Q&A

ABSTRACT

BACKGROUND: Significant morbidity and mortality may result after influenza infection in the elderly. Influenza vaccination is recommended for all persons older than 65 years but does not confer universal protection against disease or complications. Chemoprophylaxis against influenza with oseltamivir is effective in a younger unvaccinated population but has not been studied in an elderly vaccinated population.

POPULATION STUDIED: The study population included residents of long-term care facilities located throughout the United States and Europe. Of the 548 subjects enrolled (272 placebo, 276 oseltamivir), 493 completed the study. Study groups were similar at baseline. Residents 65 years and older were included; the mean age was approximately 81 years. Participants had a mean of 6.1 concurrent diseases and were taking an average of 7.7 medications. Approximately 80% of participants received the influenza vaccination.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind placebo-controlled study. Participants were recruited during the 1998-1999 influenza season and performed a stratified randomization according to vaccination status and coexistence of chronic obstructive airways disease. Subjects took either oseltamivir 75 mg or placebo once daily for 6 weeks. Treatment was started when influenza infection was detected in either one resident of the center or in two individuals in the immediate community. Participants were examined at 3, 6, and 8 weeks and when influenza-like symptoms were documented on daily diary cards.

OUTCOMES MEASURED: The primary outcome was incidence of laboratory-confirmed clinical influenza A or B, defined as fever, one respiratory symptom, and one constitutional symptom plus a greater than 4-fold increase in influenza antibody titer or viral replication from nasal or throat swabs. Secondary outcomes included symptomatic laboratory-confirmed influenza not meeting clinical criteria, asymptomatic laboratory-confirmed influenza, influenza-like illness, and secondary influenza complications (otitis media, sinusitis, bronchitis, or pneumonia).

RESULTS: Thirteen cases of laboratory-confirmed clinical influenza were identified; 12 of the 13 infected patients previously had been vaccinated. No influenza occurred in 22 of the 31 participating study sites. Compared with placebo, treatment with oseltamivir significantly protected against laboratory-confirmed influenza (4.4% vs. 0.4%; P=.002; number needed to treat [NNT]=25) and reduced secondary influenza complications (2.6% vs 0.4%; P=.037; NNT=45). The difference in rates of pneumonia (1.1% vs 0.0%) is not clinically significant. Adverse events were not more likely in oseltamivir-treated patients and withdrawals due to adverse events was similar among the patients in the 2 groups. One patient died in each study group (unrelated to influenza or study medication).

ABSTRACT

BACKGROUND: Significant morbidity and mortality may result after influenza infection in the elderly. Influenza vaccination is recommended for all persons older than 65 years but does not confer universal protection against disease or complications. Chemoprophylaxis against influenza with oseltamivir is effective in a younger unvaccinated population but has not been studied in an elderly vaccinated population.

POPULATION STUDIED: The study population included residents of long-term care facilities located throughout the United States and Europe. Of the 548 subjects enrolled (272 placebo, 276 oseltamivir), 493 completed the study. Study groups were similar at baseline. Residents 65 years and older were included; the mean age was approximately 81 years. Participants had a mean of 6.1 concurrent diseases and were taking an average of 7.7 medications. Approximately 80% of participants received the influenza vaccination.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind placebo-controlled study. Participants were recruited during the 1998-1999 influenza season and performed a stratified randomization according to vaccination status and coexistence of chronic obstructive airways disease. Subjects took either oseltamivir 75 mg or placebo once daily for 6 weeks. Treatment was started when influenza infection was detected in either one resident of the center or in two individuals in the immediate community. Participants were examined at 3, 6, and 8 weeks and when influenza-like symptoms were documented on daily diary cards.

OUTCOMES MEASURED: The primary outcome was incidence of laboratory-confirmed clinical influenza A or B, defined as fever, one respiratory symptom, and one constitutional symptom plus a greater than 4-fold increase in influenza antibody titer or viral replication from nasal or throat swabs. Secondary outcomes included symptomatic laboratory-confirmed influenza not meeting clinical criteria, asymptomatic laboratory-confirmed influenza, influenza-like illness, and secondary influenza complications (otitis media, sinusitis, bronchitis, or pneumonia).

RESULTS: Thirteen cases of laboratory-confirmed clinical influenza were identified; 12 of the 13 infected patients previously had been vaccinated. No influenza occurred in 22 of the 31 participating study sites. Compared with placebo, treatment with oseltamivir significantly protected against laboratory-confirmed influenza (4.4% vs. 0.4%; P=.002; number needed to treat [NNT]=25) and reduced secondary influenza complications (2.6% vs 0.4%; P=.037; NNT=45). The difference in rates of pneumonia (1.1% vs 0.0%) is not clinically significant. Adverse events were not more likely in oseltamivir-treated patients and withdrawals due to adverse events was similar among the patients in the 2 groups. One patient died in each study group (unrelated to influenza or study medication).

ABSTRACT

BACKGROUND: Significant morbidity and mortality may result after influenza infection in the elderly. Influenza vaccination is recommended for all persons older than 65 years but does not confer universal protection against disease or complications. Chemoprophylaxis against influenza with oseltamivir is effective in a younger unvaccinated population but has not been studied in an elderly vaccinated population.

POPULATION STUDIED: The study population included residents of long-term care facilities located throughout the United States and Europe. Of the 548 subjects enrolled (272 placebo, 276 oseltamivir), 493 completed the study. Study groups were similar at baseline. Residents 65 years and older were included; the mean age was approximately 81 years. Participants had a mean of 6.1 concurrent diseases and were taking an average of 7.7 medications. Approximately 80% of participants received the influenza vaccination.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind placebo-controlled study. Participants were recruited during the 1998-1999 influenza season and performed a stratified randomization according to vaccination status and coexistence of chronic obstructive airways disease. Subjects took either oseltamivir 75 mg or placebo once daily for 6 weeks. Treatment was started when influenza infection was detected in either one resident of the center or in two individuals in the immediate community. Participants were examined at 3, 6, and 8 weeks and when influenza-like symptoms were documented on daily diary cards.

OUTCOMES MEASURED: The primary outcome was incidence of laboratory-confirmed clinical influenza A or B, defined as fever, one respiratory symptom, and one constitutional symptom plus a greater than 4-fold increase in influenza antibody titer or viral replication from nasal or throat swabs. Secondary outcomes included symptomatic laboratory-confirmed influenza not meeting clinical criteria, asymptomatic laboratory-confirmed influenza, influenza-like illness, and secondary influenza complications (otitis media, sinusitis, bronchitis, or pneumonia).

RESULTS: Thirteen cases of laboratory-confirmed clinical influenza were identified; 12 of the 13 infected patients previously had been vaccinated. No influenza occurred in 22 of the 31 participating study sites. Compared with placebo, treatment with oseltamivir significantly protected against laboratory-confirmed influenza (4.4% vs. 0.4%; P=.002; number needed to treat [NNT]=25) and reduced secondary influenza complications (2.6% vs 0.4%; P=.037; NNT=45). The difference in rates of pneumonia (1.1% vs 0.0%) is not clinically significant. Adverse events were not more likely in oseltamivir-treated patients and withdrawals due to adverse events was similar among the patients in the 2 groups. One patient died in each study group (unrelated to influenza or study medication).

ABSTRACT

BACKGROUND: Some women with acne may suffer from a hypersensitivity of the sebaceous glands to androgens. The use of OCPs with anti-androgenic properties may therefore be a useful approach to treating these patients.

POPULATION STUDIED: The population studied included 199 women 18 to 40 years of age (smokers up to age 30 years), with mild to moderate papulo pustular acne of the face and acne-related disorders. Patients were recruited from 32 office-based gynecology centers in Germany.

STUDY DESIGN AND VALIDITY: Patients were randomized in an investigator blinded-only fashion (nonconcealed allocation assignment) to 12 treatment cycles with one of 2 OCPs—either Belara, a monophasic OCP containing 0.3 mg of ethinylestradiol and 2 mg of chlormadinone acetate (EE/CMA), a progestogen derivative with anti-androgenic properties or Microgynon, an OCP containing an equal dose of estrogen and a more commonly used progestin, levonorgestrel (EE/LNG). Blinded observers performed regular skin exams after cycles 4, 7, 10 and 12. Women were not allowed to use any other treatments for acne.

OUTCOMES MEASURED: The primary endpoint was the number of papules/pustules per half of the face decreasing by 50% in the 12th medication cycle. Secondary endpoints were the assessment of comedomal acne of the face, acne of the décolleté and back, further signs of adrogenization, such as seborrhea, alopecia, and hirsuitism. Blood levels of androgens, SHBG, cycle stability and incidence of adverse events were also examined.

RESULTS: A total of 59% of patients on EE/CMA compared with 46% on EE/LNG showed a 50% reduction in the number of papules/pustules after 12 treatment cycles (P=.02; number needed to treat=8). The number of women with complete resolution reached 16.5% by cycle 12 in those taking EE/CMA compared with 4.3% by cycle 12 in the EE/LNG group (difference nonsignificant). Similar nonsignificant trends were seen for a reduction in comedonal acne favoring the EE/CMA group. Equal improvements were seen in each group for seborrhea, alopecia, and hirsuitism. There was no difference in the incidence and intensity of break-through bleeding or amenorrhea between the 2 groups. Adverse events were similar between the 2 groups.

ABSTRACT

BACKGROUND: Some women with acne may suffer from a hypersensitivity of the sebaceous glands to androgens. The use of OCPs with anti-androgenic properties may therefore be a useful approach to treating these patients.

POPULATION STUDIED: The population studied included 199 women 18 to 40 years of age (smokers up to age 30 years), with mild to moderate papulo pustular acne of the face and acne-related disorders. Patients were recruited from 32 office-based gynecology centers in Germany.

STUDY DESIGN AND VALIDITY: Patients were randomized in an investigator blinded-only fashion (nonconcealed allocation assignment) to 12 treatment cycles with one of 2 OCPs—either Belara, a monophasic OCP containing 0.3 mg of ethinylestradiol and 2 mg of chlormadinone acetate (EE/CMA), a progestogen derivative with anti-androgenic properties or Microgynon, an OCP containing an equal dose of estrogen and a more commonly used progestin, levonorgestrel (EE/LNG). Blinded observers performed regular skin exams after cycles 4, 7, 10 and 12. Women were not allowed to use any other treatments for acne.

OUTCOMES MEASURED: The primary endpoint was the number of papules/pustules per half of the face decreasing by 50% in the 12th medication cycle. Secondary endpoints were the assessment of comedomal acne of the face, acne of the décolleté and back, further signs of adrogenization, such as seborrhea, alopecia, and hirsuitism. Blood levels of androgens, SHBG, cycle stability and incidence of adverse events were also examined.

RESULTS: A total of 59% of patients on EE/CMA compared with 46% on EE/LNG showed a 50% reduction in the number of papules/pustules after 12 treatment cycles (P=.02; number needed to treat=8). The number of women with complete resolution reached 16.5% by cycle 12 in those taking EE/CMA compared with 4.3% by cycle 12 in the EE/LNG group (difference nonsignificant). Similar nonsignificant trends were seen for a reduction in comedonal acne favoring the EE/CMA group. Equal improvements were seen in each group for seborrhea, alopecia, and hirsuitism. There was no difference in the incidence and intensity of break-through bleeding or amenorrhea between the 2 groups. Adverse events were similar between the 2 groups.

ABSTRACT

BACKGROUND: Some women with acne may suffer from a hypersensitivity of the sebaceous glands to androgens. The use of OCPs with anti-androgenic properties may therefore be a useful approach to treating these patients.

POPULATION STUDIED: The population studied included 199 women 18 to 40 years of age (smokers up to age 30 years), with mild to moderate papulo pustular acne of the face and acne-related disorders. Patients were recruited from 32 office-based gynecology centers in Germany.

STUDY DESIGN AND VALIDITY: Patients were randomized in an investigator blinded-only fashion (nonconcealed allocation assignment) to 12 treatment cycles with one of 2 OCPs—either Belara, a monophasic OCP containing 0.3 mg of ethinylestradiol and 2 mg of chlormadinone acetate (EE/CMA), a progestogen derivative with anti-androgenic properties or Microgynon, an OCP containing an equal dose of estrogen and a more commonly used progestin, levonorgestrel (EE/LNG). Blinded observers performed regular skin exams after cycles 4, 7, 10 and 12. Women were not allowed to use any other treatments for acne.

OUTCOMES MEASURED: The primary endpoint was the number of papules/pustules per half of the face decreasing by 50% in the 12th medication cycle. Secondary endpoints were the assessment of comedomal acne of the face, acne of the décolleté and back, further signs of adrogenization, such as seborrhea, alopecia, and hirsuitism. Blood levels of androgens, SHBG, cycle stability and incidence of adverse events were also examined.

RESULTS: A total of 59% of patients on EE/CMA compared with 46% on EE/LNG showed a 50% reduction in the number of papules/pustules after 12 treatment cycles (P=.02; number needed to treat=8). The number of women with complete resolution reached 16.5% by cycle 12 in those taking EE/CMA compared with 4.3% by cycle 12 in the EE/LNG group (difference nonsignificant). Similar nonsignificant trends were seen for a reduction in comedonal acne favoring the EE/CMA group. Equal improvements were seen in each group for seborrhea, alopecia, and hirsuitism. There was no difference in the incidence and intensity of break-through bleeding or amenorrhea between the 2 groups. Adverse events were similar between the 2 groups.

ABSTRACT

BACKGROUND: An accurate physical examination of knee pain can aid in determining the need for further diagnostic testing, specialist referral, and surgical intervention.

POPULATION STUDIED: The authors of this systematic review conducted searches of MEDLINE, Health STAR, and bibliographies of retrieved articles. They identified 88 articles of which 23 compared physical examination techniques to a reference standard (arthroscopy, arthrotomy, or magnetic resonance imaging).

STUDY DESIGN AND VALIDITY: Two of the authors graded the methodologic quality of the included studies using a standardized scoring system. The authors abstracted data from individual studies to calculate the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for specific examination techniques.

OUTCOMES MEASURED: The sensitivity, specificity, LR+, and LR- were calculated for examination of anterior cruciate ligament (ACL) injuries (“composite” examination and Lachman, anterior drawer, and lateral pivot shift maneuvers), posterior cruciate ligament (PCL) injuries (“general” examination and posterior drawer and abduction stress test maneuvers), and for meniscus injuries (joint line tenderness, presence of joint effusion, and the McMurray and medial-lateral grind tests). No articles were found that examined the diagnostic accuracy of physical examination techniques for medial collateral ligament (MCL) or lateral collateral ligament (LCL) injuries. The review includes detailed descriptions of the examination techniques.

RESULTS: The results for all of the diagnostic tests are in the form of LRs. An LR greater than 10 provides strong evidence that the disorder is present; an LR less than 0.1 provides strong evidence that the disorder is not present. Scores between 0.5 and 2.0 are neutral. Summary LRs with 95% confidence intervals (95% CI) for examinations of ACL injuries were as follows: composite examination (specific maneuvers not delineated): LR+ = 25.0 (95% CI, 2.1-306.2), LR- = 0.04 (95% CI, 0.01-0.48); the Lachman test: LR+ = 25.0 (95% CI, 2.7 -651), LR - = 0.1 (95% CI, 0.0 - 0.4); anterior drawer test: LR+ = 3.8 (95% CI, 0.7 - 22.0), LR- = 0.3 (95% CI, 0.05 -1.50); and pivot shift stress test: LR+ = 42 (95% CI, 2.7-651.0) and LR- = 0.1 (95% CI, 0.0-0.4).

ABSTRACT

BACKGROUND: An accurate physical examination of knee pain can aid in determining the need for further diagnostic testing, specialist referral, and surgical intervention.

POPULATION STUDIED: The authors of this systematic review conducted searches of MEDLINE, Health STAR, and bibliographies of retrieved articles. They identified 88 articles of which 23 compared physical examination techniques to a reference standard (arthroscopy, arthrotomy, or magnetic resonance imaging).

STUDY DESIGN AND VALIDITY: Two of the authors graded the methodologic quality of the included studies using a standardized scoring system. The authors abstracted data from individual studies to calculate the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for specific examination techniques.

OUTCOMES MEASURED: The sensitivity, specificity, LR+, and LR- were calculated for examination of anterior cruciate ligament (ACL) injuries (“composite” examination and Lachman, anterior drawer, and lateral pivot shift maneuvers), posterior cruciate ligament (PCL) injuries (“general” examination and posterior drawer and abduction stress test maneuvers), and for meniscus injuries (joint line tenderness, presence of joint effusion, and the McMurray and medial-lateral grind tests). No articles were found that examined the diagnostic accuracy of physical examination techniques for medial collateral ligament (MCL) or lateral collateral ligament (LCL) injuries. The review includes detailed descriptions of the examination techniques.

RESULTS: The results for all of the diagnostic tests are in the form of LRs. An LR greater than 10 provides strong evidence that the disorder is present; an LR less than 0.1 provides strong evidence that the disorder is not present. Scores between 0.5 and 2.0 are neutral. Summary LRs with 95% confidence intervals (95% CI) for examinations of ACL injuries were as follows: composite examination (specific maneuvers not delineated): LR+ = 25.0 (95% CI, 2.1-306.2), LR- = 0.04 (95% CI, 0.01-0.48); the Lachman test: LR+ = 25.0 (95% CI, 2.7 -651), LR - = 0.1 (95% CI, 0.0 - 0.4); anterior drawer test: LR+ = 3.8 (95% CI, 0.7 - 22.0), LR- = 0.3 (95% CI, 0.05 -1.50); and pivot shift stress test: LR+ = 42 (95% CI, 2.7-651.0) and LR- = 0.1 (95% CI, 0.0-0.4).

ABSTRACT

BACKGROUND: An accurate physical examination of knee pain can aid in determining the need for further diagnostic testing, specialist referral, and surgical intervention.

POPULATION STUDIED: The authors of this systematic review conducted searches of MEDLINE, Health STAR, and bibliographies of retrieved articles. They identified 88 articles of which 23 compared physical examination techniques to a reference standard (arthroscopy, arthrotomy, or magnetic resonance imaging).

STUDY DESIGN AND VALIDITY: Two of the authors graded the methodologic quality of the included studies using a standardized scoring system. The authors abstracted data from individual studies to calculate the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for specific examination techniques.

OUTCOMES MEASURED: The sensitivity, specificity, LR+, and LR- were calculated for examination of anterior cruciate ligament (ACL) injuries (“composite” examination and Lachman, anterior drawer, and lateral pivot shift maneuvers), posterior cruciate ligament (PCL) injuries (“general” examination and posterior drawer and abduction stress test maneuvers), and for meniscus injuries (joint line tenderness, presence of joint effusion, and the McMurray and medial-lateral grind tests). No articles were found that examined the diagnostic accuracy of physical examination techniques for medial collateral ligament (MCL) or lateral collateral ligament (LCL) injuries. The review includes detailed descriptions of the examination techniques.

RESULTS: The results for all of the diagnostic tests are in the form of LRs. An LR greater than 10 provides strong evidence that the disorder is present; an LR less than 0.1 provides strong evidence that the disorder is not present. Scores between 0.5 and 2.0 are neutral. Summary LRs with 95% confidence intervals (95% CI) for examinations of ACL injuries were as follows: composite examination (specific maneuvers not delineated): LR+ = 25.0 (95% CI, 2.1-306.2), LR- = 0.04 (95% CI, 0.01-0.48); the Lachman test: LR+ = 25.0 (95% CI, 2.7 -651), LR - = 0.1 (95% CI, 0.0 - 0.4); anterior drawer test: LR+ = 3.8 (95% CI, 0.7 - 22.0), LR- = 0.3 (95% CI, 0.05 -1.50); and pivot shift stress test: LR+ = 42 (95% CI, 2.7-651.0) and LR- = 0.1 (95% CI, 0.0-0.4).

ABSTRACT

BACKGROUND: The standard treatment for iron deficiency anemia in preschool children has been 4.5 to 6.0 mg per kg per day of ferrous sulfate divided into 3 daily doses. Given the difficulty of giving medicine 3 times per day to young children, less frequent dosing should improve compliance.

POPULATION STUDIED: Infants aged between 6 and 18 months with a hemoglobin concentration between 7.0 and 9.9 g per dL were enrolled in the study. The study was conducted in Ghana, a malaria-endemic area, with an 83% prevalence of anemia in young children (compared with a 3%-5% prevalence in the United States).

STUDY DESIGN AND VALIDITY: The investigators of this randomized controlled trial screened 880 infants to find 557 who were eligible. These children were divided by concealed allocation to standard dose (5 mg per kg per day of elemental iron, rounded to a total of 40 mg of elemental iron given in 3 equal daily doses) or single-dose (40 mg of elemental iron as a single bolus dose) ferrous sulfate drops. Children had blood samples analyzed for hemoglobin concentration and serum ferritin at entry and after 2 months of therapy. Also, a peripheral blood smear was obtained at entry to look for malaria parasites.

OUTCOMES MEASURED: The primary outcome was percentage of children whose anemia resolved (hemoglobin concentration > 10.0 g/dL). Ferritin levels, compliance, and side effects were also measured and reported.

RESULTS: Anemia resolved in 59% of the infants after 2 months of therapy. There was no significant difference in the response rate between the once-daily group and the thrice-daily group (61% vs 56%; P=.51). Final mean hemoglobin (10.2 g/dL vs 10.0 g/dL; P=.25) and ferritin (101 μg/L vs 107 μg/L; P=0.1) values (in the once-daily and thrice-daily groups respectively) were all significantly increased from baseline but not significantly different between groups.

ABSTRACT

BACKGROUND: The standard treatment for iron deficiency anemia in preschool children has been 4.5 to 6.0 mg per kg per day of ferrous sulfate divided into 3 daily doses. Given the difficulty of giving medicine 3 times per day to young children, less frequent dosing should improve compliance.

POPULATION STUDIED: Infants aged between 6 and 18 months with a hemoglobin concentration between 7.0 and 9.9 g per dL were enrolled in the study. The study was conducted in Ghana, a malaria-endemic area, with an 83% prevalence of anemia in young children (compared with a 3%-5% prevalence in the United States).

STUDY DESIGN AND VALIDITY: The investigators of this randomized controlled trial screened 880 infants to find 557 who were eligible. These children were divided by concealed allocation to standard dose (5 mg per kg per day of elemental iron, rounded to a total of 40 mg of elemental iron given in 3 equal daily doses) or single-dose (40 mg of elemental iron as a single bolus dose) ferrous sulfate drops. Children had blood samples analyzed for hemoglobin concentration and serum ferritin at entry and after 2 months of therapy. Also, a peripheral blood smear was obtained at entry to look for malaria parasites.

OUTCOMES MEASURED: The primary outcome was percentage of children whose anemia resolved (hemoglobin concentration > 10.0 g/dL). Ferritin levels, compliance, and side effects were also measured and reported.

RESULTS: Anemia resolved in 59% of the infants after 2 months of therapy. There was no significant difference in the response rate between the once-daily group and the thrice-daily group (61% vs 56%; P=.51). Final mean hemoglobin (10.2 g/dL vs 10.0 g/dL; P=.25) and ferritin (101 μg/L vs 107 μg/L; P=0.1) values (in the once-daily and thrice-daily groups respectively) were all significantly increased from baseline but not significantly different between groups.

ABSTRACT

BACKGROUND: The standard treatment for iron deficiency anemia in preschool children has been 4.5 to 6.0 mg per kg per day of ferrous sulfate divided into 3 daily doses. Given the difficulty of giving medicine 3 times per day to young children, less frequent dosing should improve compliance.

POPULATION STUDIED: Infants aged between 6 and 18 months with a hemoglobin concentration between 7.0 and 9.9 g per dL were enrolled in the study. The study was conducted in Ghana, a malaria-endemic area, with an 83% prevalence of anemia in young children (compared with a 3%-5% prevalence in the United States).

STUDY DESIGN AND VALIDITY: The investigators of this randomized controlled trial screened 880 infants to find 557 who were eligible. These children were divided by concealed allocation to standard dose (5 mg per kg per day of elemental iron, rounded to a total of 40 mg of elemental iron given in 3 equal daily doses) or single-dose (40 mg of elemental iron as a single bolus dose) ferrous sulfate drops. Children had blood samples analyzed for hemoglobin concentration and serum ferritin at entry and after 2 months of therapy. Also, a peripheral blood smear was obtained at entry to look for malaria parasites.

OUTCOMES MEASURED: The primary outcome was percentage of children whose anemia resolved (hemoglobin concentration > 10.0 g/dL). Ferritin levels, compliance, and side effects were also measured and reported.

RESULTS: Anemia resolved in 59% of the infants after 2 months of therapy. There was no significant difference in the response rate between the once-daily group and the thrice-daily group (61% vs 56%; P=.51). Final mean hemoglobin (10.2 g/dL vs 10.0 g/dL; P=.25) and ferritin (101 μg/L vs 107 μg/L; P=0.1) values (in the once-daily and thrice-daily groups respectively) were all significantly increased from baseline but not significantly different between groups.

ABSTRACT

BACKGROUND: Based on randomized clinical trials (RCTs), the most effective first-line eradication therapy for Helicobacter pylori is a combination of proton pump inhibitor (PPI) and 2 antimicrobial agents.¹ Yet there remains a significant treatment failure rate of 5% to 25%. Antibiotic resistance is the major impediment of cure.² Using a pooled analysis approach, the authors determined the second-line treatment strategy resulting in the greatest percentage of H pylorieradication.

POPULATION STUDIED: Studies of H pylori re-eradication in adults were retrieved from MEDLINE database, reference lists of retrieved research papers, and major congress abstract lists. All studies were performed between 1994 and 1999, were conducted prospectively (or without information on study design), contained detailed information on eradication agents, and included subjects with only one treatment failure. Eighteen articles and 47 abstracts were identified; 16 articles and 24 abstracts met the inclusion criteria.

STUDY DESIGN AND VALIDITY: The authors performed a pooled efficacy analysis of re-treatment regimens for H pylori eradication in adults. They included all prospective studies—randomized and nonrandomized—that reported eradication rates in patients previously treated with antibiotic therapy. The inclusion criteria were appropriate, and the search for relevant articles was complete in that the authors included abstracts from international gastroenterology meetings. An analysis strategy of simple pooling was used (total number of patients successfully treated divided by all those enrolled in given treatment category), which is appropriate since the primary outcome was the eradication rate.

OUTCOMES MEASURED: The authors calculated a pooled eradication rate with 95% confidence intervals for each of the 6 general treatment categories. They also determined the eradication rate of each second treatment, accounting for differences in initial treatment therapy regimen. Finally, they ascertained if the effectiveness of second-line therapy regimens improved when distinct antimicrobials not used in the first attempt at treatment were used.

RESULTS: The most effective second-line therapies for eradication of H pylori were quadruple therapy, either ranitidine-bismuth-based triple therapy (ranitidine-bismuth product plus 2 antimicrobials) at 80.2% (95% confidence interval [CI], 75%-85%) or H2-blocker or PPI, bismuth compound, and 2 antimicrobials) at 75.8% (95% CI, 73%-79%). The second-line treatment eradication rate was lower when the initial therapy was a PPI with 2 antimicrobials versus a PPI with one antimicrobial. Re-treatment was more difficult with an increased number of antimicrobials used in initial therapy. The re-treatment eradication rate was greater when 2 new antimicrobials were included in the regimen than when a single new antimicrobial was added (P=.0064).

ABSTRACT

BACKGROUND: Based on randomized clinical trials (RCTs), the most effective first-line eradication therapy for Helicobacter pylori is a combination of proton pump inhibitor (PPI) and 2 antimicrobial agents.¹ Yet there remains a significant treatment failure rate of 5% to 25%. Antibiotic resistance is the major impediment of cure.² Using a pooled analysis approach, the authors determined the second-line treatment strategy resulting in the greatest percentage of H pylorieradication.

POPULATION STUDIED: Studies of H pylori re-eradication in adults were retrieved from MEDLINE database, reference lists of retrieved research papers, and major congress abstract lists. All studies were performed between 1994 and 1999, were conducted prospectively (or without information on study design), contained detailed information on eradication agents, and included subjects with only one treatment failure. Eighteen articles and 47 abstracts were identified; 16 articles and 24 abstracts met the inclusion criteria.

STUDY DESIGN AND VALIDITY: The authors performed a pooled efficacy analysis of re-treatment regimens for H pylori eradication in adults. They included all prospective studies—randomized and nonrandomized—that reported eradication rates in patients previously treated with antibiotic therapy. The inclusion criteria were appropriate, and the search for relevant articles was complete in that the authors included abstracts from international gastroenterology meetings. An analysis strategy of simple pooling was used (total number of patients successfully treated divided by all those enrolled in given treatment category), which is appropriate since the primary outcome was the eradication rate.

OUTCOMES MEASURED: The authors calculated a pooled eradication rate with 95% confidence intervals for each of the 6 general treatment categories. They also determined the eradication rate of each second treatment, accounting for differences in initial treatment therapy regimen. Finally, they ascertained if the effectiveness of second-line therapy regimens improved when distinct antimicrobials not used in the first attempt at treatment were used.

RESULTS: The most effective second-line therapies for eradication of H pylori were quadruple therapy, either ranitidine-bismuth-based triple therapy (ranitidine-bismuth product plus 2 antimicrobials) at 80.2% (95% confidence interval [CI], 75%-85%) or H2-blocker or PPI, bismuth compound, and 2 antimicrobials) at 75.8% (95% CI, 73%-79%). The second-line treatment eradication rate was lower when the initial therapy was a PPI with 2 antimicrobials versus a PPI with one antimicrobial. Re-treatment was more difficult with an increased number of antimicrobials used in initial therapy. The re-treatment eradication rate was greater when 2 new antimicrobials were included in the regimen than when a single new antimicrobial was added (P=.0064).

ABSTRACT

BACKGROUND: Based on randomized clinical trials (RCTs), the most effective first-line eradication therapy for Helicobacter pylori is a combination of proton pump inhibitor (PPI) and 2 antimicrobial agents.¹ Yet there remains a significant treatment failure rate of 5% to 25%. Antibiotic resistance is the major impediment of cure.² Using a pooled analysis approach, the authors determined the second-line treatment strategy resulting in the greatest percentage of H pylorieradication.

POPULATION STUDIED: Studies of H pylori re-eradication in adults were retrieved from MEDLINE database, reference lists of retrieved research papers, and major congress abstract lists. All studies were performed between 1994 and 1999, were conducted prospectively (or without information on study design), contained detailed information on eradication agents, and included subjects with only one treatment failure. Eighteen articles and 47 abstracts were identified; 16 articles and 24 abstracts met the inclusion criteria.

STUDY DESIGN AND VALIDITY: The authors performed a pooled efficacy analysis of re-treatment regimens for H pylori eradication in adults. They included all prospective studies—randomized and nonrandomized—that reported eradication rates in patients previously treated with antibiotic therapy. The inclusion criteria were appropriate, and the search for relevant articles was complete in that the authors included abstracts from international gastroenterology meetings. An analysis strategy of simple pooling was used (total number of patients successfully treated divided by all those enrolled in given treatment category), which is appropriate since the primary outcome was the eradication rate.

OUTCOMES MEASURED: The authors calculated a pooled eradication rate with 95% confidence intervals for each of the 6 general treatment categories. They also determined the eradication rate of each second treatment, accounting for differences in initial treatment therapy regimen. Finally, they ascertained if the effectiveness of second-line therapy regimens improved when distinct antimicrobials not used in the first attempt at treatment were used.

RESULTS: The most effective second-line therapies for eradication of H pylori were quadruple therapy, either ranitidine-bismuth-based triple therapy (ranitidine-bismuth product plus 2 antimicrobials) at 80.2% (95% confidence interval [CI], 75%-85%) or H2-blocker or PPI, bismuth compound, and 2 antimicrobials) at 75.8% (95% CI, 73%-79%). The second-line treatment eradication rate was lower when the initial therapy was a PPI with 2 antimicrobials versus a PPI with one antimicrobial. Re-treatment was more difficult with an increased number of antimicrobials used in initial therapy. The re-treatment eradication rate was greater when 2 new antimicrobials were included in the regimen than when a single new antimicrobial was added (P=.0064).

ABSTRACT

BACKGROUND: For women at high risk of preterm delivery, it is the standard of care to administer an initial course of corticosteroids to promote lung maturity. Uncertainty remains, however, about the value of continuing treatments on a regular (weekly) schedule. This randomized controlled trial compared the efficacy of single versus weekly corticosteroids in reducing neonatal morbidity in women at high risk of preterm delivery.

POPULATION STUDIED: A total of 502 women between 24 weeks’ and 32 weeks and 6 days’ gestation at high risk for preterm delivery were recruited from 13 US academic centers. High risk was defined as preterm labor, preterm rupture of membranes, maternal medical illness, or suspected intrauterine growth restriction. Women were excluded if they needed immediate delivery, had active tuberculosis or human immunodeficiency virus infection, or if their fetuses had mature lungs or severe anomalies. Approximately equal proportions of subjects were white, Hispanic, and African American, and 67% were receiving government assistance. Also, 33% were nulliparous; 54% had preterm labor; and 14.5% had multiple gestations.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded trial. Women at high risk for preterm delivery who received an initial course of corticosteroids and had not delivered in 1 week were randomized to receive either betamethasone 12 mg twice in 24 hours every week until 34 weeks or similarly administered placebo. Analysis was by intention to treat, using chi-square tests and t tests with assessment of study site as a potential confounder. The study was halted after 502 of a planned 1000 patients were recruited, due to emerging evidence that weekly corticosteroids might produce long-term neurologic sequelae. The methodology of this study was strong. The major weakness was lack of statistical power.

OUTCOMES MEASURED: The primary outcome was composite neonatal morbidity (including severe RDS, BPD and IVH, periventricular leukomalacia, sepsis, NEC, or death). Secondary outcomes included each individual outcome, maternal side effects, and clinical course. Utilization, cost, and patient satisfaction were not addressed.

RESULTS: The groups were similar at baseline and follow up was 97%. There was no significant difference in composite morbidity between the weekly course group and the single-course group. Exploratory analysis showed that weekly corticosteroids decreased severe RDS (15.3% vs 24.1%; P=.01), but there also a trend toward an increased risk of severe IVH in the weekly course group (7.6% vs 2.0%; P=.06). The weekly course group had shorter time to delivery (5.0 vs 5.8 weeks; P=.02) and a trend towards more chorioamnionitis (24.1% vs 17.8%; P=.09). There was no significant difference between the 2 treatment regimens in endometritis, wound infections, hemorrhage, or length of stay.

ABSTRACT

BACKGROUND: For women at high risk of preterm delivery, it is the standard of care to administer an initial course of corticosteroids to promote lung maturity. Uncertainty remains, however, about the value of continuing treatments on a regular (weekly) schedule. This randomized controlled trial compared the efficacy of single versus weekly corticosteroids in reducing neonatal morbidity in women at high risk of preterm delivery.

POPULATION STUDIED: A total of 502 women between 24 weeks’ and 32 weeks and 6 days’ gestation at high risk for preterm delivery were recruited from 13 US academic centers. High risk was defined as preterm labor, preterm rupture of membranes, maternal medical illness, or suspected intrauterine growth restriction. Women were excluded if they needed immediate delivery, had active tuberculosis or human immunodeficiency virus infection, or if their fetuses had mature lungs or severe anomalies. Approximately equal proportions of subjects were white, Hispanic, and African American, and 67% were receiving government assistance. Also, 33% were nulliparous; 54% had preterm labor; and 14.5% had multiple gestations.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded trial. Women at high risk for preterm delivery who received an initial course of corticosteroids and had not delivered in 1 week were randomized to receive either betamethasone 12 mg twice in 24 hours every week until 34 weeks or similarly administered placebo. Analysis was by intention to treat, using chi-square tests and t tests with assessment of study site as a potential confounder. The study was halted after 502 of a planned 1000 patients were recruited, due to emerging evidence that weekly corticosteroids might produce long-term neurologic sequelae. The methodology of this study was strong. The major weakness was lack of statistical power.

OUTCOMES MEASURED: The primary outcome was composite neonatal morbidity (including severe RDS, BPD and IVH, periventricular leukomalacia, sepsis, NEC, or death). Secondary outcomes included each individual outcome, maternal side effects, and clinical course. Utilization, cost, and patient satisfaction were not addressed.

RESULTS: The groups were similar at baseline and follow up was 97%. There was no significant difference in composite morbidity between the weekly course group and the single-course group. Exploratory analysis showed that weekly corticosteroids decreased severe RDS (15.3% vs 24.1%; P=.01), but there also a trend toward an increased risk of severe IVH in the weekly course group (7.6% vs 2.0%; P=.06). The weekly course group had shorter time to delivery (5.0 vs 5.8 weeks; P=.02) and a trend towards more chorioamnionitis (24.1% vs 17.8%; P=.09). There was no significant difference between the 2 treatment regimens in endometritis, wound infections, hemorrhage, or length of stay.

ABSTRACT

BACKGROUND: For women at high risk of preterm delivery, it is the standard of care to administer an initial course of corticosteroids to promote lung maturity. Uncertainty remains, however, about the value of continuing treatments on a regular (weekly) schedule. This randomized controlled trial compared the efficacy of single versus weekly corticosteroids in reducing neonatal morbidity in women at high risk of preterm delivery.

POPULATION STUDIED: A total of 502 women between 24 weeks’ and 32 weeks and 6 days’ gestation at high risk for preterm delivery were recruited from 13 US academic centers. High risk was defined as preterm labor, preterm rupture of membranes, maternal medical illness, or suspected intrauterine growth restriction. Women were excluded if they needed immediate delivery, had active tuberculosis or human immunodeficiency virus infection, or if their fetuses had mature lungs or severe anomalies. Approximately equal proportions of subjects were white, Hispanic, and African American, and 67% were receiving government assistance. Also, 33% were nulliparous; 54% had preterm labor; and 14.5% had multiple gestations.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded trial. Women at high risk for preterm delivery who received an initial course of corticosteroids and had not delivered in 1 week were randomized to receive either betamethasone 12 mg twice in 24 hours every week until 34 weeks or similarly administered placebo. Analysis was by intention to treat, using chi-square tests and t tests with assessment of study site as a potential confounder. The study was halted after 502 of a planned 1000 patients were recruited, due to emerging evidence that weekly corticosteroids might produce long-term neurologic sequelae. The methodology of this study was strong. The major weakness was lack of statistical power.

OUTCOMES MEASURED: The primary outcome was composite neonatal morbidity (including severe RDS, BPD and IVH, periventricular leukomalacia, sepsis, NEC, or death). Secondary outcomes included each individual outcome, maternal side effects, and clinical course. Utilization, cost, and patient satisfaction were not addressed.

RESULTS: The groups were similar at baseline and follow up was 97%. There was no significant difference in composite morbidity between the weekly course group and the single-course group. Exploratory analysis showed that weekly corticosteroids decreased severe RDS (15.3% vs 24.1%; P=.01), but there also a trend toward an increased risk of severe IVH in the weekly course group (7.6% vs 2.0%; P=.06). The weekly course group had shorter time to delivery (5.0 vs 5.8 weeks; P=.02) and a trend towards more chorioamnionitis (24.1% vs 17.8%; P=.09). There was no significant difference between the 2 treatment regimens in endometritis, wound infections, hemorrhage, or length of stay.

ABSTRACT

BACKGROUND: Current use of cervical spine (C-spine) radiography for alert and stable trauma patients is highly variable and expensive in practice. A recent clinical decision rule to identify low-risk patients was accurate in distinguishing those who would not need radiography (high sensitivity) but would result in many patients being unnecessarily imaged (low specificity).¹ The originators of the Ottawa Ankle and Knee rules have created a decision rule for use of C-spine radiography.

POPULATION STUDIED: The study enrolled patients 16 years and older who sustained acute blunt trauma to the head or neck and presented to an emergency department (ED) of 10 large Canadian hospitals. Patients had to be completely alert with normal vital signs. They either had to report neck pain or be nonambulatory with visible injury above the clavicles after a dangerous mechanism of injury. Patients were not studied if they were injured more than 48 hours before presentation, were returning for reassessment of the same injury, were pregnant, or had penetrating trauma, acute paralysis, or known vertebral disease.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which physicians determined 20 standardized clinical findings from the history and physical examination. The physician would then decide whether to obtain C-spine radiography; if no X-ray was obtained, a structured telephone interview 14 days later determined whether a clinically important C-spine injury had taken place. Clinical findings were then analyzed for their association with significant C-spine injuries. Although the study attempted to enroll consecutive patients, 3281 of 12,782 eligible patients were not enrolled for unclear reasons, and 577 patients could not be contacted by telephone for follow-up.

OUTCOMES MEASURED: The primary outcome measure was clinically important C-spine injury, defined as a fracture, dislocation, or ligamentous instability demonstrated by diagnostic imaging.

RESULTS: Approximately 69% of patients underwent C-spine radiography, and 31% underwent the 14-day follow-up phone interview. A total of 151 (1.7%) were determined to have a clinically important C-spine injury. No patients who did not undergo radiography were found to have important injuries 14 days later.

ABSTRACT

BACKGROUND: Current use of cervical spine (C-spine) radiography for alert and stable trauma patients is highly variable and expensive in practice. A recent clinical decision rule to identify low-risk patients was accurate in distinguishing those who would not need radiography (high sensitivity) but would result in many patients being unnecessarily imaged (low specificity).¹ The originators of the Ottawa Ankle and Knee rules have created a decision rule for use of C-spine radiography.

POPULATION STUDIED: The study enrolled patients 16 years and older who sustained acute blunt trauma to the head or neck and presented to an emergency department (ED) of 10 large Canadian hospitals. Patients had to be completely alert with normal vital signs. They either had to report neck pain or be nonambulatory with visible injury above the clavicles after a dangerous mechanism of injury. Patients were not studied if they were injured more than 48 hours before presentation, were returning for reassessment of the same injury, were pregnant, or had penetrating trauma, acute paralysis, or known vertebral disease.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which physicians determined 20 standardized clinical findings from the history and physical examination. The physician would then decide whether to obtain C-spine radiography; if no X-ray was obtained, a structured telephone interview 14 days later determined whether a clinically important C-spine injury had taken place. Clinical findings were then analyzed for their association with significant C-spine injuries. Although the study attempted to enroll consecutive patients, 3281 of 12,782 eligible patients were not enrolled for unclear reasons, and 577 patients could not be contacted by telephone for follow-up.

OUTCOMES MEASURED: The primary outcome measure was clinically important C-spine injury, defined as a fracture, dislocation, or ligamentous instability demonstrated by diagnostic imaging.

RESULTS: Approximately 69% of patients underwent C-spine radiography, and 31% underwent the 14-day follow-up phone interview. A total of 151 (1.7%) were determined to have a clinically important C-spine injury. No patients who did not undergo radiography were found to have important injuries 14 days later.

ABSTRACT

BACKGROUND: Current use of cervical spine (C-spine) radiography for alert and stable trauma patients is highly variable and expensive in practice. A recent clinical decision rule to identify low-risk patients was accurate in distinguishing those who would not need radiography (high sensitivity) but would result in many patients being unnecessarily imaged (low specificity).¹ The originators of the Ottawa Ankle and Knee rules have created a decision rule for use of C-spine radiography.

POPULATION STUDIED: The study enrolled patients 16 years and older who sustained acute blunt trauma to the head or neck and presented to an emergency department (ED) of 10 large Canadian hospitals. Patients had to be completely alert with normal vital signs. They either had to report neck pain or be nonambulatory with visible injury above the clavicles after a dangerous mechanism of injury. Patients were not studied if they were injured more than 48 hours before presentation, were returning for reassessment of the same injury, were pregnant, or had penetrating trauma, acute paralysis, or known vertebral disease.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which physicians determined 20 standardized clinical findings from the history and physical examination. The physician would then decide whether to obtain C-spine radiography; if no X-ray was obtained, a structured telephone interview 14 days later determined whether a clinically important C-spine injury had taken place. Clinical findings were then analyzed for their association with significant C-spine injuries. Although the study attempted to enroll consecutive patients, 3281 of 12,782 eligible patients were not enrolled for unclear reasons, and 577 patients could not be contacted by telephone for follow-up.

OUTCOMES MEASURED: The primary outcome measure was clinically important C-spine injury, defined as a fracture, dislocation, or ligamentous instability demonstrated by diagnostic imaging.

RESULTS: Approximately 69% of patients underwent C-spine radiography, and 31% underwent the 14-day follow-up phone interview. A total of 151 (1.7%) were determined to have a clinically important C-spine injury. No patients who did not undergo radiography were found to have important injuries 14 days later.

ABSTRACT

BACKGROUND: It has not been established whether antihypertensive agents provide a benefit beyond their blood pressure lowering effects. The investigators conducted a meta-analysis to determine whether old or new antihypertensive agents are more effective in preventing cardiovascular complications.

POPULATION STUDIED: The investigators included 9 studies enrolling 62,605 middle-aged patients (53-76 years) with a mean blood pressure at entry ranging from 145 to 194 mm Hg systolic and 83 to 106 mm Hg diastolic. The proportion of women ranged from 22% to 67%, and the proportion of patients with cardiovascular complications and diabetes varied (4% to 45% and 4% to 100%, respectively).

STUDY DESIGN AND VALIDITY: The meta-analysis compared older antihypertensive agents (β-blockers and diuretics) with new antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, and (β-blockers) for the prevention of cardiovascular complications. All studies were randomized controlled trials, published in peer-reviewed journals, included an assessment of blood pressure and cardiovascular events, were at least 2 years in duration, and enrolled at least 100 patients.

OUTCOMES MEASURED: The researchers determined cardiovascular mortality, cardiovascular events, fatal and nonfatal stroke, fatal and nonfatal myocardial infarction (MI), fatal and nonfatal congestive heart failure (CHF) rates with old versus new antihypertensive agents.

RESULTS: The new antihypertensive agents were as effective as the old antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. Calcium channel blockers provided more reduction in the risk of stroke than the older antihypertensive agents (absolute risk reduction [ARR]=13.5%, P <.03; number needed to treat [NNT]=7) but were associated with an increase in risk of fatal and nonfatal MI (absolute risk increase [ARI]=19.2%, P <.01; number needed to harm [NNH]=5). Older antihypertensive agents were more effective in preventing cardiovascular events (ARR=11.2%, P <.001; NNT=9). Newer antihypertensive agents were less effective in preventing fatal and nonfatal CHF (ARI=52.4%, P <.001; NNH=2), but this result was attributed to the higher risk of events with the (β-blocker doxazosin compared with the diuretic, chlorthalidone, in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial.

ABSTRACT

BACKGROUND: It has not been established whether antihypertensive agents provide a benefit beyond their blood pressure lowering effects. The investigators conducted a meta-analysis to determine whether old or new antihypertensive agents are more effective in preventing cardiovascular complications.

POPULATION STUDIED: The investigators included 9 studies enrolling 62,605 middle-aged patients (53-76 years) with a mean blood pressure at entry ranging from 145 to 194 mm Hg systolic and 83 to 106 mm Hg diastolic. The proportion of women ranged from 22% to 67%, and the proportion of patients with cardiovascular complications and diabetes varied (4% to 45% and 4% to 100%, respectively).

STUDY DESIGN AND VALIDITY: The meta-analysis compared older antihypertensive agents (β-blockers and diuretics) with new antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, and (β-blockers) for the prevention of cardiovascular complications. All studies were randomized controlled trials, published in peer-reviewed journals, included an assessment of blood pressure and cardiovascular events, were at least 2 years in duration, and enrolled at least 100 patients.

OUTCOMES MEASURED: The researchers determined cardiovascular mortality, cardiovascular events, fatal and nonfatal stroke, fatal and nonfatal myocardial infarction (MI), fatal and nonfatal congestive heart failure (CHF) rates with old versus new antihypertensive agents.

RESULTS: The new antihypertensive agents were as effective as the old antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. Calcium channel blockers provided more reduction in the risk of stroke than the older antihypertensive agents (absolute risk reduction [ARR]=13.5%, P <.03; number needed to treat [NNT]=7) but were associated with an increase in risk of fatal and nonfatal MI (absolute risk increase [ARI]=19.2%, P <.01; number needed to harm [NNH]=5). Older antihypertensive agents were more effective in preventing cardiovascular events (ARR=11.2%, P <.001; NNT=9). Newer antihypertensive agents were less effective in preventing fatal and nonfatal CHF (ARI=52.4%, P <.001; NNH=2), but this result was attributed to the higher risk of events with the (β-blocker doxazosin compared with the diuretic, chlorthalidone, in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial.

ABSTRACT

BACKGROUND: It has not been established whether antihypertensive agents provide a benefit beyond their blood pressure lowering effects. The investigators conducted a meta-analysis to determine whether old or new antihypertensive agents are more effective in preventing cardiovascular complications.

POPULATION STUDIED: The investigators included 9 studies enrolling 62,605 middle-aged patients (53-76 years) with a mean blood pressure at entry ranging from 145 to 194 mm Hg systolic and 83 to 106 mm Hg diastolic. The proportion of women ranged from 22% to 67%, and the proportion of patients with cardiovascular complications and diabetes varied (4% to 45% and 4% to 100%, respectively).

STUDY DESIGN AND VALIDITY: The meta-analysis compared older antihypertensive agents (β-blockers and diuretics) with new antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, and (β-blockers) for the prevention of cardiovascular complications. All studies were randomized controlled trials, published in peer-reviewed journals, included an assessment of blood pressure and cardiovascular events, were at least 2 years in duration, and enrolled at least 100 patients.

OUTCOMES MEASURED: The researchers determined cardiovascular mortality, cardiovascular events, fatal and nonfatal stroke, fatal and nonfatal myocardial infarction (MI), fatal and nonfatal congestive heart failure (CHF) rates with old versus new antihypertensive agents.

RESULTS: The new antihypertensive agents were as effective as the old antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. Calcium channel blockers provided more reduction in the risk of stroke than the older antihypertensive agents (absolute risk reduction [ARR]=13.5%, P <.03; number needed to treat [NNT]=7) but were associated with an increase in risk of fatal and nonfatal MI (absolute risk increase [ARI]=19.2%, P <.01; number needed to harm [NNH]=5). Older antihypertensive agents were more effective in preventing cardiovascular events (ARR=11.2%, P <.001; NNT=9). Newer antihypertensive agents were less effective in preventing fatal and nonfatal CHF (ARI=52.4%, P <.001; NNH=2), but this result was attributed to the higher risk of events with the (β-blocker doxazosin compared with the diuretic, chlorthalidone, in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial.