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Tubes for otitis media do not improve developmental outcomes
In young children with persistent otitis media with middle-ear effusions, the insertion of tympanostomy tubes does not improve cognitive, language, or speech development.
In young children with persistent otitis media with middle-ear effusions, the insertion of tympanostomy tubes does not improve cognitive, language, or speech development.
In young children with persistent otitis media with middle-ear effusions, the insertion of tympanostomy tubes does not improve cognitive, language, or speech development.
Detriments of tPA for acute stroke in routine clinical practice
Under optimal conditions, tissue plasminogen activator (tPA) may be a viable option for treatment of acute ischemic stroke; however, this study showed that protocol is not adhered to in practice and that these protocol deviations are associated with increased mortality and other adverse events. Based on these findings, tPA should not be used in routine clinical practice to treat acute stroke until individual hospitals develop protocols to guarantee the medication’s appropriate use.
Under optimal conditions, tissue plasminogen activator (tPA) may be a viable option for treatment of acute ischemic stroke; however, this study showed that protocol is not adhered to in practice and that these protocol deviations are associated with increased mortality and other adverse events. Based on these findings, tPA should not be used in routine clinical practice to treat acute stroke until individual hospitals develop protocols to guarantee the medication’s appropriate use.
Under optimal conditions, tissue plasminogen activator (tPA) may be a viable option for treatment of acute ischemic stroke; however, this study showed that protocol is not adhered to in practice and that these protocol deviations are associated with increased mortality and other adverse events. Based on these findings, tPA should not be used in routine clinical practice to treat acute stroke until individual hospitals develop protocols to guarantee the medication’s appropriate use.
How do calcium channel blockers compare with beta-blockers, diuretics, and angiotensin-converting enzyme inhibitors for hypertension?
ABSTRACT
BACKGROUND: Calcium channel blockers are used extensively in the treatment of hypertension. The authors systematically reviewed recent large, long-term trials that compared calcium channel blockers with beta-blockers or diuretics. A secondary analysis compared calcium channel blockers with ACE inhibitors in hypertensive patients with diabetes.
POPULATION STUDIED: The patients in this meta-analysis were pooled from 3 large European, multicenter studies (n = 21,611), that compared calcium channel blockers with diuretics or beta-blockers in elderly men and women with hypertension. A separate analysis included 3 smaller studies, bringing the total patients to 24,322. Most of these patients did not have active cardiovascular disease, including coronary artery disease and left ventricular hypertrophy; approximately 25% smoked; and approximately 50% had hypercholesterolemia. Only 1318 were included in a separate analysis of calcium channel blockers and ACE inhibitors in patients with hypertension and diabetes.
STUDY DESIGN AND VALIDITY: This was a meta-analysis of several randomized, controlled studies, which were double-blinded or assessed by a committee blinded to treatment assignment. Patients were followed for at least 2 years. The studies evaluated patients for major cardiovascular events, including myocardial infarction (MI), stroke, heart failure, and death. In the 3 major trials, target blood pressures were < 140/90 mm Hg, < 160/95 mm Hg, and < 90 mm Hg diastolic, respectively.
OUTCOMES MEASURED: The outcomes measured were fatal and nonfatal MI and stroke, development of congestive heart failure, and cardiovascular and total mortality.
RESULTS: Calcium channel blockers were associated with fewer nonfatal strokes than diuretics or beta-blockers (relative risk [RR]=0.751; 95% confidence interval [CI], 0.653-.864; absolute risk reduction [ARR]=0.9%; number needed to treat [NNT]=111). Fatal stroke rates were not different between the 2 groups (RR=0.918; 95% CI, 0.779-1.083). Also, there were fewer total strokes with calcium channel blockers (RR=0.869; 95% CI, 0.769-0.982; ARR=0.6%; NNT=167). Calcium channel blockers were associated with more nonfatal myocardial infarctions (RR=1.177; 95% CI, 1.011-1.370; absolute risk increase [ARI]=0.5%; number needed to harm [NNH]=200) and total myocardial infarctions (RR=1.182; 95% CI, 1.036-1.349; ARI=0.6%; NNH=167) compared with betablockers or diuretics. Rates of congestive heart failure, cardiovascular mortality, and total mortality were not different between the 2 groups.
Calcium channel blockers are associated with slightly fewer strokes and slightly more myocardial infarctions compared with beta-blockers or diuretics. No significant differences in total or cardiovascular mortality between the classes of medications were noted in this meta-analysis. These data support the notion that calcium channel blockers are as safe as, but no more effective than, conventional treatments for hypertension. In diabetic patients, an angiotensin-converting enzyme (ACE) inhibitor should be used before a calcium channel blocker. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared the calcium channel blocker amlodipine and the ACE inhibitor lisinopril with the diuretic chlorthalidone in 30,000 elderly patients with hypertension and 10,000 with comorbid diabetes. Results of ALLHAT should be available by fall 2002. Meanwhile, primarily because of high costs, calcium channel blockers should remain fourth-line agents in the treatment of hypertension, after diuretics, beta-blockers, and in diabetic patients particularly, ACE inhibitors.
ABSTRACT
BACKGROUND: Calcium channel blockers are used extensively in the treatment of hypertension. The authors systematically reviewed recent large, long-term trials that compared calcium channel blockers with beta-blockers or diuretics. A secondary analysis compared calcium channel blockers with ACE inhibitors in hypertensive patients with diabetes.
POPULATION STUDIED: The patients in this meta-analysis were pooled from 3 large European, multicenter studies (n = 21,611), that compared calcium channel blockers with diuretics or beta-blockers in elderly men and women with hypertension. A separate analysis included 3 smaller studies, bringing the total patients to 24,322. Most of these patients did not have active cardiovascular disease, including coronary artery disease and left ventricular hypertrophy; approximately 25% smoked; and approximately 50% had hypercholesterolemia. Only 1318 were included in a separate analysis of calcium channel blockers and ACE inhibitors in patients with hypertension and diabetes.
STUDY DESIGN AND VALIDITY: This was a meta-analysis of several randomized, controlled studies, which were double-blinded or assessed by a committee blinded to treatment assignment. Patients were followed for at least 2 years. The studies evaluated patients for major cardiovascular events, including myocardial infarction (MI), stroke, heart failure, and death. In the 3 major trials, target blood pressures were < 140/90 mm Hg, < 160/95 mm Hg, and < 90 mm Hg diastolic, respectively.
OUTCOMES MEASURED: The outcomes measured were fatal and nonfatal MI and stroke, development of congestive heart failure, and cardiovascular and total mortality.
RESULTS: Calcium channel blockers were associated with fewer nonfatal strokes than diuretics or beta-blockers (relative risk [RR]=0.751; 95% confidence interval [CI], 0.653-.864; absolute risk reduction [ARR]=0.9%; number needed to treat [NNT]=111). Fatal stroke rates were not different between the 2 groups (RR=0.918; 95% CI, 0.779-1.083). Also, there were fewer total strokes with calcium channel blockers (RR=0.869; 95% CI, 0.769-0.982; ARR=0.6%; NNT=167). Calcium channel blockers were associated with more nonfatal myocardial infarctions (RR=1.177; 95% CI, 1.011-1.370; absolute risk increase [ARI]=0.5%; number needed to harm [NNH]=200) and total myocardial infarctions (RR=1.182; 95% CI, 1.036-1.349; ARI=0.6%; NNH=167) compared with betablockers or diuretics. Rates of congestive heart failure, cardiovascular mortality, and total mortality were not different between the 2 groups.
Calcium channel blockers are associated with slightly fewer strokes and slightly more myocardial infarctions compared with beta-blockers or diuretics. No significant differences in total or cardiovascular mortality between the classes of medications were noted in this meta-analysis. These data support the notion that calcium channel blockers are as safe as, but no more effective than, conventional treatments for hypertension. In diabetic patients, an angiotensin-converting enzyme (ACE) inhibitor should be used before a calcium channel blocker. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared the calcium channel blocker amlodipine and the ACE inhibitor lisinopril with the diuretic chlorthalidone in 30,000 elderly patients with hypertension and 10,000 with comorbid diabetes. Results of ALLHAT should be available by fall 2002. Meanwhile, primarily because of high costs, calcium channel blockers should remain fourth-line agents in the treatment of hypertension, after diuretics, beta-blockers, and in diabetic patients particularly, ACE inhibitors.
ABSTRACT
BACKGROUND: Calcium channel blockers are used extensively in the treatment of hypertension. The authors systematically reviewed recent large, long-term trials that compared calcium channel blockers with beta-blockers or diuretics. A secondary analysis compared calcium channel blockers with ACE inhibitors in hypertensive patients with diabetes.
POPULATION STUDIED: The patients in this meta-analysis were pooled from 3 large European, multicenter studies (n = 21,611), that compared calcium channel blockers with diuretics or beta-blockers in elderly men and women with hypertension. A separate analysis included 3 smaller studies, bringing the total patients to 24,322. Most of these patients did not have active cardiovascular disease, including coronary artery disease and left ventricular hypertrophy; approximately 25% smoked; and approximately 50% had hypercholesterolemia. Only 1318 were included in a separate analysis of calcium channel blockers and ACE inhibitors in patients with hypertension and diabetes.
STUDY DESIGN AND VALIDITY: This was a meta-analysis of several randomized, controlled studies, which were double-blinded or assessed by a committee blinded to treatment assignment. Patients were followed for at least 2 years. The studies evaluated patients for major cardiovascular events, including myocardial infarction (MI), stroke, heart failure, and death. In the 3 major trials, target blood pressures were < 140/90 mm Hg, < 160/95 mm Hg, and < 90 mm Hg diastolic, respectively.
OUTCOMES MEASURED: The outcomes measured were fatal and nonfatal MI and stroke, development of congestive heart failure, and cardiovascular and total mortality.
RESULTS: Calcium channel blockers were associated with fewer nonfatal strokes than diuretics or beta-blockers (relative risk [RR]=0.751; 95% confidence interval [CI], 0.653-.864; absolute risk reduction [ARR]=0.9%; number needed to treat [NNT]=111). Fatal stroke rates were not different between the 2 groups (RR=0.918; 95% CI, 0.779-1.083). Also, there were fewer total strokes with calcium channel blockers (RR=0.869; 95% CI, 0.769-0.982; ARR=0.6%; NNT=167). Calcium channel blockers were associated with more nonfatal myocardial infarctions (RR=1.177; 95% CI, 1.011-1.370; absolute risk increase [ARI]=0.5%; number needed to harm [NNH]=200) and total myocardial infarctions (RR=1.182; 95% CI, 1.036-1.349; ARI=0.6%; NNH=167) compared with betablockers or diuretics. Rates of congestive heart failure, cardiovascular mortality, and total mortality were not different between the 2 groups.
Calcium channel blockers are associated with slightly fewer strokes and slightly more myocardial infarctions compared with beta-blockers or diuretics. No significant differences in total or cardiovascular mortality between the classes of medications were noted in this meta-analysis. These data support the notion that calcium channel blockers are as safe as, but no more effective than, conventional treatments for hypertension. In diabetic patients, an angiotensin-converting enzyme (ACE) inhibitor should be used before a calcium channel blocker. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared the calcium channel blocker amlodipine and the ACE inhibitor lisinopril with the diuretic chlorthalidone in 30,000 elderly patients with hypertension and 10,000 with comorbid diabetes. Results of ALLHAT should be available by fall 2002. Meanwhile, primarily because of high costs, calcium channel blockers should remain fourth-line agents in the treatment of hypertension, after diuretics, beta-blockers, and in diabetic patients particularly, ACE inhibitors.
Oseltamivir for Flu Prevention
CLINICAL QUESTION: Can oseltamivir be used to prevent influenza infection?
BACKGROUND: Oseltamivir reduces the replication of influenza A and B by inhibiting influenza neuraminidase, an essential enzyme involved in the final packaging of new viral particles. Rimantadine and amantadine have been used for prophylaxis but are only effective against influenza A; adverse effects and cost limit their use. Oseltamivir is currently indicated to treat acute influenza infection if given within the first 2 days of symptoms. The present study evaluated oseltamivir for the prevention of influenza in healthy persons.
POPULATION STUDIED: The researchers studied 1562 healthy subjects with a mean age of 35 years (range = 18 to 65 years); 63% were women. Key exclusion criteria included having had an influenza vaccination in the previous year or an acute respiratory illness accompanied by a fever in the week before drug administration. Patients with any indication for influenza immunization according to 1998 Centers for Disease Control (CDC) and Prevention guidelines were also excluded.
STUDY DESIGN AND VALIDITY: Two identical randomized placebo-controlled double-blinded multicenter studies were conducted. Because of a low incidence of influenza infection (38/1559, 2.4%), the investigators combined the data before unblinding. Subjects were started on oseltamivir or placebo following an increase in influenzavirus activity at the clinical site. They received either oseltamivir 75 mg once daily, 75 mg twice daily, or placebo for 6 weeks. Return visits occurred at weeks 3, 6, and 8. Participants were instructed to return to the clinic for influenzalike symptoms. Nasal and pharyngeal swabs were collected for influenzavirus culture when patients presented with illness. Influenza antibody testing was done at baseline and 8 weeks.
OUTCOMES MEASURED: The primary end point was laboratory-confirmed influenzalike illness during the 6-week period of drug administration. Influenzalike illness was defined as an oral temperature of Ž37.2°C, with at least one respiratory symptom (cough, sore throat, or nasal congestion) and at least one constitutional symptom (aches, fatigue, headache, or chills or sweats). Laboratory confirmation was defined as culture of influenzavirus or 4-fold increase in antibody titer.
RESULTS: The rates of laboratory-confirmed clinical influenza were significantly lower in the oseltamivir once-daily (6/520, 1.2%) and twice-daily (7/520, 1.3%) groups than in the placebo group (25/519, 4.8%). These differences were statistically significant (P <.001 and P = .001, respectively). The relative risk reduction for influenza of once and twice daily dosing were 76% (95% confidence interval [CI], 46-91) and 72% (95% CI, 40-89), respectively. The number needed to treat (NNT) to prevent one case of influenza is 29. Drop-out rates were low and did not differ between the groups (3.1% to 4.0%), suggesting that the medication was well tolerated. Compliance between the groups did not differ.
Oseltamivir has the ability to prevent influenza infection, but the real world utility of this agent for prophylaxis is limited. Using an estimate of $225 per 6-week course of 75 mg once daily and an NNT of 29, the cost of preventing one case of influenza with oseltamivir is $6525. In a similar unvaccinated healthy population, the average cost per person attributed to respirato ry illness (including influenza) has been estimated at $152.18 (1994 dollars) per flu season.1 This estimate includes time lost from work and physician visits. In the same study, it was found that the vaccination of healthy working adults saved $46.85 per person vaccinated. In a low-risk population, oseltamivir is unlikely to be cost-effective. Recent CDC guidelines state that all persons interested in decreasing their likelihood of becoming ill with influenza may be vaccinated.2 Whether oseltamivir is the agent of choice for rare instances requiring prophylaxis will require comparison with rimantadine. In an unvaccinated population at high risk during an influenza B outbreak, oseltamivir may offer protection. However this study only documented one case of influenza B in the 1559 study participants.
CLINICAL QUESTION: Can oseltamivir be used to prevent influenza infection?
BACKGROUND: Oseltamivir reduces the replication of influenza A and B by inhibiting influenza neuraminidase, an essential enzyme involved in the final packaging of new viral particles. Rimantadine and amantadine have been used for prophylaxis but are only effective against influenza A; adverse effects and cost limit their use. Oseltamivir is currently indicated to treat acute influenza infection if given within the first 2 days of symptoms. The present study evaluated oseltamivir for the prevention of influenza in healthy persons.
POPULATION STUDIED: The researchers studied 1562 healthy subjects with a mean age of 35 years (range = 18 to 65 years); 63% were women. Key exclusion criteria included having had an influenza vaccination in the previous year or an acute respiratory illness accompanied by a fever in the week before drug administration. Patients with any indication for influenza immunization according to 1998 Centers for Disease Control (CDC) and Prevention guidelines were also excluded.
STUDY DESIGN AND VALIDITY: Two identical randomized placebo-controlled double-blinded multicenter studies were conducted. Because of a low incidence of influenza infection (38/1559, 2.4%), the investigators combined the data before unblinding. Subjects were started on oseltamivir or placebo following an increase in influenzavirus activity at the clinical site. They received either oseltamivir 75 mg once daily, 75 mg twice daily, or placebo for 6 weeks. Return visits occurred at weeks 3, 6, and 8. Participants were instructed to return to the clinic for influenzalike symptoms. Nasal and pharyngeal swabs were collected for influenzavirus culture when patients presented with illness. Influenza antibody testing was done at baseline and 8 weeks.
OUTCOMES MEASURED: The primary end point was laboratory-confirmed influenzalike illness during the 6-week period of drug administration. Influenzalike illness was defined as an oral temperature of Ž37.2°C, with at least one respiratory symptom (cough, sore throat, or nasal congestion) and at least one constitutional symptom (aches, fatigue, headache, or chills or sweats). Laboratory confirmation was defined as culture of influenzavirus or 4-fold increase in antibody titer.
RESULTS: The rates of laboratory-confirmed clinical influenza were significantly lower in the oseltamivir once-daily (6/520, 1.2%) and twice-daily (7/520, 1.3%) groups than in the placebo group (25/519, 4.8%). These differences were statistically significant (P <.001 and P = .001, respectively). The relative risk reduction for influenza of once and twice daily dosing were 76% (95% confidence interval [CI], 46-91) and 72% (95% CI, 40-89), respectively. The number needed to treat (NNT) to prevent one case of influenza is 29. Drop-out rates were low and did not differ between the groups (3.1% to 4.0%), suggesting that the medication was well tolerated. Compliance between the groups did not differ.
Oseltamivir has the ability to prevent influenza infection, but the real world utility of this agent for prophylaxis is limited. Using an estimate of $225 per 6-week course of 75 mg once daily and an NNT of 29, the cost of preventing one case of influenza with oseltamivir is $6525. In a similar unvaccinated healthy population, the average cost per person attributed to respirato ry illness (including influenza) has been estimated at $152.18 (1994 dollars) per flu season.1 This estimate includes time lost from work and physician visits. In the same study, it was found that the vaccination of healthy working adults saved $46.85 per person vaccinated. In a low-risk population, oseltamivir is unlikely to be cost-effective. Recent CDC guidelines state that all persons interested in decreasing their likelihood of becoming ill with influenza may be vaccinated.2 Whether oseltamivir is the agent of choice for rare instances requiring prophylaxis will require comparison with rimantadine. In an unvaccinated population at high risk during an influenza B outbreak, oseltamivir may offer protection. However this study only documented one case of influenza B in the 1559 study participants.
CLINICAL QUESTION: Can oseltamivir be used to prevent influenza infection?
BACKGROUND: Oseltamivir reduces the replication of influenza A and B by inhibiting influenza neuraminidase, an essential enzyme involved in the final packaging of new viral particles. Rimantadine and amantadine have been used for prophylaxis but are only effective against influenza A; adverse effects and cost limit their use. Oseltamivir is currently indicated to treat acute influenza infection if given within the first 2 days of symptoms. The present study evaluated oseltamivir for the prevention of influenza in healthy persons.
POPULATION STUDIED: The researchers studied 1562 healthy subjects with a mean age of 35 years (range = 18 to 65 years); 63% were women. Key exclusion criteria included having had an influenza vaccination in the previous year or an acute respiratory illness accompanied by a fever in the week before drug administration. Patients with any indication for influenza immunization according to 1998 Centers for Disease Control (CDC) and Prevention guidelines were also excluded.
STUDY DESIGN AND VALIDITY: Two identical randomized placebo-controlled double-blinded multicenter studies were conducted. Because of a low incidence of influenza infection (38/1559, 2.4%), the investigators combined the data before unblinding. Subjects were started on oseltamivir or placebo following an increase in influenzavirus activity at the clinical site. They received either oseltamivir 75 mg once daily, 75 mg twice daily, or placebo for 6 weeks. Return visits occurred at weeks 3, 6, and 8. Participants were instructed to return to the clinic for influenzalike symptoms. Nasal and pharyngeal swabs were collected for influenzavirus culture when patients presented with illness. Influenza antibody testing was done at baseline and 8 weeks.
OUTCOMES MEASURED: The primary end point was laboratory-confirmed influenzalike illness during the 6-week period of drug administration. Influenzalike illness was defined as an oral temperature of Ž37.2°C, with at least one respiratory symptom (cough, sore throat, or nasal congestion) and at least one constitutional symptom (aches, fatigue, headache, or chills or sweats). Laboratory confirmation was defined as culture of influenzavirus or 4-fold increase in antibody titer.
RESULTS: The rates of laboratory-confirmed clinical influenza were significantly lower in the oseltamivir once-daily (6/520, 1.2%) and twice-daily (7/520, 1.3%) groups than in the placebo group (25/519, 4.8%). These differences were statistically significant (P <.001 and P = .001, respectively). The relative risk reduction for influenza of once and twice daily dosing were 76% (95% confidence interval [CI], 46-91) and 72% (95% CI, 40-89), respectively. The number needed to treat (NNT) to prevent one case of influenza is 29. Drop-out rates were low and did not differ between the groups (3.1% to 4.0%), suggesting that the medication was well tolerated. Compliance between the groups did not differ.
Oseltamivir has the ability to prevent influenza infection, but the real world utility of this agent for prophylaxis is limited. Using an estimate of $225 per 6-week course of 75 mg once daily and an NNT of 29, the cost of preventing one case of influenza with oseltamivir is $6525. In a similar unvaccinated healthy population, the average cost per person attributed to respirato ry illness (including influenza) has been estimated at $152.18 (1994 dollars) per flu season.1 This estimate includes time lost from work and physician visits. In the same study, it was found that the vaccination of healthy working adults saved $46.85 per person vaccinated. In a low-risk population, oseltamivir is unlikely to be cost-effective. Recent CDC guidelines state that all persons interested in decreasing their likelihood of becoming ill with influenza may be vaccinated.2 Whether oseltamivir is the agent of choice for rare instances requiring prophylaxis will require comparison with rimantadine. In an unvaccinated population at high risk during an influenza B outbreak, oseltamivir may offer protection. However this study only documented one case of influenza B in the 1559 study participants.