Q&A

ABSTRACT

BACKGROUND: Group B streptococcal (GBS) infection contributes significantly to neonatal morbidity and mortality. In 1996, the guidelines put forward by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention (CDC) recommended that prenatal care providers adopt either a “screening” or “risk-based” approach to guide intrapartum antibiotic prophylaxis for neonatal early-onset GBS infection. The efficacy of these 2 alternative approaches in clinical practice was compared in this population-based study.

POPULATION STUDIED: A total of 5144 birth records (including 312 cases of early-onset GBS disease) were randomly selected from 629,912 live birth records in 8 geographic areas monitored by the CDC during 1998 through 1999. The screened and risk-based groups were similar, but the risk-based group had a statistically significant greater number of Hispanics, women with inadequate prenatal care, and preterm deliveries. The screened group had a higher proportion of women with GBS bacteriuria and women with a history of previously delivering a GBS-infected neonate.

STUDY DESIGN AND VALIDITY: In this retrospective cohort study, the authors compared screening and risk-based approaches for prevention of neonatal GBS infection. At least 500 records from each CDC surveillance area were included. All GBS-infected neonates were included in the sample. The sample was stratified by surveillance area, year, and hospital, and each record was given a constant statistical weight based on the inverse of its probability of selection. This weight was adjusted to account for records without charts and for preterm births, ensuring that the number of preterm births was representative of the number in the general population. Abstractors blinded to infant GBS status gathered record information. Women who had a documented GBS culture at least 2 days prior to delivery were included in the screened group, and the remaining women were placed in the risk-based group. Univariate and multivariate analyses were used in comparing the groups, with the infant disease status as the outcome variable.

OUTCOMES MEASURED: The primary outcome measured was early-onset invasive GBS infection in neonates. Abstracters also recorded information on maternal demographics, prenatal care, GBS screening, risk factors for GBS infection, intrapartum antibiotic administration, and gestational age at birth.

RESULTS: The adjusted relative risk of neonatal infection in the screened group compared with the risk-based group was 0.46 (95% confidence interval [CI], 0.36–0.60). Intrapartum fever and a history of a previous infant with early GBS disease were the strongest predictors of GBS disease in both univariate and multivariate analyses. Women in the screened group who had positive culture results were much more likely to receive antibiotic prophylaxis than women in the risk-based group who had risk factors (89% vs 61%, P < .001). However, even with projected perfect administration in the risk-based group, the incidence of GBS disease would still be less in the screened group (0.32 vs 0.44 per 1000 live births). In addition, with perfect implementation of either preventive strategy, the anticipated overall rate of antibiotic use would be similar (31% in the screened group vs 29% in the risk-based group).

ABSTRACT

BACKGROUND: Group B streptococcal (GBS) infection contributes significantly to neonatal morbidity and mortality. In 1996, the guidelines put forward by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention (CDC) recommended that prenatal care providers adopt either a “screening” or “risk-based” approach to guide intrapartum antibiotic prophylaxis for neonatal early-onset GBS infection. The efficacy of these 2 alternative approaches in clinical practice was compared in this population-based study.

POPULATION STUDIED: A total of 5144 birth records (including 312 cases of early-onset GBS disease) were randomly selected from 629,912 live birth records in 8 geographic areas monitored by the CDC during 1998 through 1999. The screened and risk-based groups were similar, but the risk-based group had a statistically significant greater number of Hispanics, women with inadequate prenatal care, and preterm deliveries. The screened group had a higher proportion of women with GBS bacteriuria and women with a history of previously delivering a GBS-infected neonate.

STUDY DESIGN AND VALIDITY: In this retrospective cohort study, the authors compared screening and risk-based approaches for prevention of neonatal GBS infection. At least 500 records from each CDC surveillance area were included. All GBS-infected neonates were included in the sample. The sample was stratified by surveillance area, year, and hospital, and each record was given a constant statistical weight based on the inverse of its probability of selection. This weight was adjusted to account for records without charts and for preterm births, ensuring that the number of preterm births was representative of the number in the general population. Abstractors blinded to infant GBS status gathered record information. Women who had a documented GBS culture at least 2 days prior to delivery were included in the screened group, and the remaining women were placed in the risk-based group. Univariate and multivariate analyses were used in comparing the groups, with the infant disease status as the outcome variable.

OUTCOMES MEASURED: The primary outcome measured was early-onset invasive GBS infection in neonates. Abstracters also recorded information on maternal demographics, prenatal care, GBS screening, risk factors for GBS infection, intrapartum antibiotic administration, and gestational age at birth.

RESULTS: The adjusted relative risk of neonatal infection in the screened group compared with the risk-based group was 0.46 (95% confidence interval [CI], 0.36–0.60). Intrapartum fever and a history of a previous infant with early GBS disease were the strongest predictors of GBS disease in both univariate and multivariate analyses. Women in the screened group who had positive culture results were much more likely to receive antibiotic prophylaxis than women in the risk-based group who had risk factors (89% vs 61%, P < .001). However, even with projected perfect administration in the risk-based group, the incidence of GBS disease would still be less in the screened group (0.32 vs 0.44 per 1000 live births). In addition, with perfect implementation of either preventive strategy, the anticipated overall rate of antibiotic use would be similar (31% in the screened group vs 29% in the risk-based group).

ABSTRACT

BACKGROUND: Group B streptococcal (GBS) infection contributes significantly to neonatal morbidity and mortality. In 1996, the guidelines put forward by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention (CDC) recommended that prenatal care providers adopt either a “screening” or “risk-based” approach to guide intrapartum antibiotic prophylaxis for neonatal early-onset GBS infection. The efficacy of these 2 alternative approaches in clinical practice was compared in this population-based study.

POPULATION STUDIED: A total of 5144 birth records (including 312 cases of early-onset GBS disease) were randomly selected from 629,912 live birth records in 8 geographic areas monitored by the CDC during 1998 through 1999. The screened and risk-based groups were similar, but the risk-based group had a statistically significant greater number of Hispanics, women with inadequate prenatal care, and preterm deliveries. The screened group had a higher proportion of women with GBS bacteriuria and women with a history of previously delivering a GBS-infected neonate.

STUDY DESIGN AND VALIDITY: In this retrospective cohort study, the authors compared screening and risk-based approaches for prevention of neonatal GBS infection. At least 500 records from each CDC surveillance area were included. All GBS-infected neonates were included in the sample. The sample was stratified by surveillance area, year, and hospital, and each record was given a constant statistical weight based on the inverse of its probability of selection. This weight was adjusted to account for records without charts and for preterm births, ensuring that the number of preterm births was representative of the number in the general population. Abstractors blinded to infant GBS status gathered record information. Women who had a documented GBS culture at least 2 days prior to delivery were included in the screened group, and the remaining women were placed in the risk-based group. Univariate and multivariate analyses were used in comparing the groups, with the infant disease status as the outcome variable.

OUTCOMES MEASURED: The primary outcome measured was early-onset invasive GBS infection in neonates. Abstracters also recorded information on maternal demographics, prenatal care, GBS screening, risk factors for GBS infection, intrapartum antibiotic administration, and gestational age at birth.

RESULTS: The adjusted relative risk of neonatal infection in the screened group compared with the risk-based group was 0.46 (95% confidence interval [CI], 0.36–0.60). Intrapartum fever and a history of a previous infant with early GBS disease were the strongest predictors of GBS disease in both univariate and multivariate analyses. Women in the screened group who had positive culture results were much more likely to receive antibiotic prophylaxis than women in the risk-based group who had risk factors (89% vs 61%, P < .001). However, even with projected perfect administration in the risk-based group, the incidence of GBS disease would still be less in the screened group (0.32 vs 0.44 per 1000 live births). In addition, with perfect implementation of either preventive strategy, the anticipated overall rate of antibiotic use would be similar (31% in the screened group vs 29% in the risk-based group).

ABSTRACT

BACKGROUND: About half of syncopal episodes are vasovagal reactions. Empiric treatment with β-blockers is a common practice based on physiologic mechanisms of vasovagal syncope. Only 3 prospective, randomized controlled trials have been done to compare a β-blocker (atenolol) with placebo; no study showed reduced syncopal episodes. No studies have been published on β-blockers other than atenolol.

POPULATION STUDIED: The authors enrolled 30 consecutive patients with recurrent vasovagal syncope. The mean age of the subjects was 41 years; 17 (57%) were women. Investigators defined recurrent vasovagal syncope as at least 2 episodes in the past 3 months and a positive tilt test response. Patients had normal cardiovascular examinations and no electrocardiographic changes. Patients were excluded who had known or suspected autonomic failure (including diabetes), hypertension, chronic obstructive pulmonary disease, or peripheral vascular disease. Patients were recruited from an outpatient cardiology setting, potentially representing a different population than encountered in many primary care settings.

STUDY DESIGN AND VALIDITY: This study was an unblinded, crossover placebo-controlled trial. Patients were assigned to receive 3 drugs in random order for 3 months each. Study drugs were the maximum tolerated dose of propranolol (Inderal) 20 to 40 mg 3 times daily, nadolol (Corgard) 40 to 80 mg once daily, and placebo 1 capsule once daily. Investigators were not blinded but patients were. However, patients took propranolol 3 times daily compared with once daily for placebo and nadolol. To minimize the effect of dosing frequency, investigators advised patients that frequency had no relationship with efficacy. Concealed allocation was not performed. All 30 patients completed the study, although 1 patient withdrew from propranolol therapy due to fatigue. Results were analyzed by intention to treat.

OUTCOMES MEASURED: The primary outcome measured was the number of syncopal and presyncopal events during each study drug’s 3-month period. Additionally, patients’ assessed their quality of life and reported which therapies they preferred. Quality of life was scored from 0 to 4 based on vasovagal symptoms, drug side effects, and personal well being during therapy (0 = very dissatisfied and 4 = excellent).

RESULTS: Overall, no difference was noted in the number of syncopal episodes or quality of life scores during the 3 study periods. Propranolol, nadolol, and placebo equally improved outcomes as compared with baseline (0.25, 0.25, and 0.5 episodes during 3 months respectively vs 3.4 episodes per 3 months; P < .0001). Similar benefits were seen for presyncopal episodes (2.1, 1.3, and 2.6 episodes during 3 months, respectively vs 9.1 episodes per 3 months; P < .0001). Patients’ quality of life scores improved with propranolol, nadolol, and placebo as compared with baseline (3.1, 3.5, and 3.4 on a scale of 4, respectively vs 1.5; P < .0001). At the conclusion of the study, 4 patients preferred nadolol, 2 preferred placebo, and 3 preferred propranolol. Five patients were dissatisfied with propranolol due to fatigue. The remaining 70% of patients were satisfied with all 3 regimens.

ABSTRACT

BACKGROUND: About half of syncopal episodes are vasovagal reactions. Empiric treatment with β-blockers is a common practice based on physiologic mechanisms of vasovagal syncope. Only 3 prospective, randomized controlled trials have been done to compare a β-blocker (atenolol) with placebo; no study showed reduced syncopal episodes. No studies have been published on β-blockers other than atenolol.

POPULATION STUDIED: The authors enrolled 30 consecutive patients with recurrent vasovagal syncope. The mean age of the subjects was 41 years; 17 (57%) were women. Investigators defined recurrent vasovagal syncope as at least 2 episodes in the past 3 months and a positive tilt test response. Patients had normal cardiovascular examinations and no electrocardiographic changes. Patients were excluded who had known or suspected autonomic failure (including diabetes), hypertension, chronic obstructive pulmonary disease, or peripheral vascular disease. Patients were recruited from an outpatient cardiology setting, potentially representing a different population than encountered in many primary care settings.

STUDY DESIGN AND VALIDITY: This study was an unblinded, crossover placebo-controlled trial. Patients were assigned to receive 3 drugs in random order for 3 months each. Study drugs were the maximum tolerated dose of propranolol (Inderal) 20 to 40 mg 3 times daily, nadolol (Corgard) 40 to 80 mg once daily, and placebo 1 capsule once daily. Investigators were not blinded but patients were. However, patients took propranolol 3 times daily compared with once daily for placebo and nadolol. To minimize the effect of dosing frequency, investigators advised patients that frequency had no relationship with efficacy. Concealed allocation was not performed. All 30 patients completed the study, although 1 patient withdrew from propranolol therapy due to fatigue. Results were analyzed by intention to treat.

OUTCOMES MEASURED: The primary outcome measured was the number of syncopal and presyncopal events during each study drug’s 3-month period. Additionally, patients’ assessed their quality of life and reported which therapies they preferred. Quality of life was scored from 0 to 4 based on vasovagal symptoms, drug side effects, and personal well being during therapy (0 = very dissatisfied and 4 = excellent).

RESULTS: Overall, no difference was noted in the number of syncopal episodes or quality of life scores during the 3 study periods. Propranolol, nadolol, and placebo equally improved outcomes as compared with baseline (0.25, 0.25, and 0.5 episodes during 3 months respectively vs 3.4 episodes per 3 months; P < .0001). Similar benefits were seen for presyncopal episodes (2.1, 1.3, and 2.6 episodes during 3 months, respectively vs 9.1 episodes per 3 months; P < .0001). Patients’ quality of life scores improved with propranolol, nadolol, and placebo as compared with baseline (3.1, 3.5, and 3.4 on a scale of 4, respectively vs 1.5; P < .0001). At the conclusion of the study, 4 patients preferred nadolol, 2 preferred placebo, and 3 preferred propranolol. Five patients were dissatisfied with propranolol due to fatigue. The remaining 70% of patients were satisfied with all 3 regimens.

ABSTRACT

BACKGROUND: About half of syncopal episodes are vasovagal reactions. Empiric treatment with β-blockers is a common practice based on physiologic mechanisms of vasovagal syncope. Only 3 prospective, randomized controlled trials have been done to compare a β-blocker (atenolol) with placebo; no study showed reduced syncopal episodes. No studies have been published on β-blockers other than atenolol.

POPULATION STUDIED: The authors enrolled 30 consecutive patients with recurrent vasovagal syncope. The mean age of the subjects was 41 years; 17 (57%) were women. Investigators defined recurrent vasovagal syncope as at least 2 episodes in the past 3 months and a positive tilt test response. Patients had normal cardiovascular examinations and no electrocardiographic changes. Patients were excluded who had known or suspected autonomic failure (including diabetes), hypertension, chronic obstructive pulmonary disease, or peripheral vascular disease. Patients were recruited from an outpatient cardiology setting, potentially representing a different population than encountered in many primary care settings.

STUDY DESIGN AND VALIDITY: This study was an unblinded, crossover placebo-controlled trial. Patients were assigned to receive 3 drugs in random order for 3 months each. Study drugs were the maximum tolerated dose of propranolol (Inderal) 20 to 40 mg 3 times daily, nadolol (Corgard) 40 to 80 mg once daily, and placebo 1 capsule once daily. Investigators were not blinded but patients were. However, patients took propranolol 3 times daily compared with once daily for placebo and nadolol. To minimize the effect of dosing frequency, investigators advised patients that frequency had no relationship with efficacy. Concealed allocation was not performed. All 30 patients completed the study, although 1 patient withdrew from propranolol therapy due to fatigue. Results were analyzed by intention to treat.

OUTCOMES MEASURED: The primary outcome measured was the number of syncopal and presyncopal events during each study drug’s 3-month period. Additionally, patients’ assessed their quality of life and reported which therapies they preferred. Quality of life was scored from 0 to 4 based on vasovagal symptoms, drug side effects, and personal well being during therapy (0 = very dissatisfied and 4 = excellent).

RESULTS: Overall, no difference was noted in the number of syncopal episodes or quality of life scores during the 3 study periods. Propranolol, nadolol, and placebo equally improved outcomes as compared with baseline (0.25, 0.25, and 0.5 episodes during 3 months respectively vs 3.4 episodes per 3 months; P < .0001). Similar benefits were seen for presyncopal episodes (2.1, 1.3, and 2.6 episodes during 3 months, respectively vs 9.1 episodes per 3 months; P < .0001). Patients’ quality of life scores improved with propranolol, nadolol, and placebo as compared with baseline (3.1, 3.5, and 3.4 on a scale of 4, respectively vs 1.5; P < .0001). At the conclusion of the study, 4 patients preferred nadolol, 2 preferred placebo, and 3 preferred propranolol. Five patients were dissatisfied with propranolol due to fatigue. The remaining 70% of patients were satisfied with all 3 regimens.

ABSTRACT

BACKGROUND: Endometrial biopsy has been reported to sample only a small percentage of the endometrial tissue with a lower sensitivity for focal and pedunculated lesions. It has been suggested that failure to diagnose intracavity lesions could be reduced or even eliminated by complementing endometrial sampling with outpatient hysteroscopy. The authors of this study assessed whether adding hysteroscopy to the evaluation routinely would offer clinical benefit.

POPULATION STUDIED: Ten consulting gynecologists recruited 370 premenopausal women who were referred to an outpatient gynecology clinic for abnormal uterine bleeding during a 3-year period. The women were eligible if they had a uterine size of 12 weeks or less by bimanual examination and if the attending gynecologist determined that endometrial sampling was required for diagnostic purposes.

STUDY DESIGN AND VALIDITY: In this randomized controlled trial, neither patients nor physicians were blinded to treatment group. It is not clear whether blinded evaluators performed some outcome assessments. Women randomized to endometrial biopsy underwent the procedure during their initial clinic visit using a 3-mm Pipelle biopsy kit in standard fashion.

OUTCOMES MEASURED: The primary outcome was surgical intervention rate, as determined by chart review. Secondary outcomes included procedural success and acceptability, intrauterine pathology identified, and clinical management.

RESULTS: No difference was noted in hysterectomy or endometrial ablation rates between the 2 groups. Procedural acceptability was no different across 11 of 12 parameters, with the only reported significant difference being that women undergoing hysteroscopy were “happier” than patients undergoing just endometrial biopsy. Reported pain levels as measured by the McGill Pain Questionnaire were no different for the two procedures and only slightly greater than the pain estimated for a Pap smear or vaginal examination.

ABSTRACT

BACKGROUND: Endometrial biopsy has been reported to sample only a small percentage of the endometrial tissue with a lower sensitivity for focal and pedunculated lesions. It has been suggested that failure to diagnose intracavity lesions could be reduced or even eliminated by complementing endometrial sampling with outpatient hysteroscopy. The authors of this study assessed whether adding hysteroscopy to the evaluation routinely would offer clinical benefit.

POPULATION STUDIED: Ten consulting gynecologists recruited 370 premenopausal women who were referred to an outpatient gynecology clinic for abnormal uterine bleeding during a 3-year period. The women were eligible if they had a uterine size of 12 weeks or less by bimanual examination and if the attending gynecologist determined that endometrial sampling was required for diagnostic purposes.

STUDY DESIGN AND VALIDITY: In this randomized controlled trial, neither patients nor physicians were blinded to treatment group. It is not clear whether blinded evaluators performed some outcome assessments. Women randomized to endometrial biopsy underwent the procedure during their initial clinic visit using a 3-mm Pipelle biopsy kit in standard fashion.

OUTCOMES MEASURED: The primary outcome was surgical intervention rate, as determined by chart review. Secondary outcomes included procedural success and acceptability, intrauterine pathology identified, and clinical management.

RESULTS: No difference was noted in hysterectomy or endometrial ablation rates between the 2 groups. Procedural acceptability was no different across 11 of 12 parameters, with the only reported significant difference being that women undergoing hysteroscopy were “happier” than patients undergoing just endometrial biopsy. Reported pain levels as measured by the McGill Pain Questionnaire were no different for the two procedures and only slightly greater than the pain estimated for a Pap smear or vaginal examination.

ABSTRACT

BACKGROUND: Endometrial biopsy has been reported to sample only a small percentage of the endometrial tissue with a lower sensitivity for focal and pedunculated lesions. It has been suggested that failure to diagnose intracavity lesions could be reduced or even eliminated by complementing endometrial sampling with outpatient hysteroscopy. The authors of this study assessed whether adding hysteroscopy to the evaluation routinely would offer clinical benefit.

POPULATION STUDIED: Ten consulting gynecologists recruited 370 premenopausal women who were referred to an outpatient gynecology clinic for abnormal uterine bleeding during a 3-year period. The women were eligible if they had a uterine size of 12 weeks or less by bimanual examination and if the attending gynecologist determined that endometrial sampling was required for diagnostic purposes.

STUDY DESIGN AND VALIDITY: In this randomized controlled trial, neither patients nor physicians were blinded to treatment group. It is not clear whether blinded evaluators performed some outcome assessments. Women randomized to endometrial biopsy underwent the procedure during their initial clinic visit using a 3-mm Pipelle biopsy kit in standard fashion.

OUTCOMES MEASURED: The primary outcome was surgical intervention rate, as determined by chart review. Secondary outcomes included procedural success and acceptability, intrauterine pathology identified, and clinical management.

RESULTS: No difference was noted in hysterectomy or endometrial ablation rates between the 2 groups. Procedural acceptability was no different across 11 of 12 parameters, with the only reported significant difference being that women undergoing hysteroscopy were “happier” than patients undergoing just endometrial biopsy. Reported pain levels as measured by the McGill Pain Questionnaire were no different for the two procedures and only slightly greater than the pain estimated for a Pap smear or vaginal examination.

ABSTRACT

BACKGROUND: The diagnosis of a pulmonary embolism is challenging because of the potentially severe consequences of missing the condition and imaging test results that are often equivocal. Clinical decisions may be aided by a test for D-dimer, a fibrin degradation product usually increased in the blood of patients with thromboembolic disease. Laboratory advances have led to more rapid and practical detection techniques, such as the enzyme-linked immunosorbent assay (ELISA) method examined by this meta-analysis.

POPULATION STUDIED: The 11 prospective studies included in this meta-analysis involved 2126 patients (aged 54 to 81 years), more than 98% of whom were outpatients presenting with symptoms and signs suspicious for a pulmonary embolism. There were more women than men in the study population.

STUDY DESIGN AND VALIDITY: MEDLINE and EMBASE searches identified relevant titles and abstracts of published articles from 1980 through 2000, and the researchers also searched for unpublished work, screened the reference lists of articles, and contacted authors to identify other studies. All of the included studies had to be original prospective investigations of the ELISA D-dimer test enrolling at least 80% outpatients. Independent reviewers screened articles for quality of reference standards and generalizability. Reference standards for the diagnosis of a pulmonary embolism included a high-probability ventilation/perfusion scan, positive computerized tomographic scan, or positive lower extremity imaging. Acceptable standards for a negative diagnosis were normal or very low probability ventilation/perfusion scan or the absence of a thromboembolic event for 3 months or more.

OUTCOMES MEASURED: The primary results were the pooled sensitivity and specificity of the ELISA D-dimer test in detecting a pulmonary embolism. The authors reported pooled estimates of sensitivity and specificity for various combinations of studies, based on the quality of the studies, method of ELISA testing, age of patients, comorbid conditions, and symptom duration.

RESULTS: Pooling all 11 studies led to an overall sensitivity of 0.95 (95% confidence interval [CI], 0.90–0.98) and a specificity of 0.45 (95% CI, 0.90–0.98). The 5 studies that used the most rigorous reference standard protocols yielded a sensitivity of 0.90 and a specificity of 0.40. A higher pooled accuracy was found in the group of 8 studies with the most typical spectrum of outpatients (sensitivity and specificity of 0.97 and 0.48, respectively). In general, the high sensitivity and low specificity of the ELISA D-dimer test will lead to the detection of a pulmonary embolism most of the time when the condition is present, but false-positive results are common. Several clinical scenarios may decrease the test’s accuracy. In the one small study of patients aged 70 years or older, the sensitivity was perfect (1.00) but the specificity was low (0.14). In another study examining patients whose symptoms lasted 4 days or more, the sensitivity fell to 0.73 and specificity was 0.33. Both of these studies suggest more consideration be given to other conditions, such as infection, cancer, or inflammatory arthritides, which could elevate D-dimer levels in these patient populations.

ABSTRACT

BACKGROUND: The diagnosis of a pulmonary embolism is challenging because of the potentially severe consequences of missing the condition and imaging test results that are often equivocal. Clinical decisions may be aided by a test for D-dimer, a fibrin degradation product usually increased in the blood of patients with thromboembolic disease. Laboratory advances have led to more rapid and practical detection techniques, such as the enzyme-linked immunosorbent assay (ELISA) method examined by this meta-analysis.

POPULATION STUDIED: The 11 prospective studies included in this meta-analysis involved 2126 patients (aged 54 to 81 years), more than 98% of whom were outpatients presenting with symptoms and signs suspicious for a pulmonary embolism. There were more women than men in the study population.

STUDY DESIGN AND VALIDITY: MEDLINE and EMBASE searches identified relevant titles and abstracts of published articles from 1980 through 2000, and the researchers also searched for unpublished work, screened the reference lists of articles, and contacted authors to identify other studies. All of the included studies had to be original prospective investigations of the ELISA D-dimer test enrolling at least 80% outpatients. Independent reviewers screened articles for quality of reference standards and generalizability. Reference standards for the diagnosis of a pulmonary embolism included a high-probability ventilation/perfusion scan, positive computerized tomographic scan, or positive lower extremity imaging. Acceptable standards for a negative diagnosis were normal or very low probability ventilation/perfusion scan or the absence of a thromboembolic event for 3 months or more.

OUTCOMES MEASURED: The primary results were the pooled sensitivity and specificity of the ELISA D-dimer test in detecting a pulmonary embolism. The authors reported pooled estimates of sensitivity and specificity for various combinations of studies, based on the quality of the studies, method of ELISA testing, age of patients, comorbid conditions, and symptom duration.

RESULTS: Pooling all 11 studies led to an overall sensitivity of 0.95 (95% confidence interval [CI], 0.90–0.98) and a specificity of 0.45 (95% CI, 0.90–0.98). The 5 studies that used the most rigorous reference standard protocols yielded a sensitivity of 0.90 and a specificity of 0.40. A higher pooled accuracy was found in the group of 8 studies with the most typical spectrum of outpatients (sensitivity and specificity of 0.97 and 0.48, respectively). In general, the high sensitivity and low specificity of the ELISA D-dimer test will lead to the detection of a pulmonary embolism most of the time when the condition is present, but false-positive results are common. Several clinical scenarios may decrease the test’s accuracy. In the one small study of patients aged 70 years or older, the sensitivity was perfect (1.00) but the specificity was low (0.14). In another study examining patients whose symptoms lasted 4 days or more, the sensitivity fell to 0.73 and specificity was 0.33. Both of these studies suggest more consideration be given to other conditions, such as infection, cancer, or inflammatory arthritides, which could elevate D-dimer levels in these patient populations.

ABSTRACT

BACKGROUND: The diagnosis of a pulmonary embolism is challenging because of the potentially severe consequences of missing the condition and imaging test results that are often equivocal. Clinical decisions may be aided by a test for D-dimer, a fibrin degradation product usually increased in the blood of patients with thromboembolic disease. Laboratory advances have led to more rapid and practical detection techniques, such as the enzyme-linked immunosorbent assay (ELISA) method examined by this meta-analysis.

POPULATION STUDIED: The 11 prospective studies included in this meta-analysis involved 2126 patients (aged 54 to 81 years), more than 98% of whom were outpatients presenting with symptoms and signs suspicious for a pulmonary embolism. There were more women than men in the study population.

STUDY DESIGN AND VALIDITY: MEDLINE and EMBASE searches identified relevant titles and abstracts of published articles from 1980 through 2000, and the researchers also searched for unpublished work, screened the reference lists of articles, and contacted authors to identify other studies. All of the included studies had to be original prospective investigations of the ELISA D-dimer test enrolling at least 80% outpatients. Independent reviewers screened articles for quality of reference standards and generalizability. Reference standards for the diagnosis of a pulmonary embolism included a high-probability ventilation/perfusion scan, positive computerized tomographic scan, or positive lower extremity imaging. Acceptable standards for a negative diagnosis were normal or very low probability ventilation/perfusion scan or the absence of a thromboembolic event for 3 months or more.

OUTCOMES MEASURED: The primary results were the pooled sensitivity and specificity of the ELISA D-dimer test in detecting a pulmonary embolism. The authors reported pooled estimates of sensitivity and specificity for various combinations of studies, based on the quality of the studies, method of ELISA testing, age of patients, comorbid conditions, and symptom duration.

RESULTS: Pooling all 11 studies led to an overall sensitivity of 0.95 (95% confidence interval [CI], 0.90–0.98) and a specificity of 0.45 (95% CI, 0.90–0.98). The 5 studies that used the most rigorous reference standard protocols yielded a sensitivity of 0.90 and a specificity of 0.40. A higher pooled accuracy was found in the group of 8 studies with the most typical spectrum of outpatients (sensitivity and specificity of 0.97 and 0.48, respectively). In general, the high sensitivity and low specificity of the ELISA D-dimer test will lead to the detection of a pulmonary embolism most of the time when the condition is present, but false-positive results are common. Several clinical scenarios may decrease the test’s accuracy. In the one small study of patients aged 70 years or older, the sensitivity was perfect (1.00) but the specificity was low (0.14). In another study examining patients whose symptoms lasted 4 days or more, the sensitivity fell to 0.73 and specificity was 0.33. Both of these studies suggest more consideration be given to other conditions, such as infection, cancer, or inflammatory arthritides, which could elevate D-dimer levels in these patient populations.

ABSTRACT

BACKGROUND: Family physicians often evaluate patients with symptoms of possible carotid artery stenosis. The gold standard for diagnosis is digital subtraction angiography (DSA), an invasive procedure with rare but serious complications of stroke and death. In this study the authors assessed the diagnostic performance of contemporary noninvasive testing with duplex ultrasound (DUS) and magnetic resonance angiography (MRA) as compared with DSA.

POPULATION STUDIED: The investigators enrolled 350 consecutive patients with symptoms of possible carotid artery stenosis from 3 medical centers in the Netherlands. They excluded patients with contraindications to MRA such as claustrophobia or metal implants. The reasons for examination were varied: 42% had symptoms of transient ischemic attacks, 36% had symptoms of stroke, and 22% had symptoms of amaurosis fugax. The authors did not describe how these patients were referred. The average age of the patients was 67 years and 76% were male; 49% of the patients were current smokers, 49% had hypertension, and 34% had either angina or a history of myocardial infarction. Thus, although no information was given regarding the race and socioeconomic status, the patients seem similar to high-risk patients in a typical US family practice.

STUDY DESIGN AND VALIDITY: In this prospective study consecutive patients underwent DUS, MRA, and DSA examination within a maximum of 4 weeks to be evaluated for carotid stenosis. The degree of stenosis on DUS was estimated from peak systolic velocity. Digital subtraction angiography and MRA images were read by an observer unaware of clinical information and the results of other tests. Severe stenosis was defined as 70% to 99% stenosis on DSA on the side of the symptoms and measured according to criteria of the North American Symptomatic Carotid Endarterectomy Trial. Digital ultrasound and MRA results were compared with results of DSA as a gold standard. Reproducibility of the estimate of stenosis was assessed by comparison of measurement by 2 independent observers on a subsample of 170 patients.

OUTCOMES MEASURED: Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for DUS and MRA. Kappa statistics estimated interobserver variability for MRA and DSA. Patient-oriented outcomes that were not addressed included cost, patient satisfaction, and side effects of DUS and MRA such as discomfort.

RESULTS: The prevalence of potentially operable severe stenosis was 46% and an additional 20% of the patients had total occlusion. For diagnosing severe stenosis, DUS had a sensitivity of 87.5% (95% confidence interval [CI], 82.1–92.9), a specificity of 75.7% (95% CI, 69.3–82.2), a negative predictive value of 87.7% (95% CI, 82.3–93.0), and a positive predictive value of 75.4% (95% CI, 68.9–82.0). Magnetic resonance angiography alone had a sensitivity of 92.2% (95% CI, 86.2–96.2), a specificity of 75.7% (95% CI, 68.6–82.5), a negative predictive value of 92.0% (95% CI, 85.8–96.1), and a positive predictive value of 76.3% (95% CI, 69.6–83.0). Both DUS and MRA tended to overestimate stenosis slightly. Digital ultrasound and MRA agreed on severe stenosis in 84% of the cases, but of these cases, DSA confirmed severe stenosis in only 81%. Kappa values (κ) for DSA and MRA were excellent (κ = 0.79 for each).

ABSTRACT

BACKGROUND: Family physicians often evaluate patients with symptoms of possible carotid artery stenosis. The gold standard for diagnosis is digital subtraction angiography (DSA), an invasive procedure with rare but serious complications of stroke and death. In this study the authors assessed the diagnostic performance of contemporary noninvasive testing with duplex ultrasound (DUS) and magnetic resonance angiography (MRA) as compared with DSA.

POPULATION STUDIED: The investigators enrolled 350 consecutive patients with symptoms of possible carotid artery stenosis from 3 medical centers in the Netherlands. They excluded patients with contraindications to MRA such as claustrophobia or metal implants. The reasons for examination were varied: 42% had symptoms of transient ischemic attacks, 36% had symptoms of stroke, and 22% had symptoms of amaurosis fugax. The authors did not describe how these patients were referred. The average age of the patients was 67 years and 76% were male; 49% of the patients were current smokers, 49% had hypertension, and 34% had either angina or a history of myocardial infarction. Thus, although no information was given regarding the race and socioeconomic status, the patients seem similar to high-risk patients in a typical US family practice.

STUDY DESIGN AND VALIDITY: In this prospective study consecutive patients underwent DUS, MRA, and DSA examination within a maximum of 4 weeks to be evaluated for carotid stenosis. The degree of stenosis on DUS was estimated from peak systolic velocity. Digital subtraction angiography and MRA images were read by an observer unaware of clinical information and the results of other tests. Severe stenosis was defined as 70% to 99% stenosis on DSA on the side of the symptoms and measured according to criteria of the North American Symptomatic Carotid Endarterectomy Trial. Digital ultrasound and MRA results were compared with results of DSA as a gold standard. Reproducibility of the estimate of stenosis was assessed by comparison of measurement by 2 independent observers on a subsample of 170 patients.

OUTCOMES MEASURED: Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for DUS and MRA. Kappa statistics estimated interobserver variability for MRA and DSA. Patient-oriented outcomes that were not addressed included cost, patient satisfaction, and side effects of DUS and MRA such as discomfort.

RESULTS: The prevalence of potentially operable severe stenosis was 46% and an additional 20% of the patients had total occlusion. For diagnosing severe stenosis, DUS had a sensitivity of 87.5% (95% confidence interval [CI], 82.1–92.9), a specificity of 75.7% (95% CI, 69.3–82.2), a negative predictive value of 87.7% (95% CI, 82.3–93.0), and a positive predictive value of 75.4% (95% CI, 68.9–82.0). Magnetic resonance angiography alone had a sensitivity of 92.2% (95% CI, 86.2–96.2), a specificity of 75.7% (95% CI, 68.6–82.5), a negative predictive value of 92.0% (95% CI, 85.8–96.1), and a positive predictive value of 76.3% (95% CI, 69.6–83.0). Both DUS and MRA tended to overestimate stenosis slightly. Digital ultrasound and MRA agreed on severe stenosis in 84% of the cases, but of these cases, DSA confirmed severe stenosis in only 81%. Kappa values (κ) for DSA and MRA were excellent (κ = 0.79 for each).

ABSTRACT

BACKGROUND: Family physicians often evaluate patients with symptoms of possible carotid artery stenosis. The gold standard for diagnosis is digital subtraction angiography (DSA), an invasive procedure with rare but serious complications of stroke and death. In this study the authors assessed the diagnostic performance of contemporary noninvasive testing with duplex ultrasound (DUS) and magnetic resonance angiography (MRA) as compared with DSA.

POPULATION STUDIED: The investigators enrolled 350 consecutive patients with symptoms of possible carotid artery stenosis from 3 medical centers in the Netherlands. They excluded patients with contraindications to MRA such as claustrophobia or metal implants. The reasons for examination were varied: 42% had symptoms of transient ischemic attacks, 36% had symptoms of stroke, and 22% had symptoms of amaurosis fugax. The authors did not describe how these patients were referred. The average age of the patients was 67 years and 76% were male; 49% of the patients were current smokers, 49% had hypertension, and 34% had either angina or a history of myocardial infarction. Thus, although no information was given regarding the race and socioeconomic status, the patients seem similar to high-risk patients in a typical US family practice.

STUDY DESIGN AND VALIDITY: In this prospective study consecutive patients underwent DUS, MRA, and DSA examination within a maximum of 4 weeks to be evaluated for carotid stenosis. The degree of stenosis on DUS was estimated from peak systolic velocity. Digital subtraction angiography and MRA images were read by an observer unaware of clinical information and the results of other tests. Severe stenosis was defined as 70% to 99% stenosis on DSA on the side of the symptoms and measured according to criteria of the North American Symptomatic Carotid Endarterectomy Trial. Digital ultrasound and MRA results were compared with results of DSA as a gold standard. Reproducibility of the estimate of stenosis was assessed by comparison of measurement by 2 independent observers on a subsample of 170 patients.

OUTCOMES MEASURED: Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for DUS and MRA. Kappa statistics estimated interobserver variability for MRA and DSA. Patient-oriented outcomes that were not addressed included cost, patient satisfaction, and side effects of DUS and MRA such as discomfort.

RESULTS: The prevalence of potentially operable severe stenosis was 46% and an additional 20% of the patients had total occlusion. For diagnosing severe stenosis, DUS had a sensitivity of 87.5% (95% confidence interval [CI], 82.1–92.9), a specificity of 75.7% (95% CI, 69.3–82.2), a negative predictive value of 87.7% (95% CI, 82.3–93.0), and a positive predictive value of 75.4% (95% CI, 68.9–82.0). Magnetic resonance angiography alone had a sensitivity of 92.2% (95% CI, 86.2–96.2), a specificity of 75.7% (95% CI, 68.6–82.5), a negative predictive value of 92.0% (95% CI, 85.8–96.1), and a positive predictive value of 76.3% (95% CI, 69.6–83.0). Both DUS and MRA tended to overestimate stenosis slightly. Digital ultrasound and MRA agreed on severe stenosis in 84% of the cases, but of these cases, DSA confirmed severe stenosis in only 81%. Kappa values (κ) for DSA and MRA were excellent (κ = 0.79 for each).

ABSTRACT

BACKGROUND: Severe behavior problems in children with autism interfere with treatment. These authors studied the efficacy and safety of risperidone to reduce behavioral problems in a small population of children with autism.

POPULATION STUDIED: The researchers studied 101 children with autistic disorder, as determined by semistructured interview. The children also had severe tantrums, aggression, or self-injurious behavior, or a combination of these behavioral problems. The children (82 boys and 19 girls), aged 5 to 17 years (mean age ± SD, 8.8 ± 2.7 years), weighed at least 15 kg, had a mental age of at least 18 months, and were free of serious medical disorders and other psychiatric disorders requiring medications. Children receiving psychotropic drugs for the treatment of aggressive behavior were not included. Children taking anticonvulsant agents for seizure control were included as long as the dose had not been changed for at least 4 weeks and the child had been seizure-free for the past 6 months.

STUDY DESIGN AND VALIDITY: The study was an 8-week, double-blind, randomized, placebo-controlled trial of risperidone. For children weighing 20 to 45 kg, the researchers started with an initial dose of 0.5 mg at bedtime, increasing the dose to 0.5 mg twice daily after 4 days, to a maximum of 1.0 mg in the morning and 1.5 mg in the evening by day 29. Children weighing less than 20 kg started with an initial dose of 0.25 mg per day, while those children who weighed more than 45 kg received a maximum dose of 1.5 mg in the morning and 2.0 mg in the evening. Each week 2 blinded clinicians evaluated the subjects: one who reviewed side effects and adjusted dose and a second who rated response to treatment.

OUTCOMES MEASURED: Primary outcome measures consisted of the irritability subscale of the Aberrant Behavior Checklist (ABC) (parent/caregiver rating) and the Clinical Global Impressions-Improvement (CGI-I) scale (clinician rating). A positive response was considered to be a 25% reduction in the irritability score combined with a rating of much improved or very much improved on the CGI-I scale. Adverse effects were also assessed through weekly monitoring of weight, vital signs, neurologic and other side effects. Other outcomes included the other subscales of the ABC.

RESULTS: Significantly more children treated with risperidone had a reduction in irritability score by at least 25% and a rating of much improved or very much improved on the CGI-I scale at the end of the 8-week trial (69% vs 12%, number needed to treat = 1.8). Side effects, which were expected and mild, included weight gain and appetite changes, dizziness, drooling, drowsiness, and fatigue. No extrapyramidal symptoms were observed during the study in either group, although tremor was more common in the intervention group (P = .06). Scores on other ABC subscales for stereotypy and hyperactivity also improved significantly.

ABSTRACT

BACKGROUND: Severe behavior problems in children with autism interfere with treatment. These authors studied the efficacy and safety of risperidone to reduce behavioral problems in a small population of children with autism.

POPULATION STUDIED: The researchers studied 101 children with autistic disorder, as determined by semistructured interview. The children also had severe tantrums, aggression, or self-injurious behavior, or a combination of these behavioral problems. The children (82 boys and 19 girls), aged 5 to 17 years (mean age ± SD, 8.8 ± 2.7 years), weighed at least 15 kg, had a mental age of at least 18 months, and were free of serious medical disorders and other psychiatric disorders requiring medications. Children receiving psychotropic drugs for the treatment of aggressive behavior were not included. Children taking anticonvulsant agents for seizure control were included as long as the dose had not been changed for at least 4 weeks and the child had been seizure-free for the past 6 months.

STUDY DESIGN AND VALIDITY: The study was an 8-week, double-blind, randomized, placebo-controlled trial of risperidone. For children weighing 20 to 45 kg, the researchers started with an initial dose of 0.5 mg at bedtime, increasing the dose to 0.5 mg twice daily after 4 days, to a maximum of 1.0 mg in the morning and 1.5 mg in the evening by day 29. Children weighing less than 20 kg started with an initial dose of 0.25 mg per day, while those children who weighed more than 45 kg received a maximum dose of 1.5 mg in the morning and 2.0 mg in the evening. Each week 2 blinded clinicians evaluated the subjects: one who reviewed side effects and adjusted dose and a second who rated response to treatment.

OUTCOMES MEASURED: Primary outcome measures consisted of the irritability subscale of the Aberrant Behavior Checklist (ABC) (parent/caregiver rating) and the Clinical Global Impressions-Improvement (CGI-I) scale (clinician rating). A positive response was considered to be a 25% reduction in the irritability score combined with a rating of much improved or very much improved on the CGI-I scale. Adverse effects were also assessed through weekly monitoring of weight, vital signs, neurologic and other side effects. Other outcomes included the other subscales of the ABC.

RESULTS: Significantly more children treated with risperidone had a reduction in irritability score by at least 25% and a rating of much improved or very much improved on the CGI-I scale at the end of the 8-week trial (69% vs 12%, number needed to treat = 1.8). Side effects, which were expected and mild, included weight gain and appetite changes, dizziness, drooling, drowsiness, and fatigue. No extrapyramidal symptoms were observed during the study in either group, although tremor was more common in the intervention group (P = .06). Scores on other ABC subscales for stereotypy and hyperactivity also improved significantly.

ABSTRACT

BACKGROUND: Severe behavior problems in children with autism interfere with treatment. These authors studied the efficacy and safety of risperidone to reduce behavioral problems in a small population of children with autism.

POPULATION STUDIED: The researchers studied 101 children with autistic disorder, as determined by semistructured interview. The children also had severe tantrums, aggression, or self-injurious behavior, or a combination of these behavioral problems. The children (82 boys and 19 girls), aged 5 to 17 years (mean age ± SD, 8.8 ± 2.7 years), weighed at least 15 kg, had a mental age of at least 18 months, and were free of serious medical disorders and other psychiatric disorders requiring medications. Children receiving psychotropic drugs for the treatment of aggressive behavior were not included. Children taking anticonvulsant agents for seizure control were included as long as the dose had not been changed for at least 4 weeks and the child had been seizure-free for the past 6 months.

STUDY DESIGN AND VALIDITY: The study was an 8-week, double-blind, randomized, placebo-controlled trial of risperidone. For children weighing 20 to 45 kg, the researchers started with an initial dose of 0.5 mg at bedtime, increasing the dose to 0.5 mg twice daily after 4 days, to a maximum of 1.0 mg in the morning and 1.5 mg in the evening by day 29. Children weighing less than 20 kg started with an initial dose of 0.25 mg per day, while those children who weighed more than 45 kg received a maximum dose of 1.5 mg in the morning and 2.0 mg in the evening. Each week 2 blinded clinicians evaluated the subjects: one who reviewed side effects and adjusted dose and a second who rated response to treatment.

OUTCOMES MEASURED: Primary outcome measures consisted of the irritability subscale of the Aberrant Behavior Checklist (ABC) (parent/caregiver rating) and the Clinical Global Impressions-Improvement (CGI-I) scale (clinician rating). A positive response was considered to be a 25% reduction in the irritability score combined with a rating of much improved or very much improved on the CGI-I scale. Adverse effects were also assessed through weekly monitoring of weight, vital signs, neurologic and other side effects. Other outcomes included the other subscales of the ABC.

RESULTS: Significantly more children treated with risperidone had a reduction in irritability score by at least 25% and a rating of much improved or very much improved on the CGI-I scale at the end of the 8-week trial (69% vs 12%, number needed to treat = 1.8). Side effects, which were expected and mild, included weight gain and appetite changes, dizziness, drooling, drowsiness, and fatigue. No extrapyramidal symptoms were observed during the study in either group, although tremor was more common in the intervention group (P = .06). Scores on other ABC subscales for stereotypy and hyperactivity also improved significantly.

ABSTRACT

BACKGROUND: One of the proposed benefits of postmenopausal hormone replacement therapy (HRT) is the prevention of coronary heart disease. This proposal is based on evidence from nonrandomized observational studies and intermediate outcomes such as improved lipid profiles. The possibility of harm from HRT has also been reported, particularly regarding breast cancer and thromboembolic disease. The Heart and Estrogen/progestin Replacement Study recently challenged the benefits of HRT, showing no overall protective effect on coronary heart disease (and an increased risk of harm in the first year of treatment) for women with prior coronary heart disease.

POPULATION STUDIED: The Women’s Health Initiative is a set of clinical trials with more than 160,000 women enrolled in studies of low-fat diet, calcium and vitamin D supplementation, and post-menopausal hormone use. This particular report focused on the trial of estrogen plus progestin in women with an intact uterus. A total of 16,608 post-menopausal women were randomized to receive either 1 daily tablet of conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg (Prempro) or placebo. Women were excluded if they had a history of breast cancer, other cancer within 10 years, hysterectomy, anemia, thrombocytopenia, alcoholism, or dementia. Ages ranged from 50 to 79 years (mean 63 years). Approximately 36% of the women were being treated for hypertension, 4.4% had diabetes, and 7.7% reported a history of cardiovascular disease.

STUDY DESIGN AND VALIDITY: This was a well-designed double-blind, randomized controlled trial with concealed allocation. Baseline characteristics were similar between groups. Follow-up was conducted 6 weeks after randomization, every 6 months with questionnaires, and annually with in-clinic visits. Intention-to-treat analysis was appropriate and would tend to find smaller differences between groups given the high dropout rates (42% in the HRT group and 38% in the placebo group). The trial was originally designed to last more than 8 years, but the independent safety monitoring board recommended stopping the trial when the difference in breast cancer rates exceeded a predetermined threshold and the global index was supportive of harm. When the trial was stopped in the spring of 2002, the average follow-up period was 5.2 years.

OUTCOMES MEASURED: The primary outcome measure was the rate of coronary heart disease, defined as acute myocardial infarction requiring overnight hospitalization, silent myocardial infarction determined from serial electrocardiograms, or coronary heart disease death. The secondary outcome measure was hip fracture rate. The primary adverse outcome measure was invasive breast cancer rate. Reported outcomes also included other cancers, total fractures, stroke, pulmonary embolism, deep vein thrombosis, and total mortality. A global index of outcomes was also calculated as a summary measure of risks and benefits. No measures of vasomotor symptoms or quality of life were reported.

RESULTS: Women in the HRT group had a higher annual incidence of coronary heart disease (0.37% vs 0.30%, NNH = 1429), invasive breast cancer (0.38% vs 0.30%, NNH = 1250), stroke (0.29% vs 0.21%, NNH = 1250), and venous thromboembolic disease (0.34% vs 0.16%, NNH = 556). Bone fractures were less prevalent in the HRT group (total annual fracture rate, 1.47% vs 1.91%, NNT = 228), as was colorectal cancer (0.10% vs 0.16%, NNT = 1667). All of these differences except thromboembolic disease lost statistical significance when adjusting for multiple comparisons, but subgroup analyses showed these differences in adverse events regardless of baseline risks of coronary heart disease and breast cancer. Individuals who adhered to the study medication showed greater differences in adverse events, and individuals who had already used HRT before the study had higher rates of breast cancer. Overall mortality was not different in the 2 groups. The excess risk of events in the global index was 19 per 10,000 person-years. In other words, an average of 1 additional adverse event would be expected over 5 years of treatment for every 100 women meeting these criteria.

ABSTRACT

BACKGROUND: One of the proposed benefits of postmenopausal hormone replacement therapy (HRT) is the prevention of coronary heart disease. This proposal is based on evidence from nonrandomized observational studies and intermediate outcomes such as improved lipid profiles. The possibility of harm from HRT has also been reported, particularly regarding breast cancer and thromboembolic disease. The Heart and Estrogen/progestin Replacement Study recently challenged the benefits of HRT, showing no overall protective effect on coronary heart disease (and an increased risk of harm in the first year of treatment) for women with prior coronary heart disease.

POPULATION STUDIED: The Women’s Health Initiative is a set of clinical trials with more than 160,000 women enrolled in studies of low-fat diet, calcium and vitamin D supplementation, and post-menopausal hormone use. This particular report focused on the trial of estrogen plus progestin in women with an intact uterus. A total of 16,608 post-menopausal women were randomized to receive either 1 daily tablet of conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg (Prempro) or placebo. Women were excluded if they had a history of breast cancer, other cancer within 10 years, hysterectomy, anemia, thrombocytopenia, alcoholism, or dementia. Ages ranged from 50 to 79 years (mean 63 years). Approximately 36% of the women were being treated for hypertension, 4.4% had diabetes, and 7.7% reported a history of cardiovascular disease.

STUDY DESIGN AND VALIDITY: This was a well-designed double-blind, randomized controlled trial with concealed allocation. Baseline characteristics were similar between groups. Follow-up was conducted 6 weeks after randomization, every 6 months with questionnaires, and annually with in-clinic visits. Intention-to-treat analysis was appropriate and would tend to find smaller differences between groups given the high dropout rates (42% in the HRT group and 38% in the placebo group). The trial was originally designed to last more than 8 years, but the independent safety monitoring board recommended stopping the trial when the difference in breast cancer rates exceeded a predetermined threshold and the global index was supportive of harm. When the trial was stopped in the spring of 2002, the average follow-up period was 5.2 years.

OUTCOMES MEASURED: The primary outcome measure was the rate of coronary heart disease, defined as acute myocardial infarction requiring overnight hospitalization, silent myocardial infarction determined from serial electrocardiograms, or coronary heart disease death. The secondary outcome measure was hip fracture rate. The primary adverse outcome measure was invasive breast cancer rate. Reported outcomes also included other cancers, total fractures, stroke, pulmonary embolism, deep vein thrombosis, and total mortality. A global index of outcomes was also calculated as a summary measure of risks and benefits. No measures of vasomotor symptoms or quality of life were reported.

RESULTS: Women in the HRT group had a higher annual incidence of coronary heart disease (0.37% vs 0.30%, NNH = 1429), invasive breast cancer (0.38% vs 0.30%, NNH = 1250), stroke (0.29% vs 0.21%, NNH = 1250), and venous thromboembolic disease (0.34% vs 0.16%, NNH = 556). Bone fractures were less prevalent in the HRT group (total annual fracture rate, 1.47% vs 1.91%, NNT = 228), as was colorectal cancer (0.10% vs 0.16%, NNT = 1667). All of these differences except thromboembolic disease lost statistical significance when adjusting for multiple comparisons, but subgroup analyses showed these differences in adverse events regardless of baseline risks of coronary heart disease and breast cancer. Individuals who adhered to the study medication showed greater differences in adverse events, and individuals who had already used HRT before the study had higher rates of breast cancer. Overall mortality was not different in the 2 groups. The excess risk of events in the global index was 19 per 10,000 person-years. In other words, an average of 1 additional adverse event would be expected over 5 years of treatment for every 100 women meeting these criteria.

ABSTRACT

BACKGROUND: One of the proposed benefits of postmenopausal hormone replacement therapy (HRT) is the prevention of coronary heart disease. This proposal is based on evidence from nonrandomized observational studies and intermediate outcomes such as improved lipid profiles. The possibility of harm from HRT has also been reported, particularly regarding breast cancer and thromboembolic disease. The Heart and Estrogen/progestin Replacement Study recently challenged the benefits of HRT, showing no overall protective effect on coronary heart disease (and an increased risk of harm in the first year of treatment) for women with prior coronary heart disease.

POPULATION STUDIED: The Women’s Health Initiative is a set of clinical trials with more than 160,000 women enrolled in studies of low-fat diet, calcium and vitamin D supplementation, and post-menopausal hormone use. This particular report focused on the trial of estrogen plus progestin in women with an intact uterus. A total of 16,608 post-menopausal women were randomized to receive either 1 daily tablet of conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg (Prempro) or placebo. Women were excluded if they had a history of breast cancer, other cancer within 10 years, hysterectomy, anemia, thrombocytopenia, alcoholism, or dementia. Ages ranged from 50 to 79 years (mean 63 years). Approximately 36% of the women were being treated for hypertension, 4.4% had diabetes, and 7.7% reported a history of cardiovascular disease.

STUDY DESIGN AND VALIDITY: This was a well-designed double-blind, randomized controlled trial with concealed allocation. Baseline characteristics were similar between groups. Follow-up was conducted 6 weeks after randomization, every 6 months with questionnaires, and annually with in-clinic visits. Intention-to-treat analysis was appropriate and would tend to find smaller differences between groups given the high dropout rates (42% in the HRT group and 38% in the placebo group). The trial was originally designed to last more than 8 years, but the independent safety monitoring board recommended stopping the trial when the difference in breast cancer rates exceeded a predetermined threshold and the global index was supportive of harm. When the trial was stopped in the spring of 2002, the average follow-up period was 5.2 years.

OUTCOMES MEASURED: The primary outcome measure was the rate of coronary heart disease, defined as acute myocardial infarction requiring overnight hospitalization, silent myocardial infarction determined from serial electrocardiograms, or coronary heart disease death. The secondary outcome measure was hip fracture rate. The primary adverse outcome measure was invasive breast cancer rate. Reported outcomes also included other cancers, total fractures, stroke, pulmonary embolism, deep vein thrombosis, and total mortality. A global index of outcomes was also calculated as a summary measure of risks and benefits. No measures of vasomotor symptoms or quality of life were reported.

RESULTS: Women in the HRT group had a higher annual incidence of coronary heart disease (0.37% vs 0.30%, NNH = 1429), invasive breast cancer (0.38% vs 0.30%, NNH = 1250), stroke (0.29% vs 0.21%, NNH = 1250), and venous thromboembolic disease (0.34% vs 0.16%, NNH = 556). Bone fractures were less prevalent in the HRT group (total annual fracture rate, 1.47% vs 1.91%, NNT = 228), as was colorectal cancer (0.10% vs 0.16%, NNT = 1667). All of these differences except thromboembolic disease lost statistical significance when adjusting for multiple comparisons, but subgroup analyses showed these differences in adverse events regardless of baseline risks of coronary heart disease and breast cancer. Individuals who adhered to the study medication showed greater differences in adverse events, and individuals who had already used HRT before the study had higher rates of breast cancer. Overall mortality was not different in the 2 groups. The excess risk of events in the global index was 19 per 10,000 person-years. In other words, an average of 1 additional adverse event would be expected over 5 years of treatment for every 100 women meeting these criteria.

ABSTRACT

BACKGROUND: Suturing scalp lacerations can be a painful, time-consuming procedure. It often requires shaving a portion of the scalp and subsequent suture removal. The search for a less invasive means of wound closure led the authors to develop the hair apposition technique. After cleaning the wound, and without anesthesia, about 4 to 5 strands of hair from each side of the laceration are twisted together once and a drop of tissue adhesive is placed on the twist to hold it in place. A series of twists are placed over the laceration to appose the wound. Patients are instructed not to wash their hair for 2 days. This study compared the hair apposition technique with standard suturing methods.

POPULATION STUDIED: This study was performed at emergency departments at 2 tertiary care centers in Singapore. The authors enrolled 189 patients who had linear, nonstellate scalp lacerations less than 10 cm in length. They did not include patients with severely contaminated wounds, arterial bleeding not controlled with 5 minutes of pressure, hair length less than 3 cm, and medically unstable patients.

STUDY DESIGN AND VALIDITY: This study was a randomized, controlled clinical trial. In a concealed fashion, 93 patients were randomized to suturing and 96 patients to the hair apposition technique. Both groups had their wounds irrigated and cleansed in a similar fashion. The control group was shaved according to local practice and received an injection of local anesthetic; young children sometimes received oral sedation. Hair washing was discouraged for 1 week in the suture group. No subject in the study group received anesthesia or sedation. A senior physician who was not involved in the initial treatment evaluated subjects after 1 week; sutures were removed at that time as well. If complications were noted, the patient was followed weekly for as long as 4 weeks.

OUTCOMES MEASURED: Primary outcome measures were wound healing and the presence of complications including infection, scarring, bleeding, wound breakdown, and allergy. Secondary outcome measures were duration of procedure, pain perception, and patient preference.

RESULTS: Overall, complications were reduced by the hair apposition technique (7.4% vs 21.5%; P = .005, NNT = 7). Most of the difference in complication rates can be attributed to the decreased scarring (at 1 week) found in the hair apposition technique group. Wound breakdown, bleeding, and infection rates were similar in both groups. The hair apposition technique was quicker than suturing (median time of 5 vs 15 minutes; P < .001). Less pain was reported in the hair apposition technique group (median score 2 vs 4 [out of 10 possible]); P < .001). In the hair apposition technique group, 84% claimed they would be willing to have the procedure in the future compared with only 10% in the suture group.

ABSTRACT

BACKGROUND: Suturing scalp lacerations can be a painful, time-consuming procedure. It often requires shaving a portion of the scalp and subsequent suture removal. The search for a less invasive means of wound closure led the authors to develop the hair apposition technique. After cleaning the wound, and without anesthesia, about 4 to 5 strands of hair from each side of the laceration are twisted together once and a drop of tissue adhesive is placed on the twist to hold it in place. A series of twists are placed over the laceration to appose the wound. Patients are instructed not to wash their hair for 2 days. This study compared the hair apposition technique with standard suturing methods.

POPULATION STUDIED: This study was performed at emergency departments at 2 tertiary care centers in Singapore. The authors enrolled 189 patients who had linear, nonstellate scalp lacerations less than 10 cm in length. They did not include patients with severely contaminated wounds, arterial bleeding not controlled with 5 minutes of pressure, hair length less than 3 cm, and medically unstable patients.

STUDY DESIGN AND VALIDITY: This study was a randomized, controlled clinical trial. In a concealed fashion, 93 patients were randomized to suturing and 96 patients to the hair apposition technique. Both groups had their wounds irrigated and cleansed in a similar fashion. The control group was shaved according to local practice and received an injection of local anesthetic; young children sometimes received oral sedation. Hair washing was discouraged for 1 week in the suture group. No subject in the study group received anesthesia or sedation. A senior physician who was not involved in the initial treatment evaluated subjects after 1 week; sutures were removed at that time as well. If complications were noted, the patient was followed weekly for as long as 4 weeks.

OUTCOMES MEASURED: Primary outcome measures were wound healing and the presence of complications including infection, scarring, bleeding, wound breakdown, and allergy. Secondary outcome measures were duration of procedure, pain perception, and patient preference.

RESULTS: Overall, complications were reduced by the hair apposition technique (7.4% vs 21.5%; P = .005, NNT = 7). Most of the difference in complication rates can be attributed to the decreased scarring (at 1 week) found in the hair apposition technique group. Wound breakdown, bleeding, and infection rates were similar in both groups. The hair apposition technique was quicker than suturing (median time of 5 vs 15 minutes; P < .001). Less pain was reported in the hair apposition technique group (median score 2 vs 4 [out of 10 possible]); P < .001). In the hair apposition technique group, 84% claimed they would be willing to have the procedure in the future compared with only 10% in the suture group.

ABSTRACT

BACKGROUND: Suturing scalp lacerations can be a painful, time-consuming procedure. It often requires shaving a portion of the scalp and subsequent suture removal. The search for a less invasive means of wound closure led the authors to develop the hair apposition technique. After cleaning the wound, and without anesthesia, about 4 to 5 strands of hair from each side of the laceration are twisted together once and a drop of tissue adhesive is placed on the twist to hold it in place. A series of twists are placed over the laceration to appose the wound. Patients are instructed not to wash their hair for 2 days. This study compared the hair apposition technique with standard suturing methods.

POPULATION STUDIED: This study was performed at emergency departments at 2 tertiary care centers in Singapore. The authors enrolled 189 patients who had linear, nonstellate scalp lacerations less than 10 cm in length. They did not include patients with severely contaminated wounds, arterial bleeding not controlled with 5 minutes of pressure, hair length less than 3 cm, and medically unstable patients.

STUDY DESIGN AND VALIDITY: This study was a randomized, controlled clinical trial. In a concealed fashion, 93 patients were randomized to suturing and 96 patients to the hair apposition technique. Both groups had their wounds irrigated and cleansed in a similar fashion. The control group was shaved according to local practice and received an injection of local anesthetic; young children sometimes received oral sedation. Hair washing was discouraged for 1 week in the suture group. No subject in the study group received anesthesia or sedation. A senior physician who was not involved in the initial treatment evaluated subjects after 1 week; sutures were removed at that time as well. If complications were noted, the patient was followed weekly for as long as 4 weeks.

OUTCOMES MEASURED: Primary outcome measures were wound healing and the presence of complications including infection, scarring, bleeding, wound breakdown, and allergy. Secondary outcome measures were duration of procedure, pain perception, and patient preference.

RESULTS: Overall, complications were reduced by the hair apposition technique (7.4% vs 21.5%; P = .005, NNT = 7). Most of the difference in complication rates can be attributed to the decreased scarring (at 1 week) found in the hair apposition technique group. Wound breakdown, bleeding, and infection rates were similar in both groups. The hair apposition technique was quicker than suturing (median time of 5 vs 15 minutes; P < .001). Less pain was reported in the hair apposition technique group (median score 2 vs 4 [out of 10 possible]); P < .001). In the hair apposition technique group, 84% claimed they would be willing to have the procedure in the future compared with only 10% in the suture group.