BACKGROUND: Interruption of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is renoprotective both in patients with type 1 diabetes and in patients without diabetes who have overt nephropathy. This study evaluates the effectiveness of losartan, an angiotensin-receptor blocker (ARB), in slowing the progression of nephropathy in type 2 diabetes.

POPULATION STUDIED: The Reduction of Endpoints in Non-insulin– dependent diabetes with the Angiotensin II Antagonist Losartan (RENAAL) study included 1513 people with type 2 diabetes and nephropathy, ranging in age from 31 to 70 years. Nephropathy was defined as urinary protein excretion of at least 500 mg daily and a serum creatinine of 1.3 to 3.0 mg per dL. Patients were excluded if they had a diagnosis of nondiabetic nephropathy; had experienced a recent myocardial infarction, transient ischemic attack, or stroke; had recently undergone coronary artery bypass grafting or percutaneous coronary angioplasty; or had ever had heart failure.

STUDY DESIGN AND VALIDITY: The RENAAL study was a double-blind randomized placebo-controlled trial in which patients were assigned to receive either losartan 50 to 100 mg or placebo. All patients received other antihypertensive therapy (excluding ACE inhibitors and ARBs) as necessary to maintain a blood pressure level of less than 140/90 mm Hg. The groups were similar at baseline, with a mean serum creatinine was 1.9 mg per dL (standard deviation = 0.5). The patients were followed up for a mean of 3.4 years, and an intention-to-treat analysis was reported. The study methods appeared valid, although concealment of allocation was not described.

OUTCOMES MEASURED: The primary outcome was the combined outcomes of a doubling of the baseline serum creatinine concentration, end-stage renal disease, and death.

RESULTS: Treatment with losartan resulted in a 16% reduction in the primary composite end point (95% confidence interval [CI], 2%-28%; P =.02; number needed to treat [NNT]=28). The risk for doubling of serum creatinine concentration was reduced by 25% (95% CI, 8-39; P =.006; NNT=23). The likelihood of reaching end-stage renal disease was reduced by 28% (95% CI, 11-42; P =.002; NNT=17). Losartan also decreased the level of proteinuria by 35% (P < .001) and the rate of decline of renal function by 18% (P =.01). A 32% reduction in a patient’s first hospitalization for heart failure was observed (P =.005). There was no difference in the composite end point of morbidity and mortality due to cardiovascular causes, adverse events, or overall mortality.

BACKGROUND: Interruption of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is renoprotective both in patients with type 1 diabetes and in patients without diabetes who have overt nephropathy. This study evaluates the effectiveness of losartan, an angiotensin-receptor blocker (ARB), in slowing the progression of nephropathy in type 2 diabetes.

POPULATION STUDIED: The Reduction of Endpoints in Non-insulin– dependent diabetes with the Angiotensin II Antagonist Losartan (RENAAL) study included 1513 people with type 2 diabetes and nephropathy, ranging in age from 31 to 70 years. Nephropathy was defined as urinary protein excretion of at least 500 mg daily and a serum creatinine of 1.3 to 3.0 mg per dL. Patients were excluded if they had a diagnosis of nondiabetic nephropathy; had experienced a recent myocardial infarction, transient ischemic attack, or stroke; had recently undergone coronary artery bypass grafting or percutaneous coronary angioplasty; or had ever had heart failure.

STUDY DESIGN AND VALIDITY: The RENAAL study was a double-blind randomized placebo-controlled trial in which patients were assigned to receive either losartan 50 to 100 mg or placebo. All patients received other antihypertensive therapy (excluding ACE inhibitors and ARBs) as necessary to maintain a blood pressure level of less than 140/90 mm Hg. The groups were similar at baseline, with a mean serum creatinine was 1.9 mg per dL (standard deviation = 0.5). The patients were followed up for a mean of 3.4 years, and an intention-to-treat analysis was reported. The study methods appeared valid, although concealment of allocation was not described.

OUTCOMES MEASURED: The primary outcome was the combined outcomes of a doubling of the baseline serum creatinine concentration, end-stage renal disease, and death.

RESULTS: Treatment with losartan resulted in a 16% reduction in the primary composite end point (95% confidence interval [CI], 2%-28%; P =.02; number needed to treat [NNT]=28). The risk for doubling of serum creatinine concentration was reduced by 25% (95% CI, 8-39; P =.006; NNT=23). The likelihood of reaching end-stage renal disease was reduced by 28% (95% CI, 11-42; P =.002; NNT=17). Losartan also decreased the level of proteinuria by 35% (P < .001) and the rate of decline of renal function by 18% (P =.01). A 32% reduction in a patient’s first hospitalization for heart failure was observed (P =.005). There was no difference in the composite end point of morbidity and mortality due to cardiovascular causes, adverse events, or overall mortality.

BACKGROUND: Interruption of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is renoprotective both in patients with type 1 diabetes and in patients without diabetes who have overt nephropathy. This study evaluates the effectiveness of losartan, an angiotensin-receptor blocker (ARB), in slowing the progression of nephropathy in type 2 diabetes.

POPULATION STUDIED: The Reduction of Endpoints in Non-insulin– dependent diabetes with the Angiotensin II Antagonist Losartan (RENAAL) study included 1513 people with type 2 diabetes and nephropathy, ranging in age from 31 to 70 years. Nephropathy was defined as urinary protein excretion of at least 500 mg daily and a serum creatinine of 1.3 to 3.0 mg per dL. Patients were excluded if they had a diagnosis of nondiabetic nephropathy; had experienced a recent myocardial infarction, transient ischemic attack, or stroke; had recently undergone coronary artery bypass grafting or percutaneous coronary angioplasty; or had ever had heart failure.

STUDY DESIGN AND VALIDITY: The RENAAL study was a double-blind randomized placebo-controlled trial in which patients were assigned to receive either losartan 50 to 100 mg or placebo. All patients received other antihypertensive therapy (excluding ACE inhibitors and ARBs) as necessary to maintain a blood pressure level of less than 140/90 mm Hg. The groups were similar at baseline, with a mean serum creatinine was 1.9 mg per dL (standard deviation = 0.5). The patients were followed up for a mean of 3.4 years, and an intention-to-treat analysis was reported. The study methods appeared valid, although concealment of allocation was not described.

OUTCOMES MEASURED: The primary outcome was the combined outcomes of a doubling of the baseline serum creatinine concentration, end-stage renal disease, and death.

RESULTS: Treatment with losartan resulted in a 16% reduction in the primary composite end point (95% confidence interval [CI], 2%-28%; P =.02; number needed to treat [NNT]=28). The risk for doubling of serum creatinine concentration was reduced by 25% (95% CI, 8-39; P =.006; NNT=23). The likelihood of reaching end-stage renal disease was reduced by 28% (95% CI, 11-42; P =.002; NNT=17). Losartan also decreased the level of proteinuria by 35% (P < .001) and the rate of decline of renal function by 18% (P =.01). A 32% reduction in a patient’s first hospitalization for heart failure was observed (P =.005). There was no difference in the composite end point of morbidity and mortality due to cardiovascular causes, adverse events, or overall mortality.

BACKGROUND: Urge urinary incontinence has drawn attention recently, with a number of studies looking at which treatment provides the best results with the fewest side effects. The authors of this study performed a meta-analysis comparing treatment outcomes and side effects for short-acting oxybutynin and tolterodine.

POPULATION STUDIED: The trials included in this meta-analysis studied patients older than 18 years and who were complaining of urge incontinence or an association of frequency (> 8 times per day) and urgency, or had received a diagnosis of detrusor instability. Patients were excluded who had used co-interventions within the 14 days preceding the trial. No further information was available on the populations studied, making it difficult to determine if the patients were similar to those of a primary care practice.

STUDY DESIGN AND VALIDITY: The authors conducted a rigorous literature search without language constraint for published and unpublished studies that were randomized or quasirandomized and double blinded comparing tolterodine with oxybutynin. At least one arm of each study needed to be randomized to 1 to 2 mg tolterodine twice daily and the other arm to 2.5 to 5 mg of oxybutynin 3 times daily. Two independent reviewers decided which trials would be considered in the analysis according to priori eligibility criteria.

OUTCOMES MEASURED: The primary outcomes included the number of incontinent episodes per 24-hour period, the quantity of pads used per 24 hours, the number of micturitions per 24 hours, and the mean voided volume per micturition. Secondary outcomes included the number of patients with side effects and withdrawals attributed to side effects, the number of patients changing dose, urologic measurements, and quality of life.

RESULTS: Oxybutynin produced a statistically and clinically significant decrease in the number of incontinent episodes per 24-hour period (weighted mean difference = 0.41; 95% confidence interval [CI], 0.04-0.77). Both drugs decreased the number of episodes, but the oxybutynin-treated group averaged 0.5 fewer episodes per day. Patients taking tolterodine reported significantly less dry mouth (relative risk [RR] = 0.54; 95% CI, 0.48-0.61) and less moderate to severe dry mouth (RR=0.33; 95% CI, 0.24-0.45). The risk of withdrawing from the study because of side effects was decreased by 37% in the tolterodine group (RR=0.63; 95% CI, 0.46-0.88).

BACKGROUND: Urge urinary incontinence has drawn attention recently, with a number of studies looking at which treatment provides the best results with the fewest side effects. The authors of this study performed a meta-analysis comparing treatment outcomes and side effects for short-acting oxybutynin and tolterodine.

POPULATION STUDIED: The trials included in this meta-analysis studied patients older than 18 years and who were complaining of urge incontinence or an association of frequency (> 8 times per day) and urgency, or had received a diagnosis of detrusor instability. Patients were excluded who had used co-interventions within the 14 days preceding the trial. No further information was available on the populations studied, making it difficult to determine if the patients were similar to those of a primary care practice.

STUDY DESIGN AND VALIDITY: The authors conducted a rigorous literature search without language constraint for published and unpublished studies that were randomized or quasirandomized and double blinded comparing tolterodine with oxybutynin. At least one arm of each study needed to be randomized to 1 to 2 mg tolterodine twice daily and the other arm to 2.5 to 5 mg of oxybutynin 3 times daily. Two independent reviewers decided which trials would be considered in the analysis according to priori eligibility criteria.

OUTCOMES MEASURED: The primary outcomes included the number of incontinent episodes per 24-hour period, the quantity of pads used per 24 hours, the number of micturitions per 24 hours, and the mean voided volume per micturition. Secondary outcomes included the number of patients with side effects and withdrawals attributed to side effects, the number of patients changing dose, urologic measurements, and quality of life.

RESULTS: Oxybutynin produced a statistically and clinically significant decrease in the number of incontinent episodes per 24-hour period (weighted mean difference = 0.41; 95% confidence interval [CI], 0.04-0.77). Both drugs decreased the number of episodes, but the oxybutynin-treated group averaged 0.5 fewer episodes per day. Patients taking tolterodine reported significantly less dry mouth (relative risk [RR] = 0.54; 95% CI, 0.48-0.61) and less moderate to severe dry mouth (RR=0.33; 95% CI, 0.24-0.45). The risk of withdrawing from the study because of side effects was decreased by 37% in the tolterodine group (RR=0.63; 95% CI, 0.46-0.88).

BACKGROUND: Urge urinary incontinence has drawn attention recently, with a number of studies looking at which treatment provides the best results with the fewest side effects. The authors of this study performed a meta-analysis comparing treatment outcomes and side effects for short-acting oxybutynin and tolterodine.

POPULATION STUDIED: The trials included in this meta-analysis studied patients older than 18 years and who were complaining of urge incontinence or an association of frequency (> 8 times per day) and urgency, or had received a diagnosis of detrusor instability. Patients were excluded who had used co-interventions within the 14 days preceding the trial. No further information was available on the populations studied, making it difficult to determine if the patients were similar to those of a primary care practice.

STUDY DESIGN AND VALIDITY: The authors conducted a rigorous literature search without language constraint for published and unpublished studies that were randomized or quasirandomized and double blinded comparing tolterodine with oxybutynin. At least one arm of each study needed to be randomized to 1 to 2 mg tolterodine twice daily and the other arm to 2.5 to 5 mg of oxybutynin 3 times daily. Two independent reviewers decided which trials would be considered in the analysis according to priori eligibility criteria.

OUTCOMES MEASURED: The primary outcomes included the number of incontinent episodes per 24-hour period, the quantity of pads used per 24 hours, the number of micturitions per 24 hours, and the mean voided volume per micturition. Secondary outcomes included the number of patients with side effects and withdrawals attributed to side effects, the number of patients changing dose, urologic measurements, and quality of life.

RESULTS: Oxybutynin produced a statistically and clinically significant decrease in the number of incontinent episodes per 24-hour period (weighted mean difference = 0.41; 95% confidence interval [CI], 0.04-0.77). Both drugs decreased the number of episodes, but the oxybutynin-treated group averaged 0.5 fewer episodes per day. Patients taking tolterodine reported significantly less dry mouth (relative risk [RR] = 0.54; 95% CI, 0.48-0.61) and less moderate to severe dry mouth (RR=0.33; 95% CI, 0.24-0.45). The risk of withdrawing from the study because of side effects was decreased by 37% in the tolterodine group (RR=0.63; 95% CI, 0.46-0.88).

BACKGROUND: Dexamethasone, a long-acting corticosteroid successfully used in acute treatment of croup, may prevent more relapses than prednisone in asthmatic children.

POPULATION STUDIED: The authors studied known asthmatic persons (defined by 2 or more episodes of wheezing treated with b-agonists with or without steroids) aged 2 to 18 years presenting to a children’s health hospital emergency department (ED) with an acute asthma exacerbation requiring more than 1 albuterol nebulizer treatment. Nursing staff assessed asthma severity based on either peak expired flow rates or a validated asthma severity scoring system. Children were excluded for recent oral corticosteroid treatment, history of intubation, recent varicella exposure, stridor, possible foreign body, and certain chronic diseases. During an 11-month period, 628 subjects enrolled, of whom 533 (85%) completed the study. Two thirds were men, 84% were black, and the average age was between 6 and 7 years. Fifty-six percent of the children were classified as moderate asthma severity at presentation; the remainder was evenly distributed between mild and severe.

STUDY DESIGN AND VALIDITY: This controlled trial assigned children to receive oral prednisone (2 mg/kg, maximum 60 mg, n= 261) on odd days and dexamethasone (0.6 mg/kg, maximum 16 mg, n=272) on even days. The first dose was given in the ED; the prednisone group was sent home with a prescription for 4 daily doses, the dexamethasone group was given a prepackaged dose for the following day. Children who vomited 2 doses of steroid or were directly admitted to the hospital from the ED were dropped from the study.This was a quasirandomized study, in that children were placed on one drug on even days and the other steroid on odd days. As a result, the allocation to the specific treatment groups was not concealed. Although patient severity is unlikely to have varied systematically on even and odd days, a large potential exists for a bias to be introduced into this study. Nurses who believed one treatment was superior to another could have systematically altered enrollment of children into the study based on the treatment of that day. These 2 issues—lack of randomization and concealed allocation—could invalidate the results of the study. The majority of subjects were black. Asthma prevalence, morbidity, and mortality are higher among black children, especially those in urban settings.¹ There is also some evidence of physiologic predisposition in this population, namely, higher serum immunoglobulin E levels and increased airway responsiveness.² However, no literature suggests that there is a difference in asthma treatment response between black children and children of other races or ethnicities.

OUTCOMES MEASURED: The primary outcome was rate of relapse within 10 days of discharge from the ED. Secondary outcomes were rate of hospitalization, frequency of vomiting, medication compliance, persistence of symptoms, and work or school days missed.

RESULTS: By evaluating the children who completed the study, the authors determined that the relapse rates were similar between the 2 groups, 7.4% in the dexamethasone group and 6.9% in the prednisone group (P = NS). Intention-to-treat analysis also found no difference between treatments. The number of admissions after relapse and the prevalence of persistent symptoms was also similar between the 2 groups. More children in the prednisone group missed 2 or more school days (P =.05), and more parents in this group reported not giving the medication at home (P =.004).

BACKGROUND: Dexamethasone, a long-acting corticosteroid successfully used in acute treatment of croup, may prevent more relapses than prednisone in asthmatic children.

POPULATION STUDIED: The authors studied known asthmatic persons (defined by 2 or more episodes of wheezing treated with b-agonists with or without steroids) aged 2 to 18 years presenting to a children’s health hospital emergency department (ED) with an acute asthma exacerbation requiring more than 1 albuterol nebulizer treatment. Nursing staff assessed asthma severity based on either peak expired flow rates or a validated asthma severity scoring system. Children were excluded for recent oral corticosteroid treatment, history of intubation, recent varicella exposure, stridor, possible foreign body, and certain chronic diseases. During an 11-month period, 628 subjects enrolled, of whom 533 (85%) completed the study. Two thirds were men, 84% were black, and the average age was between 6 and 7 years. Fifty-six percent of the children were classified as moderate asthma severity at presentation; the remainder was evenly distributed between mild and severe.

STUDY DESIGN AND VALIDITY: This controlled trial assigned children to receive oral prednisone (2 mg/kg, maximum 60 mg, n= 261) on odd days and dexamethasone (0.6 mg/kg, maximum 16 mg, n=272) on even days. The first dose was given in the ED; the prednisone group was sent home with a prescription for 4 daily doses, the dexamethasone group was given a prepackaged dose for the following day. Children who vomited 2 doses of steroid or were directly admitted to the hospital from the ED were dropped from the study.This was a quasirandomized study, in that children were placed on one drug on even days and the other steroid on odd days. As a result, the allocation to the specific treatment groups was not concealed. Although patient severity is unlikely to have varied systematically on even and odd days, a large potential exists for a bias to be introduced into this study. Nurses who believed one treatment was superior to another could have systematically altered enrollment of children into the study based on the treatment of that day. These 2 issues—lack of randomization and concealed allocation—could invalidate the results of the study. The majority of subjects were black. Asthma prevalence, morbidity, and mortality are higher among black children, especially those in urban settings.¹ There is also some evidence of physiologic predisposition in this population, namely, higher serum immunoglobulin E levels and increased airway responsiveness.² However, no literature suggests that there is a difference in asthma treatment response between black children and children of other races or ethnicities.

OUTCOMES MEASURED: The primary outcome was rate of relapse within 10 days of discharge from the ED. Secondary outcomes were rate of hospitalization, frequency of vomiting, medication compliance, persistence of symptoms, and work or school days missed.

RESULTS: By evaluating the children who completed the study, the authors determined that the relapse rates were similar between the 2 groups, 7.4% in the dexamethasone group and 6.9% in the prednisone group (P = NS). Intention-to-treat analysis also found no difference between treatments. The number of admissions after relapse and the prevalence of persistent symptoms was also similar between the 2 groups. More children in the prednisone group missed 2 or more school days (P =.05), and more parents in this group reported not giving the medication at home (P =.004).

BACKGROUND: Dexamethasone, a long-acting corticosteroid successfully used in acute treatment of croup, may prevent more relapses than prednisone in asthmatic children.

POPULATION STUDIED: The authors studied known asthmatic persons (defined by 2 or more episodes of wheezing treated with b-agonists with or without steroids) aged 2 to 18 years presenting to a children’s health hospital emergency department (ED) with an acute asthma exacerbation requiring more than 1 albuterol nebulizer treatment. Nursing staff assessed asthma severity based on either peak expired flow rates or a validated asthma severity scoring system. Children were excluded for recent oral corticosteroid treatment, history of intubation, recent varicella exposure, stridor, possible foreign body, and certain chronic diseases. During an 11-month period, 628 subjects enrolled, of whom 533 (85%) completed the study. Two thirds were men, 84% were black, and the average age was between 6 and 7 years. Fifty-six percent of the children were classified as moderate asthma severity at presentation; the remainder was evenly distributed between mild and severe.

STUDY DESIGN AND VALIDITY: This controlled trial assigned children to receive oral prednisone (2 mg/kg, maximum 60 mg, n= 261) on odd days and dexamethasone (0.6 mg/kg, maximum 16 mg, n=272) on even days. The first dose was given in the ED; the prednisone group was sent home with a prescription for 4 daily doses, the dexamethasone group was given a prepackaged dose for the following day. Children who vomited 2 doses of steroid or were directly admitted to the hospital from the ED were dropped from the study.This was a quasirandomized study, in that children were placed on one drug on even days and the other steroid on odd days. As a result, the allocation to the specific treatment groups was not concealed. Although patient severity is unlikely to have varied systematically on even and odd days, a large potential exists for a bias to be introduced into this study. Nurses who believed one treatment was superior to another could have systematically altered enrollment of children into the study based on the treatment of that day. These 2 issues—lack of randomization and concealed allocation—could invalidate the results of the study. The majority of subjects were black. Asthma prevalence, morbidity, and mortality are higher among black children, especially those in urban settings.¹ There is also some evidence of physiologic predisposition in this population, namely, higher serum immunoglobulin E levels and increased airway responsiveness.² However, no literature suggests that there is a difference in asthma treatment response between black children and children of other races or ethnicities.

OUTCOMES MEASURED: The primary outcome was rate of relapse within 10 days of discharge from the ED. Secondary outcomes were rate of hospitalization, frequency of vomiting, medication compliance, persistence of symptoms, and work or school days missed.

RESULTS: By evaluating the children who completed the study, the authors determined that the relapse rates were similar between the 2 groups, 7.4% in the dexamethasone group and 6.9% in the prednisone group (P = NS). Intention-to-treat analysis also found no difference between treatments. The number of admissions after relapse and the prevalence of persistent symptoms was also similar between the 2 groups. More children in the prednisone group missed 2 or more school days (P =.05), and more parents in this group reported not giving the medication at home (P =.004).