direct relationship between the INR on day 5 and the weekly warfarin dose. During the evaluation phase that was conducted in 23 additional patients, the mean difference between the predicted and actual doses of warfarin was 1.6 mg/week (95% CI, .0007-3.195 mg) with a maximum difference of 9 mg/week. One minor bleeding episode was reported among the 61 initial patients and 23 additional patients. The dosing regimen, based on the INR after 4 days of 5 mg warfarin, is shown in the Table.

TABLE
WARFARIN DOSING REGIMEN USED IN STUDY

ABSTRACT

BACKGROUND: Regardless of the intervention used, relapse after initial smoking cessation occurs in 70% to 80% of patients within 6 to 12 months. The investigators studied whether continuing bupropion treatment after initial success would decrease the relapse rate.

POPULATION STUDIED: The investigators enrolled 784 men and women, aged 18 years or older, who had smoked 15 cigarettes or more per day for the previous year. Participants were motivated to stop smoking and were generally in good health. The investigators excluded persons dependent on alcohol or other non-nicotine substances in the previous year, those using psychotropic medications or with a history of bupropion use, those currently using tobacco products other than cigarettes, and those currently using another therapy for smoking cessation.

STUDY DESIGN AND VALIDITY: This was a multi-center randomized double-blind placebo-controlled trial. All participants were given self-help material and took 300 mg bupropion sustained-release daily for 7 weeks. The subjects were instructed to set a target quit date 1 week after initiating treatment. Participants who had abstained from smoking cigarettes at week 7 were randomized to receive either bupropion or placebo for a total of 1 year. Allocation to treatment group was concealed and intention-to-treat analyses were performed. Participants returned for 14 visits during the first year (the medication phase) and for 5 visits during the follow-up year. All participants received the same educational material and counseling at each visit throughout the study.

OUTCOMES MEASURED: The study had 3 primary outcomes: (1) abstinence the week preceding each visit during the first year; (2) continuous abstinence during medication treatment; and (3) time to first relapse. Smoking status was defined by self-report of abstinence over the previous 7 days, confirmed with an expired air / carbon monoxide measurement at each visit. Relapse was defined by self-report, by expired air / carbon monoxide levels, or by missing 2 or more consecutive visits. Participants who were abstinent at every visit were classified as continuously abstinent.

RESULTS: Of the 784 participants enrolled in the open-label bupropion phase of the study, 461 (58.8%) were abstinent at week 7. Of these, 429 were randomized to receive placebo or bupropion for 45 weeks. A total of 347 (80.9%) remained in the study through the first year. Most participants (317, 73.9%) completed the entire 2 years of the study. Dropout rates were similar in the treated and untreated groups. At the end of 1 year, 55.1% of the treated patients were not smoking, compared with 42.3% in the placebo group (P= .001, NNT=8). At 18 months, significantly more treated patients were still not smoking (47.7% vs 37.7%, number needed to treat = 10). At the end of 2 years, however, abstinence rates were similar for the 2 groups (41.6% vs 40%). The drug was well tolerated. Insomnia and headache were the most common adverse effects.

ABSTRACT

BACKGROUND: Regardless of the intervention used, relapse after initial smoking cessation occurs in 70% to 80% of patients within 6 to 12 months. The investigators studied whether continuing bupropion treatment after initial success would decrease the relapse rate.

POPULATION STUDIED: The investigators enrolled 784 men and women, aged 18 years or older, who had smoked 15 cigarettes or more per day for the previous year. Participants were motivated to stop smoking and were generally in good health. The investigators excluded persons dependent on alcohol or other non-nicotine substances in the previous year, those using psychotropic medications or with a history of bupropion use, those currently using tobacco products other than cigarettes, and those currently using another therapy for smoking cessation.

STUDY DESIGN AND VALIDITY: This was a multi-center randomized double-blind placebo-controlled trial. All participants were given self-help material and took 300 mg bupropion sustained-release daily for 7 weeks. The subjects were instructed to set a target quit date 1 week after initiating treatment. Participants who had abstained from smoking cigarettes at week 7 were randomized to receive either bupropion or placebo for a total of 1 year. Allocation to treatment group was concealed and intention-to-treat analyses were performed. Participants returned for 14 visits during the first year (the medication phase) and for 5 visits during the follow-up year. All participants received the same educational material and counseling at each visit throughout the study.

OUTCOMES MEASURED: The study had 3 primary outcomes: (1) abstinence the week preceding each visit during the first year; (2) continuous abstinence during medication treatment; and (3) time to first relapse. Smoking status was defined by self-report of abstinence over the previous 7 days, confirmed with an expired air / carbon monoxide measurement at each visit. Relapse was defined by self-report, by expired air / carbon monoxide levels, or by missing 2 or more consecutive visits. Participants who were abstinent at every visit were classified as continuously abstinent.

RESULTS: Of the 784 participants enrolled in the open-label bupropion phase of the study, 461 (58.8%) were abstinent at week 7. Of these, 429 were randomized to receive placebo or bupropion for 45 weeks. A total of 347 (80.9%) remained in the study through the first year. Most participants (317, 73.9%) completed the entire 2 years of the study. Dropout rates were similar in the treated and untreated groups. At the end of 1 year, 55.1% of the treated patients were not smoking, compared with 42.3% in the placebo group (P= .001, NNT=8). At 18 months, significantly more treated patients were still not smoking (47.7% vs 37.7%, number needed to treat = 10). At the end of 2 years, however, abstinence rates were similar for the 2 groups (41.6% vs 40%). The drug was well tolerated. Insomnia and headache were the most common adverse effects.

ABSTRACT

BACKGROUND: Regardless of the intervention used, relapse after initial smoking cessation occurs in 70% to 80% of patients within 6 to 12 months. The investigators studied whether continuing bupropion treatment after initial success would decrease the relapse rate.

POPULATION STUDIED: The investigators enrolled 784 men and women, aged 18 years or older, who had smoked 15 cigarettes or more per day for the previous year. Participants were motivated to stop smoking and were generally in good health. The investigators excluded persons dependent on alcohol or other non-nicotine substances in the previous year, those using psychotropic medications or with a history of bupropion use, those currently using tobacco products other than cigarettes, and those currently using another therapy for smoking cessation.

STUDY DESIGN AND VALIDITY: This was a multi-center randomized double-blind placebo-controlled trial. All participants were given self-help material and took 300 mg bupropion sustained-release daily for 7 weeks. The subjects were instructed to set a target quit date 1 week after initiating treatment. Participants who had abstained from smoking cigarettes at week 7 were randomized to receive either bupropion or placebo for a total of 1 year. Allocation to treatment group was concealed and intention-to-treat analyses were performed. Participants returned for 14 visits during the first year (the medication phase) and for 5 visits during the follow-up year. All participants received the same educational material and counseling at each visit throughout the study.

OUTCOMES MEASURED: The study had 3 primary outcomes: (1) abstinence the week preceding each visit during the first year; (2) continuous abstinence during medication treatment; and (3) time to first relapse. Smoking status was defined by self-report of abstinence over the previous 7 days, confirmed with an expired air / carbon monoxide measurement at each visit. Relapse was defined by self-report, by expired air / carbon monoxide levels, or by missing 2 or more consecutive visits. Participants who were abstinent at every visit were classified as continuously abstinent.

RESULTS: Of the 784 participants enrolled in the open-label bupropion phase of the study, 461 (58.8%) were abstinent at week 7. Of these, 429 were randomized to receive placebo or bupropion for 45 weeks. A total of 347 (80.9%) remained in the study through the first year. Most participants (317, 73.9%) completed the entire 2 years of the study. Dropout rates were similar in the treated and untreated groups. At the end of 1 year, 55.1% of the treated patients were not smoking, compared with 42.3% in the placebo group (P= .001, NNT=8). At 18 months, significantly more treated patients were still not smoking (47.7% vs 37.7%, number needed to treat = 10). At the end of 2 years, however, abstinence rates were similar for the 2 groups (41.6% vs 40%). The drug was well tolerated. Insomnia and headache were the most common adverse effects.

ABSTRACT

BACKGROUND: Acute cough and bronchitis are common primary care diagnoses often treated withβ₂-agonists (eg, albuterol). This systematic review sought to assess whether β₂-agonists constitute effective treatment for these conditions.

POPULATION STUDIED: A total of 492 patients older than 2 years was gathered from randomized controlled trials measuring the efficacy of β₂-agonists versus placebo or erythromycin for treatment of “acute cough,” “acute bronchitis,” or “acute transient cough” without clear etiology (pneumonia, pertussis, or sinusitis). The maximum mean duration of cough acceptable for inclusion was 30 days. Although no information was provided about specific diagnostic criteria, numbers of adult smokers and wheezers, or specifics of clinical presentation (fever, tachypnea), the population studied seems similar to that of a typical family practice.

STUDY DESIGN AND VALIDITY: The authors searched multiple databases, including MEDLINE and EMBASE, The Cochrane Library, reference lists of retrieved articles, review articles, textbooks, and information from manufacturers. Two investigators examined the search results, forwarding those that met inclusion criteria to the remaining 3 investigators, who graded the studies using the Jadad methodology scale, on the basis of randomization, blinding, and withdrawals. Disagreement regarding study quality was common (κ= 0.27) and was resolved by discussion. Included studies were then divided into 3 groups for analysis: 2 pediatric trials comparing β₂-agonists with placebo; 4 adult trials comparing β₂-agonists with placebo; and 1 adult trial comparing β₂-agonists with erythromycin. Summary statistics were generated using Review Manager 4.1.

OUTCOMES MEASURED: Outcomes measured included cough severity, duration, and productivity; lost work days; night cough; and adverse effects. Only one trial measured compliance. Cost and patient satisfaction were not addressed.

RESULTS: The overall quality of the included studies was fair. The pediatric studies revealed no benefit from albuterol. In the adult placebo trials, 1 demonstrated no benefit and 3 demonstrated slight improvement in cough severity. In the erythromycin study, those in the albuterol group had less cough or productive cough after 7 days, but the groups did not differ in night cough, time to improvement, or missed work days. When all the adult studies were combined, there was no difference in cough after 7 days, in productive cough, or in night cough. Studies that had enrolled more wheezing patients were more likely to show benefits than those that had not.

ABSTRACT

BACKGROUND: Acute cough and bronchitis are common primary care diagnoses often treated withβ₂-agonists (eg, albuterol). This systematic review sought to assess whether β₂-agonists constitute effective treatment for these conditions.

POPULATION STUDIED: A total of 492 patients older than 2 years was gathered from randomized controlled trials measuring the efficacy of β₂-agonists versus placebo or erythromycin for treatment of “acute cough,” “acute bronchitis,” or “acute transient cough” without clear etiology (pneumonia, pertussis, or sinusitis). The maximum mean duration of cough acceptable for inclusion was 30 days. Although no information was provided about specific diagnostic criteria, numbers of adult smokers and wheezers, or specifics of clinical presentation (fever, tachypnea), the population studied seems similar to that of a typical family practice.

STUDY DESIGN AND VALIDITY: The authors searched multiple databases, including MEDLINE and EMBASE, The Cochrane Library, reference lists of retrieved articles, review articles, textbooks, and information from manufacturers. Two investigators examined the search results, forwarding those that met inclusion criteria to the remaining 3 investigators, who graded the studies using the Jadad methodology scale, on the basis of randomization, blinding, and withdrawals. Disagreement regarding study quality was common (κ= 0.27) and was resolved by discussion. Included studies were then divided into 3 groups for analysis: 2 pediatric trials comparing β₂-agonists with placebo; 4 adult trials comparing β₂-agonists with placebo; and 1 adult trial comparing β₂-agonists with erythromycin. Summary statistics were generated using Review Manager 4.1.

OUTCOMES MEASURED: Outcomes measured included cough severity, duration, and productivity; lost work days; night cough; and adverse effects. Only one trial measured compliance. Cost and patient satisfaction were not addressed.

RESULTS: The overall quality of the included studies was fair. The pediatric studies revealed no benefit from albuterol. In the adult placebo trials, 1 demonstrated no benefit and 3 demonstrated slight improvement in cough severity. In the erythromycin study, those in the albuterol group had less cough or productive cough after 7 days, but the groups did not differ in night cough, time to improvement, or missed work days. When all the adult studies were combined, there was no difference in cough after 7 days, in productive cough, or in night cough. Studies that had enrolled more wheezing patients were more likely to show benefits than those that had not.

ABSTRACT

BACKGROUND: Acute cough and bronchitis are common primary care diagnoses often treated withβ₂-agonists (eg, albuterol). This systematic review sought to assess whether β₂-agonists constitute effective treatment for these conditions.

POPULATION STUDIED: A total of 492 patients older than 2 years was gathered from randomized controlled trials measuring the efficacy of β₂-agonists versus placebo or erythromycin for treatment of “acute cough,” “acute bronchitis,” or “acute transient cough” without clear etiology (pneumonia, pertussis, or sinusitis). The maximum mean duration of cough acceptable for inclusion was 30 days. Although no information was provided about specific diagnostic criteria, numbers of adult smokers and wheezers, or specifics of clinical presentation (fever, tachypnea), the population studied seems similar to that of a typical family practice.

STUDY DESIGN AND VALIDITY: The authors searched multiple databases, including MEDLINE and EMBASE, The Cochrane Library, reference lists of retrieved articles, review articles, textbooks, and information from manufacturers. Two investigators examined the search results, forwarding those that met inclusion criteria to the remaining 3 investigators, who graded the studies using the Jadad methodology scale, on the basis of randomization, blinding, and withdrawals. Disagreement regarding study quality was common (κ= 0.27) and was resolved by discussion. Included studies were then divided into 3 groups for analysis: 2 pediatric trials comparing β₂-agonists with placebo; 4 adult trials comparing β₂-agonists with placebo; and 1 adult trial comparing β₂-agonists with erythromycin. Summary statistics were generated using Review Manager 4.1.

OUTCOMES MEASURED: Outcomes measured included cough severity, duration, and productivity; lost work days; night cough; and adverse effects. Only one trial measured compliance. Cost and patient satisfaction were not addressed.

RESULTS: The overall quality of the included studies was fair. The pediatric studies revealed no benefit from albuterol. In the adult placebo trials, 1 demonstrated no benefit and 3 demonstrated slight improvement in cough severity. In the erythromycin study, those in the albuterol group had less cough or productive cough after 7 days, but the groups did not differ in night cough, time to improvement, or missed work days. When all the adult studies were combined, there was no difference in cough after 7 days, in productive cough, or in night cough. Studies that had enrolled more wheezing patients were more likely to show benefits than those that had not.

ABSTRACT

BACKGROUND: Simple viral respiratory infections (the common cold) often predispose patients with COPD to lower respiratory infections and subsequent exacerbations. Low-dose, long-term erythromycin therapy has been reported to treat diffuse panbronchiolitis and bronchiectasis by anti-inflammatory mechanisms rather than through its inherent antibacterial mechanisms. Macrolide antibiotics have also been reported to have antiviral protective mechanisms. This study investigated the frequency of common colds and COPD exacerbations in patients treated with low-dose, long-term erythromycin.

POPULATION STUDIED: This Japanese study included 109 patients with COPD as defined by the American Thoracic Society. Subjects could be treated with sustained-released theophylline and inhaled anticholinergic agents, but not corticosteroids. The investigators excluded patients with diffuse panbronchiolitis or bronchiectasis.

STUDY DESIGN AND VALIDITY: This was a randomized, nonblinded study conducted over 12 months. One group of 55 patients received erythromycin (200-400 mg daily); the control group of 54 patients received 10 mg riboflavin daily. The investigators were unaware which treatments would be given before enrolling patients into the study (ie, allocation was concealed). The groups were similar in age, sex, and baseline lung function. Patients self-reported daily symptoms, including sneezing, nasal discharge, malaise, headache, chills, fever, sore throat, hoarseness, and cough, and rated each for severity on a scale of 0 to 3. An episode of common cold was defined as a quantitative symptom score of >5. COPD exacerbations were defined as a worsening in symptoms requiring changes to the regular pharmacologic regimen, including the need for antimicrobial or systemic steroid therapy. Exacerbations were graded based on need for hospitalization: mild and moderate, if treatment did not require hospitalization; severe, if hospitalization was required. Physicians evaluated their patients every 2 weeks. Patients who had cold symptoms were encouraged to visit the hospital for investigator-initiated checks.

OUTCOMES MEASURED: The investigators measured the number of common colds and the frequency and severity of COPD exacerbations.

RESULTS: The number of common colds was significantly lower in the erythromycin group than in the control group (1.24 vs 4.54 episodes per person; P = .002). Over a 12-month period, 76% of the control group subjects experienced more than one cold, compared with 13% in the erythromycin group (relative risk = 9.26; 95% CI, 3.92-31.74, number needed to treat [NNT] = 1.6). The percentage of patients having one or more COPD exacerbations was significantly higher in the control group (54% vs 11%; RR = 4.71; 95% CI, 1.53-14.5; NNT = 2.2). The control group experienced 11 severe exacerbations; the erythromycin group had none. The total number and severity of COPD exacerbations were also significantly lower in the erythromycin group than in the control group. No deaths were reported during the study period. One patient in the erythromycin group was excluded because of adverse effects of treatment (diarrhea and anorexia).

ABSTRACT

BACKGROUND: Simple viral respiratory infections (the common cold) often predispose patients with COPD to lower respiratory infections and subsequent exacerbations. Low-dose, long-term erythromycin therapy has been reported to treat diffuse panbronchiolitis and bronchiectasis by anti-inflammatory mechanisms rather than through its inherent antibacterial mechanisms. Macrolide antibiotics have also been reported to have antiviral protective mechanisms. This study investigated the frequency of common colds and COPD exacerbations in patients treated with low-dose, long-term erythromycin.

POPULATION STUDIED: This Japanese study included 109 patients with COPD as defined by the American Thoracic Society. Subjects could be treated with sustained-released theophylline and inhaled anticholinergic agents, but not corticosteroids. The investigators excluded patients with diffuse panbronchiolitis or bronchiectasis.

STUDY DESIGN AND VALIDITY: This was a randomized, nonblinded study conducted over 12 months. One group of 55 patients received erythromycin (200-400 mg daily); the control group of 54 patients received 10 mg riboflavin daily. The investigators were unaware which treatments would be given before enrolling patients into the study (ie, allocation was concealed). The groups were similar in age, sex, and baseline lung function. Patients self-reported daily symptoms, including sneezing, nasal discharge, malaise, headache, chills, fever, sore throat, hoarseness, and cough, and rated each for severity on a scale of 0 to 3. An episode of common cold was defined as a quantitative symptom score of >5. COPD exacerbations were defined as a worsening in symptoms requiring changes to the regular pharmacologic regimen, including the need for antimicrobial or systemic steroid therapy. Exacerbations were graded based on need for hospitalization: mild and moderate, if treatment did not require hospitalization; severe, if hospitalization was required. Physicians evaluated their patients every 2 weeks. Patients who had cold symptoms were encouraged to visit the hospital for investigator-initiated checks.

OUTCOMES MEASURED: The investigators measured the number of common colds and the frequency and severity of COPD exacerbations.

RESULTS: The number of common colds was significantly lower in the erythromycin group than in the control group (1.24 vs 4.54 episodes per person; P = .002). Over a 12-month period, 76% of the control group subjects experienced more than one cold, compared with 13% in the erythromycin group (relative risk = 9.26; 95% CI, 3.92-31.74, number needed to treat [NNT] = 1.6). The percentage of patients having one or more COPD exacerbations was significantly higher in the control group (54% vs 11%; RR = 4.71; 95% CI, 1.53-14.5; NNT = 2.2). The control group experienced 11 severe exacerbations; the erythromycin group had none. The total number and severity of COPD exacerbations were also significantly lower in the erythromycin group than in the control group. No deaths were reported during the study period. One patient in the erythromycin group was excluded because of adverse effects of treatment (diarrhea and anorexia).

ABSTRACT

BACKGROUND: Simple viral respiratory infections (the common cold) often predispose patients with COPD to lower respiratory infections and subsequent exacerbations. Low-dose, long-term erythromycin therapy has been reported to treat diffuse panbronchiolitis and bronchiectasis by anti-inflammatory mechanisms rather than through its inherent antibacterial mechanisms. Macrolide antibiotics have also been reported to have antiviral protective mechanisms. This study investigated the frequency of common colds and COPD exacerbations in patients treated with low-dose, long-term erythromycin.

POPULATION STUDIED: This Japanese study included 109 patients with COPD as defined by the American Thoracic Society. Subjects could be treated with sustained-released theophylline and inhaled anticholinergic agents, but not corticosteroids. The investigators excluded patients with diffuse panbronchiolitis or bronchiectasis.

STUDY DESIGN AND VALIDITY: This was a randomized, nonblinded study conducted over 12 months. One group of 55 patients received erythromycin (200-400 mg daily); the control group of 54 patients received 10 mg riboflavin daily. The investigators were unaware which treatments would be given before enrolling patients into the study (ie, allocation was concealed). The groups were similar in age, sex, and baseline lung function. Patients self-reported daily symptoms, including sneezing, nasal discharge, malaise, headache, chills, fever, sore throat, hoarseness, and cough, and rated each for severity on a scale of 0 to 3. An episode of common cold was defined as a quantitative symptom score of >5. COPD exacerbations were defined as a worsening in symptoms requiring changes to the regular pharmacologic regimen, including the need for antimicrobial or systemic steroid therapy. Exacerbations were graded based on need for hospitalization: mild and moderate, if treatment did not require hospitalization; severe, if hospitalization was required. Physicians evaluated their patients every 2 weeks. Patients who had cold symptoms were encouraged to visit the hospital for investigator-initiated checks.

OUTCOMES MEASURED: The investigators measured the number of common colds and the frequency and severity of COPD exacerbations.

RESULTS: The number of common colds was significantly lower in the erythromycin group than in the control group (1.24 vs 4.54 episodes per person; P = .002). Over a 12-month period, 76% of the control group subjects experienced more than one cold, compared with 13% in the erythromycin group (relative risk = 9.26; 95% CI, 3.92-31.74, number needed to treat [NNT] = 1.6). The percentage of patients having one or more COPD exacerbations was significantly higher in the control group (54% vs 11%; RR = 4.71; 95% CI, 1.53-14.5; NNT = 2.2). The control group experienced 11 severe exacerbations; the erythromycin group had none. The total number and severity of COPD exacerbations were also significantly lower in the erythromycin group than in the control group. No deaths were reported during the study period. One patient in the erythromycin group was excluded because of adverse effects of treatment (diarrhea and anorexia).

ABSTRACT

BACKGROUND: There is great variation in treatment strategies for community-acquired pneumonia. The authors of this study compared the safety, efficacy, and cost of oral therapy (in nonsevere pneumonia) and early switch to oral therapy (in severe pneumonia) with conventional parenteral treatment of community-acquired pneumonia in hospitalized patients.

POPULATION STUDIED: The investigators enrolled 235 adults, 188 of whom were included in the final analysis. The patients had a diagnosis of pneumonia on the basis of clinical, laboratory, and radiologic criteria. Hospitalization was considered according to published standards: age >60 years, comorbid conditions, or severity criteria (PaO₂ <60mmHg, respiratory rate ≥30/min, heart rate at least 125/min, systolic blood pressure <90mmHg, temperature of ≥40°C or <35°C, altered mental status, multilobar involvement, or patients treated appropriately for 72 hours who showed deterioration or no improvement. Patients were excluded if they had been discharged from an acute-care facility in the previous 8 days or had nosocomial pneumonia, AIDS, aspiration pneumonia, extrapulmonary septic metastases, malabsorption, or problems swallowing. Patients were also excluded if they were pregnant or lactating or had criteria for admission to the intensive care unit. Patients were split into 2 study groups: those with nonsevere pneumonia who required hospitalization but did not meet any of these severity criteria, and those who had at least one severity criterion.

STUDY DESIGN AND VALIDITY: This is a nonblinded, randomized controlled trial. The patients in both the nonsevere and the severe pneumonia groups were assigned to either a new therapeutic strategy or conventional treatment. Allocation was not concealed.

OUTCOMES MEASURED: The main outcomes were treatment failure, including death, time to resolution of morbidity, and cost. Other outcomes were length of hospital stay, length of IV and total antibiotic therapy, time until resumption of normal activities, radio-logic worsening at 48 hours, and adverse events.

RESULTS: In patients with nonsevere pneumonia, no significant differences were found in mortality or time to resolution of morbidity between those assigned to oral therapy and those assigned to IV therapy. Patients receiving parental therapy had significantly more treatment failures in those receiving oral therapy (number needed to treat [NNT] = 5). In patients with severe pneumonia, no significant differences were found in mortality, time to resolution of morbidity, or treatment failures. Fewer adverse events occurred in the oral and early-switch groups, largely because of infusion-related phlebitis (NNT = 4). Significant cost savings occurred among patients with severe pneumonia in the early-switch group, primarily because of their shorter hospitalization.

ABSTRACT

BACKGROUND: There is great variation in treatment strategies for community-acquired pneumonia. The authors of this study compared the safety, efficacy, and cost of oral therapy (in nonsevere pneumonia) and early switch to oral therapy (in severe pneumonia) with conventional parenteral treatment of community-acquired pneumonia in hospitalized patients.

POPULATION STUDIED: The investigators enrolled 235 adults, 188 of whom were included in the final analysis. The patients had a diagnosis of pneumonia on the basis of clinical, laboratory, and radiologic criteria. Hospitalization was considered according to published standards: age >60 years, comorbid conditions, or severity criteria (PaO₂ <60mmHg, respiratory rate ≥30/min, heart rate at least 125/min, systolic blood pressure <90mmHg, temperature of ≥40°C or <35°C, altered mental status, multilobar involvement, or patients treated appropriately for 72 hours who showed deterioration or no improvement. Patients were excluded if they had been discharged from an acute-care facility in the previous 8 days or had nosocomial pneumonia, AIDS, aspiration pneumonia, extrapulmonary septic metastases, malabsorption, or problems swallowing. Patients were also excluded if they were pregnant or lactating or had criteria for admission to the intensive care unit. Patients were split into 2 study groups: those with nonsevere pneumonia who required hospitalization but did not meet any of these severity criteria, and those who had at least one severity criterion.

STUDY DESIGN AND VALIDITY: This is a nonblinded, randomized controlled trial. The patients in both the nonsevere and the severe pneumonia groups were assigned to either a new therapeutic strategy or conventional treatment. Allocation was not concealed.

OUTCOMES MEASURED: The main outcomes were treatment failure, including death, time to resolution of morbidity, and cost. Other outcomes were length of hospital stay, length of IV and total antibiotic therapy, time until resumption of normal activities, radio-logic worsening at 48 hours, and adverse events.

RESULTS: In patients with nonsevere pneumonia, no significant differences were found in mortality or time to resolution of morbidity between those assigned to oral therapy and those assigned to IV therapy. Patients receiving parental therapy had significantly more treatment failures in those receiving oral therapy (number needed to treat [NNT] = 5). In patients with severe pneumonia, no significant differences were found in mortality, time to resolution of morbidity, or treatment failures. Fewer adverse events occurred in the oral and early-switch groups, largely because of infusion-related phlebitis (NNT = 4). Significant cost savings occurred among patients with severe pneumonia in the early-switch group, primarily because of their shorter hospitalization.

ABSTRACT

BACKGROUND: There is great variation in treatment strategies for community-acquired pneumonia. The authors of this study compared the safety, efficacy, and cost of oral therapy (in nonsevere pneumonia) and early switch to oral therapy (in severe pneumonia) with conventional parenteral treatment of community-acquired pneumonia in hospitalized patients.

POPULATION STUDIED: The investigators enrolled 235 adults, 188 of whom were included in the final analysis. The patients had a diagnosis of pneumonia on the basis of clinical, laboratory, and radiologic criteria. Hospitalization was considered according to published standards: age >60 years, comorbid conditions, or severity criteria (PaO₂ <60mmHg, respiratory rate ≥30/min, heart rate at least 125/min, systolic blood pressure <90mmHg, temperature of ≥40°C or <35°C, altered mental status, multilobar involvement, or patients treated appropriately for 72 hours who showed deterioration or no improvement. Patients were excluded if they had been discharged from an acute-care facility in the previous 8 days or had nosocomial pneumonia, AIDS, aspiration pneumonia, extrapulmonary septic metastases, malabsorption, or problems swallowing. Patients were also excluded if they were pregnant or lactating or had criteria for admission to the intensive care unit. Patients were split into 2 study groups: those with nonsevere pneumonia who required hospitalization but did not meet any of these severity criteria, and those who had at least one severity criterion.

STUDY DESIGN AND VALIDITY: This is a nonblinded, randomized controlled trial. The patients in both the nonsevere and the severe pneumonia groups were assigned to either a new therapeutic strategy or conventional treatment. Allocation was not concealed.

OUTCOMES MEASURED: The main outcomes were treatment failure, including death, time to resolution of morbidity, and cost. Other outcomes were length of hospital stay, length of IV and total antibiotic therapy, time until resumption of normal activities, radio-logic worsening at 48 hours, and adverse events.

RESULTS: In patients with nonsevere pneumonia, no significant differences were found in mortality or time to resolution of morbidity between those assigned to oral therapy and those assigned to IV therapy. Patients receiving parental therapy had significantly more treatment failures in those receiving oral therapy (number needed to treat [NNT] = 5). In patients with severe pneumonia, no significant differences were found in mortality, time to resolution of morbidity, or treatment failures. Fewer adverse events occurred in the oral and early-switch groups, largely because of infusion-related phlebitis (NNT = 4). Significant cost savings occurred among patients with severe pneumonia in the early-switch group, primarily because of their shorter hospitalization.

ABSTRACT

BACKGROUND: Progestational therapy has been claimed effective in patients with PMS for many years. In the United States, progesterone or progestogen products account for 60% to 70% of prescriptions for PMS symptoms.

POPULATION STUDIED: The authors searched for clinical trials of progesterone or progestogens in the management of PMS. A systematic search of multiple databases in all languages yielded the reports of clinical trials included in this review. A search of references cited and contact with pharmaceutical companies completed the list of trials for evaluation. The report does not indicate whether searches were performed by more than one person. Trials were included if patients had a pretreatment diagnosis of PMS. Ten trials of progesterone therapy, evaluating 531 patients, remained for analysis. For progestogen therapy, analysis included 4 trials comprising a total of 378 patients. Although the authors do not describe the patients from the included trials in detail, they probably represent patients seen in family practice settings.

STUDY DESIGN AND VALIDITY: The authors of this meta-analysis evaluated all trials for quality using 2 separate rating scales. The quality of available studies was low. The authors independently extracted data in duplicate from the trials selected for analysis.

OUTCOMES MEASURED: The authors defined their primary outcome as the reduction in overall symptoms of PMS. The authors summarized outcomes by intention to treat, where possible. They calculated a standardized mean difference in effect of treatment and converted this statistic to an odds ratio (OR).

RESULTS: Trials of progesterone suppositories or pessaries showed a marginal effect in favor of placebo (OR = 0.93; 95% CI, 0.91-0.95). Oral micronized progesterone had marginal benefit (OR = 1.30; 95% CI, 1.25-1.36). When all trials of progesterone were combined, there was a small, but clinically insignificant, effect (OR = 1.05; 95% CI, 1.03-1.08). Trials of progestogen therapy showed a clinically insignificant effect in favor of the drug (OR = 1.07; 95% CI, 1.03-1.11). Patients given active treatment had a nonsignificant increase in dropout rate because of side effects (OR = 1.65; 95% CI, 0.86-3.21).

ABSTRACT

BACKGROUND: Progestational therapy has been claimed effective in patients with PMS for many years. In the United States, progesterone or progestogen products account for 60% to 70% of prescriptions for PMS symptoms.

POPULATION STUDIED: The authors searched for clinical trials of progesterone or progestogens in the management of PMS. A systematic search of multiple databases in all languages yielded the reports of clinical trials included in this review. A search of references cited and contact with pharmaceutical companies completed the list of trials for evaluation. The report does not indicate whether searches were performed by more than one person. Trials were included if patients had a pretreatment diagnosis of PMS. Ten trials of progesterone therapy, evaluating 531 patients, remained for analysis. For progestogen therapy, analysis included 4 trials comprising a total of 378 patients. Although the authors do not describe the patients from the included trials in detail, they probably represent patients seen in family practice settings.

STUDY DESIGN AND VALIDITY: The authors of this meta-analysis evaluated all trials for quality using 2 separate rating scales. The quality of available studies was low. The authors independently extracted data in duplicate from the trials selected for analysis.

OUTCOMES MEASURED: The authors defined their primary outcome as the reduction in overall symptoms of PMS. The authors summarized outcomes by intention to treat, where possible. They calculated a standardized mean difference in effect of treatment and converted this statistic to an odds ratio (OR).

RESULTS: Trials of progesterone suppositories or pessaries showed a marginal effect in favor of placebo (OR = 0.93; 95% CI, 0.91-0.95). Oral micronized progesterone had marginal benefit (OR = 1.30; 95% CI, 1.25-1.36). When all trials of progesterone were combined, there was a small, but clinically insignificant, effect (OR = 1.05; 95% CI, 1.03-1.08). Trials of progestogen therapy showed a clinically insignificant effect in favor of the drug (OR = 1.07; 95% CI, 1.03-1.11). Patients given active treatment had a nonsignificant increase in dropout rate because of side effects (OR = 1.65; 95% CI, 0.86-3.21).

ABSTRACT

BACKGROUND: Progestational therapy has been claimed effective in patients with PMS for many years. In the United States, progesterone or progestogen products account for 60% to 70% of prescriptions for PMS symptoms.

POPULATION STUDIED: The authors searched for clinical trials of progesterone or progestogens in the management of PMS. A systematic search of multiple databases in all languages yielded the reports of clinical trials included in this review. A search of references cited and contact with pharmaceutical companies completed the list of trials for evaluation. The report does not indicate whether searches were performed by more than one person. Trials were included if patients had a pretreatment diagnosis of PMS. Ten trials of progesterone therapy, evaluating 531 patients, remained for analysis. For progestogen therapy, analysis included 4 trials comprising a total of 378 patients. Although the authors do not describe the patients from the included trials in detail, they probably represent patients seen in family practice settings.

STUDY DESIGN AND VALIDITY: The authors of this meta-analysis evaluated all trials for quality using 2 separate rating scales. The quality of available studies was low. The authors independently extracted data in duplicate from the trials selected for analysis.

OUTCOMES MEASURED: The authors defined their primary outcome as the reduction in overall symptoms of PMS. The authors summarized outcomes by intention to treat, where possible. They calculated a standardized mean difference in effect of treatment and converted this statistic to an odds ratio (OR).

RESULTS: Trials of progesterone suppositories or pessaries showed a marginal effect in favor of placebo (OR = 0.93; 95% CI, 0.91-0.95). Oral micronized progesterone had marginal benefit (OR = 1.30; 95% CI, 1.25-1.36). When all trials of progesterone were combined, there was a small, but clinically insignificant, effect (OR = 1.05; 95% CI, 1.03-1.08). Trials of progestogen therapy showed a clinically insignificant effect in favor of the drug (OR = 1.07; 95% CI, 1.03-1.11). Patients given active treatment had a nonsignificant increase in dropout rate because of side effects (OR = 1.65; 95% CI, 0.86-3.21).