Q&A

BACKGROUND: Though cholesterol-lowering therapy can reduce cardiovascular morbidity and mortality, earlier studies raised concerns that reducing cholesterol concentrations might increase the risk of cancer and deaths from suicides, accidents, and violence (ie, nonillness mortality).

POPULATION STUDIED: This meta-analysis included clinical trials of cholesterol-lowering treatments in which participants were randomly assigned to a cholesterol-lowering intervention group or a control group. The investigators only included trials designed to measure effects of treatment on clinical events and mortality. Most participants were men aged between 40 and 70 years.

STUDY DESIGN AND VALIDITY: The studies were identified using an ancestry approach (locating previous studies cited in reference lists of already identified studies cited in reference articles) and a MEDLINE computer literature search from 1966 to March 2000. A total of 21 trials met inclusion criteria, though only 15 contained data on nonillness mortality. Some investigators provided previously unpublished data for 4 trials, yielding data from 19 of the 21 trials. The included studies investigated cholesterol-lowering either by drug therapy, diet modification, or both. The most common reasons for exclusion were the use of multifactorial risk interventions and studies not designed to monitor clinical events and cause-specific mortality.

OUTCOMES MEASURED: The outcomes were nonillness mortality, including suicides, accidents, and violence.

RESULTS: The studies that met inclusion criteria generated approximately 338,000 patient-years of randomized clinical trial data. Overall, treatments with the goal of lower total cholesterol did not affect the rate of nonillness mortality (odd ratio [OR]=1.18; 95% confidence interval [CI], 0.91-1.52). There was no effect in studies of primary prevention, secondary prevention, or studies of the “statin” drugs. Trials of diet and non-statin drugs (13 trials including 39,260 patients) also did not show a difference, although there was a trend toward increased nonillness mortality (OR=1.32; 95% CI, 0.98-1.77; P=.06). The absolute risk increase in these trials was 4.7 per 1000, which translates to a number needed to harm of 213.The rate of nonillness mortality was not related to the degree of cholesterol reduction.

BACKGROUND: Though cholesterol-lowering therapy can reduce cardiovascular morbidity and mortality, earlier studies raised concerns that reducing cholesterol concentrations might increase the risk of cancer and deaths from suicides, accidents, and violence (ie, nonillness mortality).

POPULATION STUDIED: This meta-analysis included clinical trials of cholesterol-lowering treatments in which participants were randomly assigned to a cholesterol-lowering intervention group or a control group. The investigators only included trials designed to measure effects of treatment on clinical events and mortality. Most participants were men aged between 40 and 70 years.

STUDY DESIGN AND VALIDITY: The studies were identified using an ancestry approach (locating previous studies cited in reference lists of already identified studies cited in reference articles) and a MEDLINE computer literature search from 1966 to March 2000. A total of 21 trials met inclusion criteria, though only 15 contained data on nonillness mortality. Some investigators provided previously unpublished data for 4 trials, yielding data from 19 of the 21 trials. The included studies investigated cholesterol-lowering either by drug therapy, diet modification, or both. The most common reasons for exclusion were the use of multifactorial risk interventions and studies not designed to monitor clinical events and cause-specific mortality.

OUTCOMES MEASURED: The outcomes were nonillness mortality, including suicides, accidents, and violence.

RESULTS: The studies that met inclusion criteria generated approximately 338,000 patient-years of randomized clinical trial data. Overall, treatments with the goal of lower total cholesterol did not affect the rate of nonillness mortality (odd ratio [OR]=1.18; 95% confidence interval [CI], 0.91-1.52). There was no effect in studies of primary prevention, secondary prevention, or studies of the “statin” drugs. Trials of diet and non-statin drugs (13 trials including 39,260 patients) also did not show a difference, although there was a trend toward increased nonillness mortality (OR=1.32; 95% CI, 0.98-1.77; P=.06). The absolute risk increase in these trials was 4.7 per 1000, which translates to a number needed to harm of 213.The rate of nonillness mortality was not related to the degree of cholesterol reduction.

BACKGROUND: Though cholesterol-lowering therapy can reduce cardiovascular morbidity and mortality, earlier studies raised concerns that reducing cholesterol concentrations might increase the risk of cancer and deaths from suicides, accidents, and violence (ie, nonillness mortality).

POPULATION STUDIED: This meta-analysis included clinical trials of cholesterol-lowering treatments in which participants were randomly assigned to a cholesterol-lowering intervention group or a control group. The investigators only included trials designed to measure effects of treatment on clinical events and mortality. Most participants were men aged between 40 and 70 years.

STUDY DESIGN AND VALIDITY: The studies were identified using an ancestry approach (locating previous studies cited in reference lists of already identified studies cited in reference articles) and a MEDLINE computer literature search from 1966 to March 2000. A total of 21 trials met inclusion criteria, though only 15 contained data on nonillness mortality. Some investigators provided previously unpublished data for 4 trials, yielding data from 19 of the 21 trials. The included studies investigated cholesterol-lowering either by drug therapy, diet modification, or both. The most common reasons for exclusion were the use of multifactorial risk interventions and studies not designed to monitor clinical events and cause-specific mortality.

OUTCOMES MEASURED: The outcomes were nonillness mortality, including suicides, accidents, and violence.

RESULTS: The studies that met inclusion criteria generated approximately 338,000 patient-years of randomized clinical trial data. Overall, treatments with the goal of lower total cholesterol did not affect the rate of nonillness mortality (odd ratio [OR]=1.18; 95% confidence interval [CI], 0.91-1.52). There was no effect in studies of primary prevention, secondary prevention, or studies of the “statin” drugs. Trials of diet and non-statin drugs (13 trials including 39,260 patients) also did not show a difference, although there was a trend toward increased nonillness mortality (OR=1.32; 95% CI, 0.98-1.77; P=.06). The absolute risk increase in these trials was 4.7 per 1000, which translates to a number needed to harm of 213.The rate of nonillness mortality was not related to the degree of cholesterol reduction.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BACKGROUND: Calcium channel blockers (CCBs) are more effective than placebo in lowering blood pressure and in preventing subsequent cardiovascular outcomes. However, observational studies of short-acting CCBs and controlled trials of long-acting CCBs have shown that although blood pressure is controlled, cardiovascular event rates increase. The authors performed a meta-analysis of randomized controlled trials comparing CCBs with first-line antihypertensives regarding their effects on cardiovascular events. population studied The analysis included 9 studies involving 27,743 patients. The mean age range was 53.9 to 76.1 years. Both men and women were represented in the analysis. Follow-up was 2 to 7 years with an estimated total follow-up of 120,000 person-years.

STUDY DESIGN AND VALIDITY: This is a meta-analysis of the existing literature. Studies were identified for inclusion through a systematic search of MEDLINE. To be included the randomized trials had to have more than 100 participants, follow-up longer than 2 years, compare CCBs with other first-line agents, and evaluate the effect on cardiovascular outcomes. The studies compared CCBs with diuretics, b-blockers, angiotensin-converting enzyme inhibitors, and clonidine. Two investigators independently abstracted data. Outcome data were analyzed by intention to treat except in one study that consisted of 429 patients. Tests for heterogeneity were performed. The meta-analysis is well done although limited by the quality of the included studies. Each of the 9 studies in the analysis has a limitation. Five of the studies were open design, and in 4 studies the authors had to contact investigators to obtain information on the primary outcomes. Two studies dealt primarily with patients with diabetes. In one study randomization favored the CCB arm, while in another the non-CCB arm had a more favorable baseline. The dropout rate for the studies ranged from 7% to 60%. A variety of sensitivity analyses were done to determine if one study, one drug type, or one type of patient profile contributed to the results. This did not appear to be the situation, although there was insufficient power in some of the sensitivity analyses to answer this question confidently.

OUTCOMES MEASURED: The outcomes measured were changes in systolic and diastolic blood pressure, acute myocardial infarctions, congestive heart failure, stroke, and all-cause mortality. The authors also evaluated the effect of treatment on the combined outcome of major cardiovascular events including acute myocardial infarction, congestive heart failure, stroke, and cardiovascular mortality.

RESULTS: CCBs lowered both systolic and diastolic blood pressure comparably with first-line agents. CCBs had a higher risk of acute myocardial infarction (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.11-1.43), congestive heart failure (OR=1.25; 95% CI, 1.07-1.46), and major cardiovascular events (OR=1.10; 95% CI, 1.02-1.18). CCBs were comparable with other agents for reducing the risk of stroke (OR=0.90; 95% CI, 0.80-1.02) and all-cause mortality (OR=1.03; 95% CI, 0.94-1.13).

BACKGROUND: Calcium channel blockers (CCBs) are more effective than placebo in lowering blood pressure and in preventing subsequent cardiovascular outcomes. However, observational studies of short-acting CCBs and controlled trials of long-acting CCBs have shown that although blood pressure is controlled, cardiovascular event rates increase. The authors performed a meta-analysis of randomized controlled trials comparing CCBs with first-line antihypertensives regarding their effects on cardiovascular events. population studied The analysis included 9 studies involving 27,743 patients. The mean age range was 53.9 to 76.1 years. Both men and women were represented in the analysis. Follow-up was 2 to 7 years with an estimated total follow-up of 120,000 person-years.

STUDY DESIGN AND VALIDITY: This is a meta-analysis of the existing literature. Studies were identified for inclusion through a systematic search of MEDLINE. To be included the randomized trials had to have more than 100 participants, follow-up longer than 2 years, compare CCBs with other first-line agents, and evaluate the effect on cardiovascular outcomes. The studies compared CCBs with diuretics, b-blockers, angiotensin-converting enzyme inhibitors, and clonidine. Two investigators independently abstracted data. Outcome data were analyzed by intention to treat except in one study that consisted of 429 patients. Tests for heterogeneity were performed. The meta-analysis is well done although limited by the quality of the included studies. Each of the 9 studies in the analysis has a limitation. Five of the studies were open design, and in 4 studies the authors had to contact investigators to obtain information on the primary outcomes. Two studies dealt primarily with patients with diabetes. In one study randomization favored the CCB arm, while in another the non-CCB arm had a more favorable baseline. The dropout rate for the studies ranged from 7% to 60%. A variety of sensitivity analyses were done to determine if one study, one drug type, or one type of patient profile contributed to the results. This did not appear to be the situation, although there was insufficient power in some of the sensitivity analyses to answer this question confidently.

OUTCOMES MEASURED: The outcomes measured were changes in systolic and diastolic blood pressure, acute myocardial infarctions, congestive heart failure, stroke, and all-cause mortality. The authors also evaluated the effect of treatment on the combined outcome of major cardiovascular events including acute myocardial infarction, congestive heart failure, stroke, and cardiovascular mortality.

RESULTS: CCBs lowered both systolic and diastolic blood pressure comparably with first-line agents. CCBs had a higher risk of acute myocardial infarction (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.11-1.43), congestive heart failure (OR=1.25; 95% CI, 1.07-1.46), and major cardiovascular events (OR=1.10; 95% CI, 1.02-1.18). CCBs were comparable with other agents for reducing the risk of stroke (OR=0.90; 95% CI, 0.80-1.02) and all-cause mortality (OR=1.03; 95% CI, 0.94-1.13).

BACKGROUND: Calcium channel blockers (CCBs) are more effective than placebo in lowering blood pressure and in preventing subsequent cardiovascular outcomes. However, observational studies of short-acting CCBs and controlled trials of long-acting CCBs have shown that although blood pressure is controlled, cardiovascular event rates increase. The authors performed a meta-analysis of randomized controlled trials comparing CCBs with first-line antihypertensives regarding their effects on cardiovascular events. population studied The analysis included 9 studies involving 27,743 patients. The mean age range was 53.9 to 76.1 years. Both men and women were represented in the analysis. Follow-up was 2 to 7 years with an estimated total follow-up of 120,000 person-years.

STUDY DESIGN AND VALIDITY: This is a meta-analysis of the existing literature. Studies were identified for inclusion through a systematic search of MEDLINE. To be included the randomized trials had to have more than 100 participants, follow-up longer than 2 years, compare CCBs with other first-line agents, and evaluate the effect on cardiovascular outcomes. The studies compared CCBs with diuretics, b-blockers, angiotensin-converting enzyme inhibitors, and clonidine. Two investigators independently abstracted data. Outcome data were analyzed by intention to treat except in one study that consisted of 429 patients. Tests for heterogeneity were performed. The meta-analysis is well done although limited by the quality of the included studies. Each of the 9 studies in the analysis has a limitation. Five of the studies were open design, and in 4 studies the authors had to contact investigators to obtain information on the primary outcomes. Two studies dealt primarily with patients with diabetes. In one study randomization favored the CCB arm, while in another the non-CCB arm had a more favorable baseline. The dropout rate for the studies ranged from 7% to 60%. A variety of sensitivity analyses were done to determine if one study, one drug type, or one type of patient profile contributed to the results. This did not appear to be the situation, although there was insufficient power in some of the sensitivity analyses to answer this question confidently.

OUTCOMES MEASURED: The outcomes measured were changes in systolic and diastolic blood pressure, acute myocardial infarctions, congestive heart failure, stroke, and all-cause mortality. The authors also evaluated the effect of treatment on the combined outcome of major cardiovascular events including acute myocardial infarction, congestive heart failure, stroke, and cardiovascular mortality.

RESULTS: CCBs lowered both systolic and diastolic blood pressure comparably with first-line agents. CCBs had a higher risk of acute myocardial infarction (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.11-1.43), congestive heart failure (OR=1.25; 95% CI, 1.07-1.46), and major cardiovascular events (OR=1.10; 95% CI, 1.02-1.18). CCBs were comparable with other agents for reducing the risk of stroke (OR=0.90; 95% CI, 0.80-1.02) and all-cause mortality (OR=1.03; 95% CI, 0.94-1.13).

BACKGROUND: Parents and clinicians have traditionally attributed to teething many symptoms, such as fever, pain, irritability, diarrhea, drooling, and sleep disturbance. However, little evidence exists to support this claim. The authors investigated the relationship between tooth eruption, fever, and teething symptoms.

POPULATION STUDIED: All children aged 6 months to 2 years from 3 Australian daycare centers were eligible for the study if they attended at least 3 days a week. Twenty-one children (78% of eligible children) participated (mean age=14.4 months), and all completed the study.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study. Data on symptoms for each child were collected using questionnaires completed by parents each morning and by daycare center staff each afternoon over a 7-month period. A dental therapist examined each of the children daily over the same time period for signs of tooth eruption and measured each child’s temperature using an infrared tympanic thermometer. Tooth eruptions were defined as the first day a tooth edge emerged from the oral mucosa and remained consistently visible. Toothdays were defined as the 5 days leading up to a tooth eruption. Non-toothdays were defined as days more than 28 days clear of an eruption. Data were compared by logistic regression analysis. The study was limited in several ways. The small sample size may have affected the power of the study to detect small but clinically significant differences. There was an attempt at blinding the participants and their parents to the purpose of the study, but this blinding was incomplete and was lost over time. Parents and daycare staff might have been inclined to over-report symptoms if a child was having a tooth eruption. There was no mention made in the study of parental administration of antipyretic or analgesic medication that may have been used to treat symptoms. Use of such medications might have affected temperature readings or the results of daycare staff questionnaires. Also, tympanic temperature readings have been found inaccurate for detecting fever compared with core temperature readings. Finally, a substantial portion of data was missing from the report (6% of dental therapist data, 13% of staff member data, and 17% of parent data) without adequate explanation.

OUTCOMES MEASURED: Tympanic temperature and symptom questionnaires (mood, wellness/illness, drooling, sleep, diarrhea/constipation, strong diapers, rashes, and flushing) were compared on toothdays and non-toothdays. A questionnaire was also given to parents at the end of the study that assessed their beliefs about which symptoms their child experienced.

RESULTS: Over the 7 months of the study, 2067 days of data were collected. There were 90 tooth eruptions, 236 toothdays, and 895 non-toothdays recorded. There was no statistically significant difference found in tympanic temperature when comparing toothdays to non-toothdays. Of the 32 separate analyses of symptoms that were performed, only parent-reported diarrhea was associated with tooth eruption (odds ratio=1.86; 95% confidence interval, 1.26-2.73). However, this association disappeared when looking at the 10 days leading up to an eruption or the 5 days on either side of an eruption and did not exist as reported by childcare staff. Children with fever or most other symptoms tended to be younger, suggesting that age could potentially confound any observed relationship between tooth eruptions and symptoms. In the final questionnaire, all parents retrospectively reported that their child suffered a variety of teething symptoms.

BACKGROUND: Parents and clinicians have traditionally attributed to teething many symptoms, such as fever, pain, irritability, diarrhea, drooling, and sleep disturbance. However, little evidence exists to support this claim. The authors investigated the relationship between tooth eruption, fever, and teething symptoms.

POPULATION STUDIED: All children aged 6 months to 2 years from 3 Australian daycare centers were eligible for the study if they attended at least 3 days a week. Twenty-one children (78% of eligible children) participated (mean age=14.4 months), and all completed the study.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study. Data on symptoms for each child were collected using questionnaires completed by parents each morning and by daycare center staff each afternoon over a 7-month period. A dental therapist examined each of the children daily over the same time period for signs of tooth eruption and measured each child’s temperature using an infrared tympanic thermometer. Tooth eruptions were defined as the first day a tooth edge emerged from the oral mucosa and remained consistently visible. Toothdays were defined as the 5 days leading up to a tooth eruption. Non-toothdays were defined as days more than 28 days clear of an eruption. Data were compared by logistic regression analysis. The study was limited in several ways. The small sample size may have affected the power of the study to detect small but clinically significant differences. There was an attempt at blinding the participants and their parents to the purpose of the study, but this blinding was incomplete and was lost over time. Parents and daycare staff might have been inclined to over-report symptoms if a child was having a tooth eruption. There was no mention made in the study of parental administration of antipyretic or analgesic medication that may have been used to treat symptoms. Use of such medications might have affected temperature readings or the results of daycare staff questionnaires. Also, tympanic temperature readings have been found inaccurate for detecting fever compared with core temperature readings. Finally, a substantial portion of data was missing from the report (6% of dental therapist data, 13% of staff member data, and 17% of parent data) without adequate explanation.

OUTCOMES MEASURED: Tympanic temperature and symptom questionnaires (mood, wellness/illness, drooling, sleep, diarrhea/constipation, strong diapers, rashes, and flushing) were compared on toothdays and non-toothdays. A questionnaire was also given to parents at the end of the study that assessed their beliefs about which symptoms their child experienced.

RESULTS: Over the 7 months of the study, 2067 days of data were collected. There were 90 tooth eruptions, 236 toothdays, and 895 non-toothdays recorded. There was no statistically significant difference found in tympanic temperature when comparing toothdays to non-toothdays. Of the 32 separate analyses of symptoms that were performed, only parent-reported diarrhea was associated with tooth eruption (odds ratio=1.86; 95% confidence interval, 1.26-2.73). However, this association disappeared when looking at the 10 days leading up to an eruption or the 5 days on either side of an eruption and did not exist as reported by childcare staff. Children with fever or most other symptoms tended to be younger, suggesting that age could potentially confound any observed relationship between tooth eruptions and symptoms. In the final questionnaire, all parents retrospectively reported that their child suffered a variety of teething symptoms.

BACKGROUND: Parents and clinicians have traditionally attributed to teething many symptoms, such as fever, pain, irritability, diarrhea, drooling, and sleep disturbance. However, little evidence exists to support this claim. The authors investigated the relationship between tooth eruption, fever, and teething symptoms.

POPULATION STUDIED: All children aged 6 months to 2 years from 3 Australian daycare centers were eligible for the study if they attended at least 3 days a week. Twenty-one children (78% of eligible children) participated (mean age=14.4 months), and all completed the study.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study. Data on symptoms for each child were collected using questionnaires completed by parents each morning and by daycare center staff each afternoon over a 7-month period. A dental therapist examined each of the children daily over the same time period for signs of tooth eruption and measured each child’s temperature using an infrared tympanic thermometer. Tooth eruptions were defined as the first day a tooth edge emerged from the oral mucosa and remained consistently visible. Toothdays were defined as the 5 days leading up to a tooth eruption. Non-toothdays were defined as days more than 28 days clear of an eruption. Data were compared by logistic regression analysis. The study was limited in several ways. The small sample size may have affected the power of the study to detect small but clinically significant differences. There was an attempt at blinding the participants and their parents to the purpose of the study, but this blinding was incomplete and was lost over time. Parents and daycare staff might have been inclined to over-report symptoms if a child was having a tooth eruption. There was no mention made in the study of parental administration of antipyretic or analgesic medication that may have been used to treat symptoms. Use of such medications might have affected temperature readings or the results of daycare staff questionnaires. Also, tympanic temperature readings have been found inaccurate for detecting fever compared with core temperature readings. Finally, a substantial portion of data was missing from the report (6% of dental therapist data, 13% of staff member data, and 17% of parent data) without adequate explanation.

OUTCOMES MEASURED: Tympanic temperature and symptom questionnaires (mood, wellness/illness, drooling, sleep, diarrhea/constipation, strong diapers, rashes, and flushing) were compared on toothdays and non-toothdays. A questionnaire was also given to parents at the end of the study that assessed their beliefs about which symptoms their child experienced.

RESULTS: Over the 7 months of the study, 2067 days of data were collected. There were 90 tooth eruptions, 236 toothdays, and 895 non-toothdays recorded. There was no statistically significant difference found in tympanic temperature when comparing toothdays to non-toothdays. Of the 32 separate analyses of symptoms that were performed, only parent-reported diarrhea was associated with tooth eruption (odds ratio=1.86; 95% confidence interval, 1.26-2.73). However, this association disappeared when looking at the 10 days leading up to an eruption or the 5 days on either side of an eruption and did not exist as reported by childcare staff. Children with fever or most other symptoms tended to be younger, suggesting that age could potentially confound any observed relationship between tooth eruptions and symptoms. In the final questionnaire, all parents retrospectively reported that their child suffered a variety of teething symptoms.

BACKGROUND: The adverse gastrointestinal effects of older nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are well documented. These effects are attributed to the drugs’ inhibition of cyclooxygenase-1 (COX-1), which is found in the gastrointestinal tract. The newer NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) have been shown to cause fewer endoscopically proven gastrointestinal erosions/ulcerations than nonselective NSAIDs that inhibit both COX-1 and COX-2. This disease-oriented evidence leads to concern about whether selective NSAIDs are really safer in the clinical setting than nonselective NSAIDs. This study attempts to answer the following question: Does rofecoxib, a selective COX-2 NSAID, lead to fewer clinically significant gastrointestinal events than naproxen, a nonselective NSAID?

POPULATION STUDIED: Patients were aged 50 years or older with rheumatoid arthritis (or 40 years or older with rheumatoid arthritis and taking long-term glucocorticoids) and were expected to be taking an NSAID for at least 1 year. Patients were recruited from 301 centers in 22 countries.

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded controlled trial. In general it was a well-designed study with no major flaws. The randomization process and the steps taken to conceal the treatment assignment were not described in detail. A total of 8076 patients were initially assigned to either 50 mg of rofecoxib once daily or 500 mg of naproxen twice daily. Patients were not allowed to take other NSAIDs but could take antacids and H2-receptor antagonists. Median follow-up was 9.0 months. Patients were followed until the study ended even if they stopped taking the study medications. Only 71.1% of the patients continued to take their assigned medication until the end of the study. Rates of discontinuation (29.3% for rofecoxib, 28.5% for naproxen), discontinuation for adverse events (16.4% and 16.1%, respectively), and discontinuation for lack of efficacy (6.3% and 6.5%, respectively) were similar between the groups. A committee using preset criteria and blinded to the treatment assessed the end points.

OUTCOMES MEASURED: Two outcomes were measured: the total number of gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer) and the number of complicated events (perforation, obstruction, and severe upper gastrointestinal bleeding). Also, the effectiveness of medication in reducing disease activity was measured using the Global Assessment of Disease Activity questionnaire. Finally, all episodes of confirmed and unconfirmed gastrointestinal bleeding were analyzed.

RESULTS: The risk of a gastrointestinal event was lower for patients receiving rofecoxib for the year of the study period (2.1 vs 4.5 events per 100 patient years, number needed to treat [NNT]=42). The risk of a complicated event was also lower for patients receiving rofecoxib (0.6 vs 1.6 events per 100 patient years, NNT=100). Overall mortality between the 2 groups was similar. Both drugs were equally effective in relieving the symptoms of rheumatoid arthritis. Of note, the rate of myocardial infarction was lower in the rofecoxib groups (0.1%) than in the naproxen group (0.4%); however, the mortality rates from cardiovascular causes were similar between the 2 groups. The difference in the rate of myocardial infarctions has been attributed to the antiplatelet effect (related to COX-1) of traditional NSAIDs, which the selective NSAIDs do not possess.

BACKGROUND: The adverse gastrointestinal effects of older nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are well documented. These effects are attributed to the drugs’ inhibition of cyclooxygenase-1 (COX-1), which is found in the gastrointestinal tract. The newer NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) have been shown to cause fewer endoscopically proven gastrointestinal erosions/ulcerations than nonselective NSAIDs that inhibit both COX-1 and COX-2. This disease-oriented evidence leads to concern about whether selective NSAIDs are really safer in the clinical setting than nonselective NSAIDs. This study attempts to answer the following question: Does rofecoxib, a selective COX-2 NSAID, lead to fewer clinically significant gastrointestinal events than naproxen, a nonselective NSAID?

POPULATION STUDIED: Patients were aged 50 years or older with rheumatoid arthritis (or 40 years or older with rheumatoid arthritis and taking long-term glucocorticoids) and were expected to be taking an NSAID for at least 1 year. Patients were recruited from 301 centers in 22 countries.

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded controlled trial. In general it was a well-designed study with no major flaws. The randomization process and the steps taken to conceal the treatment assignment were not described in detail. A total of 8076 patients were initially assigned to either 50 mg of rofecoxib once daily or 500 mg of naproxen twice daily. Patients were not allowed to take other NSAIDs but could take antacids and H2-receptor antagonists. Median follow-up was 9.0 months. Patients were followed until the study ended even if they stopped taking the study medications. Only 71.1% of the patients continued to take their assigned medication until the end of the study. Rates of discontinuation (29.3% for rofecoxib, 28.5% for naproxen), discontinuation for adverse events (16.4% and 16.1%, respectively), and discontinuation for lack of efficacy (6.3% and 6.5%, respectively) were similar between the groups. A committee using preset criteria and blinded to the treatment assessed the end points.

OUTCOMES MEASURED: Two outcomes were measured: the total number of gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer) and the number of complicated events (perforation, obstruction, and severe upper gastrointestinal bleeding). Also, the effectiveness of medication in reducing disease activity was measured using the Global Assessment of Disease Activity questionnaire. Finally, all episodes of confirmed and unconfirmed gastrointestinal bleeding were analyzed.

RESULTS: The risk of a gastrointestinal event was lower for patients receiving rofecoxib for the year of the study period (2.1 vs 4.5 events per 100 patient years, number needed to treat [NNT]=42). The risk of a complicated event was also lower for patients receiving rofecoxib (0.6 vs 1.6 events per 100 patient years, NNT=100). Overall mortality between the 2 groups was similar. Both drugs were equally effective in relieving the symptoms of rheumatoid arthritis. Of note, the rate of myocardial infarction was lower in the rofecoxib groups (0.1%) than in the naproxen group (0.4%); however, the mortality rates from cardiovascular causes were similar between the 2 groups. The difference in the rate of myocardial infarctions has been attributed to the antiplatelet effect (related to COX-1) of traditional NSAIDs, which the selective NSAIDs do not possess.

BACKGROUND: The adverse gastrointestinal effects of older nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are well documented. These effects are attributed to the drugs’ inhibition of cyclooxygenase-1 (COX-1), which is found in the gastrointestinal tract. The newer NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) have been shown to cause fewer endoscopically proven gastrointestinal erosions/ulcerations than nonselective NSAIDs that inhibit both COX-1 and COX-2. This disease-oriented evidence leads to concern about whether selective NSAIDs are really safer in the clinical setting than nonselective NSAIDs. This study attempts to answer the following question: Does rofecoxib, a selective COX-2 NSAID, lead to fewer clinically significant gastrointestinal events than naproxen, a nonselective NSAID?

POPULATION STUDIED: Patients were aged 50 years or older with rheumatoid arthritis (or 40 years or older with rheumatoid arthritis and taking long-term glucocorticoids) and were expected to be taking an NSAID for at least 1 year. Patients were recruited from 301 centers in 22 countries.

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded controlled trial. In general it was a well-designed study with no major flaws. The randomization process and the steps taken to conceal the treatment assignment were not described in detail. A total of 8076 patients were initially assigned to either 50 mg of rofecoxib once daily or 500 mg of naproxen twice daily. Patients were not allowed to take other NSAIDs but could take antacids and H2-receptor antagonists. Median follow-up was 9.0 months. Patients were followed until the study ended even if they stopped taking the study medications. Only 71.1% of the patients continued to take their assigned medication until the end of the study. Rates of discontinuation (29.3% for rofecoxib, 28.5% for naproxen), discontinuation for adverse events (16.4% and 16.1%, respectively), and discontinuation for lack of efficacy (6.3% and 6.5%, respectively) were similar between the groups. A committee using preset criteria and blinded to the treatment assessed the end points.

OUTCOMES MEASURED: Two outcomes were measured: the total number of gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer) and the number of complicated events (perforation, obstruction, and severe upper gastrointestinal bleeding). Also, the effectiveness of medication in reducing disease activity was measured using the Global Assessment of Disease Activity questionnaire. Finally, all episodes of confirmed and unconfirmed gastrointestinal bleeding were analyzed.

RESULTS: The risk of a gastrointestinal event was lower for patients receiving rofecoxib for the year of the study period (2.1 vs 4.5 events per 100 patient years, number needed to treat [NNT]=42). The risk of a complicated event was also lower for patients receiving rofecoxib (0.6 vs 1.6 events per 100 patient years, NNT=100). Overall mortality between the 2 groups was similar. Both drugs were equally effective in relieving the symptoms of rheumatoid arthritis. Of note, the rate of myocardial infarction was lower in the rofecoxib groups (0.1%) than in the naproxen group (0.4%); however, the mortality rates from cardiovascular causes were similar between the 2 groups. The difference in the rate of myocardial infarctions has been attributed to the antiplatelet effect (related to COX-1) of traditional NSAIDs, which the selective NSAIDs do not possess.

BACKGROUND: Discontinuation of benzodiazepines in patients on long-term treatment may be associated with restlessness, agitation, increased anxiety, insomnia, irritability, palpitations, and many other troublesome symptoms. Thus, patients with anxiety disorders taking long-term benzodiazepine therapy have difficulty successfully discontinuing treatment. Approaches to discontinuation include a gradual taper, cognitive-behavioral therapy, and adjunctive pharmacologic treatment.

POPULATION STUDIED: A total of 107 adult patients with generalized anxiety disorder were recruited from physician offices and by notices in the media. The patients had taken benzodiazepines for an average of 8.5 years (range=1-31 years); 91% had previously attempted discontinuation (average=3.4 attempts). Interestingly, only 24% of the patients were satisfied with their benzodiazepine therapy. The mean age was 48 years (range=22-77 years); 45% were women. All were treated at a psychopharmacology research unit and returned to the care of their family physicians at the end of the study.

STUDY DESIGN AND VALIDITY: After 2 to 4 weeks taking a steady dose of their benzodiazepine, the patients were assigned to receive double-blind treatment with imipramine 25 mg, buspirone 5 mg, or placebo. Each study drug was titrated over 2 weeks to a goal of 6 capsules daily in divided doses. After 4 weeks of concomitant treatment with a benzodiazepine and assigned study drug, the benzodiazepine dose was tapered by approximately 25% each week for 4 to 6 weeks. This taper was followed by a 5-week benzodiazepine-free phase; treatment was continued for 3 weeks followed by 2 weeks of placebo treatment. Patients were monitored weekly for withdrawal symptoms, anxiety, and depression. There are several limitations in the validity of this study. There is no mention of the method of randomization or of concealed allocation of study patients. Thirty-two patients (30%) did not complete the taper phase, and these patients were not all accounted for, that is, there was no intention-to-treat analysis. Additionally, the total number of patients remaining in each treatment arm was small, and the study may not have been large enough to find differences if they actually exist. Also, there was no comparison of demographics or clinical characteristics of the 3 treatment groups.

OUTCOMES MEASURED: The main outcomes measured were: (1) whether the taper was successful as defined by a benzodiazepine-free state at 12 weeks post-taper and (2) severity of symptoms of benzodiazepine discontinuation as rated by both physicians and patients.

RESULTS: At 3 months after benzodiazepine discontinuation, 82.5% of the imipramine-treated patients were benzodiazepine-free compared with 37.5% of the placebo-treated patients (P >.01; number needed to treat=2). Buspirone was less effective, and the success rate was not statistically different from placebo. However, the severity of withdrawal symptoms was worse in the imipramine-treated patients than with the buspirone- and placebo-treated patients (16.6 vs 8.9 and 10.4, respectively) on the 38-item physician-rated checklist (P >.03). Similar results were obtained using the patient-rated checklist, although these results were not shown. Dry mouth occurred significantly more frequently in imipramine-treated patients than in buspirone- and placebo-treated patients (number needed to harm=2).

BACKGROUND: Discontinuation of benzodiazepines in patients on long-term treatment may be associated with restlessness, agitation, increased anxiety, insomnia, irritability, palpitations, and many other troublesome symptoms. Thus, patients with anxiety disorders taking long-term benzodiazepine therapy have difficulty successfully discontinuing treatment. Approaches to discontinuation include a gradual taper, cognitive-behavioral therapy, and adjunctive pharmacologic treatment.

POPULATION STUDIED: A total of 107 adult patients with generalized anxiety disorder were recruited from physician offices and by notices in the media. The patients had taken benzodiazepines for an average of 8.5 years (range=1-31 years); 91% had previously attempted discontinuation (average=3.4 attempts). Interestingly, only 24% of the patients were satisfied with their benzodiazepine therapy. The mean age was 48 years (range=22-77 years); 45% were women. All were treated at a psychopharmacology research unit and returned to the care of their family physicians at the end of the study.

STUDY DESIGN AND VALIDITY: After 2 to 4 weeks taking a steady dose of their benzodiazepine, the patients were assigned to receive double-blind treatment with imipramine 25 mg, buspirone 5 mg, or placebo. Each study drug was titrated over 2 weeks to a goal of 6 capsules daily in divided doses. After 4 weeks of concomitant treatment with a benzodiazepine and assigned study drug, the benzodiazepine dose was tapered by approximately 25% each week for 4 to 6 weeks. This taper was followed by a 5-week benzodiazepine-free phase; treatment was continued for 3 weeks followed by 2 weeks of placebo treatment. Patients were monitored weekly for withdrawal symptoms, anxiety, and depression. There are several limitations in the validity of this study. There is no mention of the method of randomization or of concealed allocation of study patients. Thirty-two patients (30%) did not complete the taper phase, and these patients were not all accounted for, that is, there was no intention-to-treat analysis. Additionally, the total number of patients remaining in each treatment arm was small, and the study may not have been large enough to find differences if they actually exist. Also, there was no comparison of demographics or clinical characteristics of the 3 treatment groups.

OUTCOMES MEASURED: The main outcomes measured were: (1) whether the taper was successful as defined by a benzodiazepine-free state at 12 weeks post-taper and (2) severity of symptoms of benzodiazepine discontinuation as rated by both physicians and patients.

RESULTS: At 3 months after benzodiazepine discontinuation, 82.5% of the imipramine-treated patients were benzodiazepine-free compared with 37.5% of the placebo-treated patients (P >.01; number needed to treat=2). Buspirone was less effective, and the success rate was not statistically different from placebo. However, the severity of withdrawal symptoms was worse in the imipramine-treated patients than with the buspirone- and placebo-treated patients (16.6 vs 8.9 and 10.4, respectively) on the 38-item physician-rated checklist (P >.03). Similar results were obtained using the patient-rated checklist, although these results were not shown. Dry mouth occurred significantly more frequently in imipramine-treated patients than in buspirone- and placebo-treated patients (number needed to harm=2).

BACKGROUND: Discontinuation of benzodiazepines in patients on long-term treatment may be associated with restlessness, agitation, increased anxiety, insomnia, irritability, palpitations, and many other troublesome symptoms. Thus, patients with anxiety disorders taking long-term benzodiazepine therapy have difficulty successfully discontinuing treatment. Approaches to discontinuation include a gradual taper, cognitive-behavioral therapy, and adjunctive pharmacologic treatment.

POPULATION STUDIED: A total of 107 adult patients with generalized anxiety disorder were recruited from physician offices and by notices in the media. The patients had taken benzodiazepines for an average of 8.5 years (range=1-31 years); 91% had previously attempted discontinuation (average=3.4 attempts). Interestingly, only 24% of the patients were satisfied with their benzodiazepine therapy. The mean age was 48 years (range=22-77 years); 45% were women. All were treated at a psychopharmacology research unit and returned to the care of their family physicians at the end of the study.

STUDY DESIGN AND VALIDITY: After 2 to 4 weeks taking a steady dose of their benzodiazepine, the patients were assigned to receive double-blind treatment with imipramine 25 mg, buspirone 5 mg, or placebo. Each study drug was titrated over 2 weeks to a goal of 6 capsules daily in divided doses. After 4 weeks of concomitant treatment with a benzodiazepine and assigned study drug, the benzodiazepine dose was tapered by approximately 25% each week for 4 to 6 weeks. This taper was followed by a 5-week benzodiazepine-free phase; treatment was continued for 3 weeks followed by 2 weeks of placebo treatment. Patients were monitored weekly for withdrawal symptoms, anxiety, and depression. There are several limitations in the validity of this study. There is no mention of the method of randomization or of concealed allocation of study patients. Thirty-two patients (30%) did not complete the taper phase, and these patients were not all accounted for, that is, there was no intention-to-treat analysis. Additionally, the total number of patients remaining in each treatment arm was small, and the study may not have been large enough to find differences if they actually exist. Also, there was no comparison of demographics or clinical characteristics of the 3 treatment groups.

OUTCOMES MEASURED: The main outcomes measured were: (1) whether the taper was successful as defined by a benzodiazepine-free state at 12 weeks post-taper and (2) severity of symptoms of benzodiazepine discontinuation as rated by both physicians and patients.

RESULTS: At 3 months after benzodiazepine discontinuation, 82.5% of the imipramine-treated patients were benzodiazepine-free compared with 37.5% of the placebo-treated patients (P >.01; number needed to treat=2). Buspirone was less effective, and the success rate was not statistically different from placebo. However, the severity of withdrawal symptoms was worse in the imipramine-treated patients than with the buspirone- and placebo-treated patients (16.6 vs 8.9 and 10.4, respectively) on the 38-item physician-rated checklist (P >.03). Similar results were obtained using the patient-rated checklist, although these results were not shown. Dry mouth occurred significantly more frequently in imipramine-treated patients than in buspirone- and placebo-treated patients (number needed to harm=2).

BACKGROUND: Sore throat is a common complaint, with causes that include viruses and group A b-hemolytic streptococcus. Untreated pharyngitis due to this latter organism can lead to serious sequelae, such as peritonsillar abscess and rheumatic fever. A quick and accurate diagnosis, therefore, is important. Despite its relatively high prevalence among patients with pharyngitis, always performing a diagnostic laboratory test to uncover group A streptococcus is both impractical and costly. Identifying clinical correlates of strep throat would be useful.

POPULATION STUDIED: Adult and pediatric outpatients presenting with sore throat were studied.

STUDY DESIGN AND VALIDITY: The authors performed a thorough MEDLINE search to identify and systematically review studies of the diagnosis of group A b-hemolytic streptococcal pharyngitis in patients presenting with sore throat. Unpublished data were not sought. Initially 917 articles were identified, of which 9 met level I evidence criteria (large blinded prospective studies using throat culture as the reference standard). Pairs of authors reviewed each study, and discrepancies were resolved by discussion. The authors then pooled data to calculate the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of various history and physical examination elements. The authors only included studies with 300 or more subjects. Based on this threshold, 8 studies (1182 patients) were excluded from the pooled analysis.

OUTCOMES MEASURED: Primary outcomes measured included the sensitivity, specificity, LR+, and LR- of different clinical features.

RESULTS: The presence of tonsillar exudate or, pharyngeal exudate and a history of streptococcus exposure in the previous 2 weeks were most useful in predicting current streptococcus pharyngitis (LR+ = 3.4, 2.1, and 1.9, respectively). The absence of tender anterior cervical lymph nodes, tonsillar enlargement, and tonsillar or pharyngeal exudate was most useful in ruling out strep throat (LR- = 0.60, 0.63, and 0.74, respectively).

BACKGROUND: Sore throat is a common complaint, with causes that include viruses and group A b-hemolytic streptococcus. Untreated pharyngitis due to this latter organism can lead to serious sequelae, such as peritonsillar abscess and rheumatic fever. A quick and accurate diagnosis, therefore, is important. Despite its relatively high prevalence among patients with pharyngitis, always performing a diagnostic laboratory test to uncover group A streptococcus is both impractical and costly. Identifying clinical correlates of strep throat would be useful.

POPULATION STUDIED: Adult and pediatric outpatients presenting with sore throat were studied.

STUDY DESIGN AND VALIDITY: The authors performed a thorough MEDLINE search to identify and systematically review studies of the diagnosis of group A b-hemolytic streptococcal pharyngitis in patients presenting with sore throat. Unpublished data were not sought. Initially 917 articles were identified, of which 9 met level I evidence criteria (large blinded prospective studies using throat culture as the reference standard). Pairs of authors reviewed each study, and discrepancies were resolved by discussion. The authors then pooled data to calculate the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of various history and physical examination elements. The authors only included studies with 300 or more subjects. Based on this threshold, 8 studies (1182 patients) were excluded from the pooled analysis.

OUTCOMES MEASURED: Primary outcomes measured included the sensitivity, specificity, LR+, and LR- of different clinical features.

RESULTS: The presence of tonsillar exudate or, pharyngeal exudate and a history of streptococcus exposure in the previous 2 weeks were most useful in predicting current streptococcus pharyngitis (LR+ = 3.4, 2.1, and 1.9, respectively). The absence of tender anterior cervical lymph nodes, tonsillar enlargement, and tonsillar or pharyngeal exudate was most useful in ruling out strep throat (LR- = 0.60, 0.63, and 0.74, respectively).

BACKGROUND: Sore throat is a common complaint, with causes that include viruses and group A b-hemolytic streptococcus. Untreated pharyngitis due to this latter organism can lead to serious sequelae, such as peritonsillar abscess and rheumatic fever. A quick and accurate diagnosis, therefore, is important. Despite its relatively high prevalence among patients with pharyngitis, always performing a diagnostic laboratory test to uncover group A streptococcus is both impractical and costly. Identifying clinical correlates of strep throat would be useful.

POPULATION STUDIED: Adult and pediatric outpatients presenting with sore throat were studied.

STUDY DESIGN AND VALIDITY: The authors performed a thorough MEDLINE search to identify and systematically review studies of the diagnosis of group A b-hemolytic streptococcal pharyngitis in patients presenting with sore throat. Unpublished data were not sought. Initially 917 articles were identified, of which 9 met level I evidence criteria (large blinded prospective studies using throat culture as the reference standard). Pairs of authors reviewed each study, and discrepancies were resolved by discussion. The authors then pooled data to calculate the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of various history and physical examination elements. The authors only included studies with 300 or more subjects. Based on this threshold, 8 studies (1182 patients) were excluded from the pooled analysis.

OUTCOMES MEASURED: Primary outcomes measured included the sensitivity, specificity, LR+, and LR- of different clinical features.

RESULTS: The presence of tonsillar exudate or, pharyngeal exudate and a history of streptococcus exposure in the previous 2 weeks were most useful in predicting current streptococcus pharyngitis (LR+ = 3.4, 2.1, and 1.9, respectively). The absence of tender anterior cervical lymph nodes, tonsillar enlargement, and tonsillar or pharyngeal exudate was most useful in ruling out strep throat (LR- = 0.60, 0.63, and 0.74, respectively).

BACKGROUND: Pentoxifylline and cilostazol are the only 2 prescription drugs labeled for treatment of intermittent claudication. No studies have compared the relative benefit of these agents. The only other therapy demonstrated to be effective is active exercise intervention, usually in the form of a walking program.

POPULATION STUDIED: The investigators enrolled 698 patients with stable moderate to severe symptoms of intermittent claudication and confirmed peripheral vascular disease. These patients had symptoms present for at least 6 months but without substantial change in the last 3 months. All patients had peripheral vascular disease confirmed by either a resting ankle/brachial index of 0.90 or lower and a 10-mm Hg or higher decrease in ankle pressure measured 1 minute after walking to maximal walking distance, or a 20-mm Hg or higher decrease in postexercise ankle pressure in the symptomatic extremity. To qualify for study inclusion, the patients needed a baseline pain-free walking distance between 53.5 meters (1 minute on treadmill protocol) and 537.7 meters (10 minutes). The study subjects were 76% men and had an average age of 66 years. Patients were ineligible who had critical lower extremity ischemia, arterial reconstruction, or sympathectomy within the previous 3 months, as were patients with an exercise capacity limited by conditions other than intermittent claudication. The 3 groups were similar in age, sex, race, smoking status, diabetes, hypercholesterolemia, hypertension, and baseline disease severity.

STUDY DESIGN AND VALIDITY: The study was a double-blind multicenter trial with patients randomized using concealed allocation to receive either cilostazol (100 mg orally twice daily), pentoxifylline (400 mg orally 3 times daily), or placebo for a 24-week period. No specific counseling about diet, smoking cessation, or exercise was offered to the patients during the study period. At baseline and every 4 weeks afterward, study participants underwent evaluation including medical history, physical examination, treadmill testing, Doppler limb pressure measurements, and assessment of adverse events.

OUTCOMES MEASURED: The primary study end point was a comparison of the relative effects of cilostazol and pentoxifylline on walking ability, as measured by maximal walking distance on a standardized treadmill test. Secondary end points included pain-free walking distance and resting Doppler limb pressures. Perception of functional ability and quality of life was measured with the Medical Outcomes Scale Short Form-36 (SF-36) and the Walking Impairment Questionnaire. In addition, physicians and patients were asked for their subjective assessment of benefit at the end of treatment.

RESULTS: Using a treadmill protocol and assessed by intention-to treat analysis, cilostazol increased the maximal walking distance by 54% over baseline (average=107 m), compared with a 30% increase with pentoxifylline (P <.001) and a 34% increase in the placebo group (P <.001). The improvement with pentoxifylline was similar to that in the placebo group (average=65 m). Walking distances progressively increased in all 3 groups and did not plateau within the 24-week study. Side effects including headache, diarrhea, and abnormal stools occurred more commonly in the cilostazol group, yet the withdrawal rate was similar between the 2 active drug treatment groups (16%-19%). Scores on the SF-36 and the Walking Impairment Questionnaire revealed no significant differences in general health perception or patient-reported walking distance. In subjective assessment by patients, 51% of the cilostazol group judged their outcome to be successful compared with 39% in the pentoxifylline group (P=.004) and 34% in the placebo group (P <.001).

BACKGROUND: Pentoxifylline and cilostazol are the only 2 prescription drugs labeled for treatment of intermittent claudication. No studies have compared the relative benefit of these agents. The only other therapy demonstrated to be effective is active exercise intervention, usually in the form of a walking program.

POPULATION STUDIED: The investigators enrolled 698 patients with stable moderate to severe symptoms of intermittent claudication and confirmed peripheral vascular disease. These patients had symptoms present for at least 6 months but without substantial change in the last 3 months. All patients had peripheral vascular disease confirmed by either a resting ankle/brachial index of 0.90 or lower and a 10-mm Hg or higher decrease in ankle pressure measured 1 minute after walking to maximal walking distance, or a 20-mm Hg or higher decrease in postexercise ankle pressure in the symptomatic extremity. To qualify for study inclusion, the patients needed a baseline pain-free walking distance between 53.5 meters (1 minute on treadmill protocol) and 537.7 meters (10 minutes). The study subjects were 76% men and had an average age of 66 years. Patients were ineligible who had critical lower extremity ischemia, arterial reconstruction, or sympathectomy within the previous 3 months, as were patients with an exercise capacity limited by conditions other than intermittent claudication. The 3 groups were similar in age, sex, race, smoking status, diabetes, hypercholesterolemia, hypertension, and baseline disease severity.

STUDY DESIGN AND VALIDITY: The study was a double-blind multicenter trial with patients randomized using concealed allocation to receive either cilostazol (100 mg orally twice daily), pentoxifylline (400 mg orally 3 times daily), or placebo for a 24-week period. No specific counseling about diet, smoking cessation, or exercise was offered to the patients during the study period. At baseline and every 4 weeks afterward, study participants underwent evaluation including medical history, physical examination, treadmill testing, Doppler limb pressure measurements, and assessment of adverse events.

OUTCOMES MEASURED: The primary study end point was a comparison of the relative effects of cilostazol and pentoxifylline on walking ability, as measured by maximal walking distance on a standardized treadmill test. Secondary end points included pain-free walking distance and resting Doppler limb pressures. Perception of functional ability and quality of life was measured with the Medical Outcomes Scale Short Form-36 (SF-36) and the Walking Impairment Questionnaire. In addition, physicians and patients were asked for their subjective assessment of benefit at the end of treatment.

RESULTS: Using a treadmill protocol and assessed by intention-to treat analysis, cilostazol increased the maximal walking distance by 54% over baseline (average=107 m), compared with a 30% increase with pentoxifylline (P <.001) and a 34% increase in the placebo group (P <.001). The improvement with pentoxifylline was similar to that in the placebo group (average=65 m). Walking distances progressively increased in all 3 groups and did not plateau within the 24-week study. Side effects including headache, diarrhea, and abnormal stools occurred more commonly in the cilostazol group, yet the withdrawal rate was similar between the 2 active drug treatment groups (16%-19%). Scores on the SF-36 and the Walking Impairment Questionnaire revealed no significant differences in general health perception or patient-reported walking distance. In subjective assessment by patients, 51% of the cilostazol group judged their outcome to be successful compared with 39% in the pentoxifylline group (P=.004) and 34% in the placebo group (P <.001).

BACKGROUND: Pentoxifylline and cilostazol are the only 2 prescription drugs labeled for treatment of intermittent claudication. No studies have compared the relative benefit of these agents. The only other therapy demonstrated to be effective is active exercise intervention, usually in the form of a walking program.

POPULATION STUDIED: The investigators enrolled 698 patients with stable moderate to severe symptoms of intermittent claudication and confirmed peripheral vascular disease. These patients had symptoms present for at least 6 months but without substantial change in the last 3 months. All patients had peripheral vascular disease confirmed by either a resting ankle/brachial index of 0.90 or lower and a 10-mm Hg or higher decrease in ankle pressure measured 1 minute after walking to maximal walking distance, or a 20-mm Hg or higher decrease in postexercise ankle pressure in the symptomatic extremity. To qualify for study inclusion, the patients needed a baseline pain-free walking distance between 53.5 meters (1 minute on treadmill protocol) and 537.7 meters (10 minutes). The study subjects were 76% men and had an average age of 66 years. Patients were ineligible who had critical lower extremity ischemia, arterial reconstruction, or sympathectomy within the previous 3 months, as were patients with an exercise capacity limited by conditions other than intermittent claudication. The 3 groups were similar in age, sex, race, smoking status, diabetes, hypercholesterolemia, hypertension, and baseline disease severity.

STUDY DESIGN AND VALIDITY: The study was a double-blind multicenter trial with patients randomized using concealed allocation to receive either cilostazol (100 mg orally twice daily), pentoxifylline (400 mg orally 3 times daily), or placebo for a 24-week period. No specific counseling about diet, smoking cessation, or exercise was offered to the patients during the study period. At baseline and every 4 weeks afterward, study participants underwent evaluation including medical history, physical examination, treadmill testing, Doppler limb pressure measurements, and assessment of adverse events.

OUTCOMES MEASURED: The primary study end point was a comparison of the relative effects of cilostazol and pentoxifylline on walking ability, as measured by maximal walking distance on a standardized treadmill test. Secondary end points included pain-free walking distance and resting Doppler limb pressures. Perception of functional ability and quality of life was measured with the Medical Outcomes Scale Short Form-36 (SF-36) and the Walking Impairment Questionnaire. In addition, physicians and patients were asked for their subjective assessment of benefit at the end of treatment.

RESULTS: Using a treadmill protocol and assessed by intention-to treat analysis, cilostazol increased the maximal walking distance by 54% over baseline (average=107 m), compared with a 30% increase with pentoxifylline (P <.001) and a 34% increase in the placebo group (P <.001). The improvement with pentoxifylline was similar to that in the placebo group (average=65 m). Walking distances progressively increased in all 3 groups and did not plateau within the 24-week study. Side effects including headache, diarrhea, and abnormal stools occurred more commonly in the cilostazol group, yet the withdrawal rate was similar between the 2 active drug treatment groups (16%-19%). Scores on the SF-36 and the Walking Impairment Questionnaire revealed no significant differences in general health perception or patient-reported walking distance. In subjective assessment by patients, 51% of the cilostazol group judged their outcome to be successful compared with 39% in the pentoxifylline group (P=.004) and 34% in the placebo group (P <.001).