Q&A

BACKGROUND: Folate levels (routinely ordered for evaluation of macrocytosis with or without anemia) are poor predictors of true body stores, and low levels are only one of several causes of macrocytosis and anemia. Though better indicators of true body stores, erythrocyte folate levels may remain normal in early deficiency or may show false lows in chronic alcoholism, pregnancy, and cobalamin deficiency. Previous studies have led some to conclude that folate evaluations are ordered too often, and one report recommends empiric treatment with folic acid instead of folate testing for alcoholic patients with macrocytic anemia because of the low value of folate tests.

POPULATION STUDIED: The investigators evaluated the records of all patients who had a folate level drawn during hospitalization at 1 of 3 inpatient settings (an urban public teaching hospital, a private tertiary-care hospital, and a Department of Veterans Affairs [VA] teaching hospital) for a 1-year period (n=2998).

STUDY DESIGN AND VALIDITY: The study was a retrospective review of patient records that included a folate level determination. Several measures were recorded including total number of serum folate levels, the number of low serum folate levels (defined as from <1.5 ng/mL to <2.8 ng/mL among the 3 hospitals), erythrocyte folate levels (<95 ng/mL), anemia (hemoglobin <14 g/dL in men and <12g/dL in women), macrocytosis (mean corpuscular volume <99 fL), and microcytosis (mean corpuscular volume <80 fL). When the records revealed low folate levels, the medical records were reviewed to determine further patient characteristics and comorbid diagnoses. Reviewers determined if clinicians’ behavior was influenced by the low folate levels, including whether the low level was noted in a progress note or was an attempt made to determine cause and whether supplementation was given. A cost analysis was calculated using figures from 2 of the hospitals. Figures were not available from the VA hospital.Overall, the methods of this study were appropriate to answer the question. However, there are limitations with any retrospective study. For example, it is possible that clinicians took actions that were not documented in the medical record. Also, cost estimates may not be generalizable to private practice as they were taken from teaching hospitals where testing may be more prevalent.

OUTCOMES MEASURED: Reviewers determined the total number of low folate levels and clinical responses to those levels. Cost per abnormal test result was calculated and compared with the cost of empiric treatment with folic acid.

RESULTS: Only 68 of the 2998 (2.3%) folate measures were low. Low levels were recorded in 35 cases showing folate deficiency (53%); a possible cause was mentioned in 17 cases (24%); and folic acid was prescribed in only 16 cases (24%). Overall, the clinician response to folate level testing was less than 0.5%. This response rate results in a cost of $9979 spent on folate level determinations for each clinical response. In contrast, the cost of empiric treatment with folic acid would have been a maximum of $5.50 for a 90-day supply, totaling $6914 if all patients at the 2 hospitals included in the cost analysis had been treated (n=1257).

BACKGROUND: Folate levels (routinely ordered for evaluation of macrocytosis with or without anemia) are poor predictors of true body stores, and low levels are only one of several causes of macrocytosis and anemia. Though better indicators of true body stores, erythrocyte folate levels may remain normal in early deficiency or may show false lows in chronic alcoholism, pregnancy, and cobalamin deficiency. Previous studies have led some to conclude that folate evaluations are ordered too often, and one report recommends empiric treatment with folic acid instead of folate testing for alcoholic patients with macrocytic anemia because of the low value of folate tests.

POPULATION STUDIED: The investigators evaluated the records of all patients who had a folate level drawn during hospitalization at 1 of 3 inpatient settings (an urban public teaching hospital, a private tertiary-care hospital, and a Department of Veterans Affairs [VA] teaching hospital) for a 1-year period (n=2998).

STUDY DESIGN AND VALIDITY: The study was a retrospective review of patient records that included a folate level determination. Several measures were recorded including total number of serum folate levels, the number of low serum folate levels (defined as from <1.5 ng/mL to <2.8 ng/mL among the 3 hospitals), erythrocyte folate levels (<95 ng/mL), anemia (hemoglobin <14 g/dL in men and <12g/dL in women), macrocytosis (mean corpuscular volume <99 fL), and microcytosis (mean corpuscular volume <80 fL). When the records revealed low folate levels, the medical records were reviewed to determine further patient characteristics and comorbid diagnoses. Reviewers determined if clinicians’ behavior was influenced by the low folate levels, including whether the low level was noted in a progress note or was an attempt made to determine cause and whether supplementation was given. A cost analysis was calculated using figures from 2 of the hospitals. Figures were not available from the VA hospital.Overall, the methods of this study were appropriate to answer the question. However, there are limitations with any retrospective study. For example, it is possible that clinicians took actions that were not documented in the medical record. Also, cost estimates may not be generalizable to private practice as they were taken from teaching hospitals where testing may be more prevalent.

OUTCOMES MEASURED: Reviewers determined the total number of low folate levels and clinical responses to those levels. Cost per abnormal test result was calculated and compared with the cost of empiric treatment with folic acid.

RESULTS: Only 68 of the 2998 (2.3%) folate measures were low. Low levels were recorded in 35 cases showing folate deficiency (53%); a possible cause was mentioned in 17 cases (24%); and folic acid was prescribed in only 16 cases (24%). Overall, the clinician response to folate level testing was less than 0.5%. This response rate results in a cost of $9979 spent on folate level determinations for each clinical response. In contrast, the cost of empiric treatment with folic acid would have been a maximum of $5.50 for a 90-day supply, totaling $6914 if all patients at the 2 hospitals included in the cost analysis had been treated (n=1257).

BACKGROUND: Folate levels (routinely ordered for evaluation of macrocytosis with or without anemia) are poor predictors of true body stores, and low levels are only one of several causes of macrocytosis and anemia. Though better indicators of true body stores, erythrocyte folate levels may remain normal in early deficiency or may show false lows in chronic alcoholism, pregnancy, and cobalamin deficiency. Previous studies have led some to conclude that folate evaluations are ordered too often, and one report recommends empiric treatment with folic acid instead of folate testing for alcoholic patients with macrocytic anemia because of the low value of folate tests.

POPULATION STUDIED: The investigators evaluated the records of all patients who had a folate level drawn during hospitalization at 1 of 3 inpatient settings (an urban public teaching hospital, a private tertiary-care hospital, and a Department of Veterans Affairs [VA] teaching hospital) for a 1-year period (n=2998).

STUDY DESIGN AND VALIDITY: The study was a retrospective review of patient records that included a folate level determination. Several measures were recorded including total number of serum folate levels, the number of low serum folate levels (defined as from <1.5 ng/mL to <2.8 ng/mL among the 3 hospitals), erythrocyte folate levels (<95 ng/mL), anemia (hemoglobin <14 g/dL in men and <12g/dL in women), macrocytosis (mean corpuscular volume <99 fL), and microcytosis (mean corpuscular volume <80 fL). When the records revealed low folate levels, the medical records were reviewed to determine further patient characteristics and comorbid diagnoses. Reviewers determined if clinicians’ behavior was influenced by the low folate levels, including whether the low level was noted in a progress note or was an attempt made to determine cause and whether supplementation was given. A cost analysis was calculated using figures from 2 of the hospitals. Figures were not available from the VA hospital.Overall, the methods of this study were appropriate to answer the question. However, there are limitations with any retrospective study. For example, it is possible that clinicians took actions that were not documented in the medical record. Also, cost estimates may not be generalizable to private practice as they were taken from teaching hospitals where testing may be more prevalent.

OUTCOMES MEASURED: Reviewers determined the total number of low folate levels and clinical responses to those levels. Cost per abnormal test result was calculated and compared with the cost of empiric treatment with folic acid.

RESULTS: Only 68 of the 2998 (2.3%) folate measures were low. Low levels were recorded in 35 cases showing folate deficiency (53%); a possible cause was mentioned in 17 cases (24%); and folic acid was prescribed in only 16 cases (24%). Overall, the clinician response to folate level testing was less than 0.5%. This response rate results in a cost of $9979 spent on folate level determinations for each clinical response. In contrast, the cost of empiric treatment with folic acid would have been a maximum of $5.50 for a 90-day supply, totaling $6914 if all patients at the 2 hospitals included in the cost analysis had been treated (n=1257).

BACKGROUND: Current topical treatments of seborrheic dermatitis include steroids, selenium sulfide, pyrithione zinc, coal tar preparations, terbinafine, ketoconazole, and ultraviolet phototherapy. Topical steroids are often of limited use because of disease chronicity. Randomized controlled trials with bifonazole shampoo, ketoconazole cream, and lithium succinate ointment claim clinical efficacy.^1-4 Topical metronidazole has never been evaluated in the treatment of seborrheic dermatitis.

POPULATION STUDIED: The study participants were 44 adults (mean age=24 years; range: 19-40 years) clinically diagnosed with seborrheic dermatitis in a specialty setting. The patients were to have discontinued any other topical treatments at least 2 weeks before enrollment. The study took place in India, but the clinical setting was not further detailed.

STUDY DESIGN AND VALIDITY: The patients were randomly assigned by an undisclosed method (allocation concealment uncertain) to either the treatment (n=22) or placebo group (n=22). The treatment group applied 1% metronidazole gel to affected areas twice daily. The placebo group applied only the vehicle gel in an identical container with the same frequency. Six sites were evaluated (scalp, eyebrows, bridge of the nose, nasolabial folds, posterior ears, and chest) for signs and symptoms (erythema, scales, papules, and pruritus) at 2-week intervals for 8 weeks. A numerical grade (0=clear; 1=mild; 2=moderate; 3=severe) was given for each sign or symptom at each site and then totaled for an overall severity score. Patients were questioned regarding adverse effects and concomitant medication use at each visit. A global evaluation was made at the final visit. Patients were ascertained to have complete clearing, marked improvement, moderate improvement, or slight improvement. They were analyzed in their respective randomized groups; however, persons not completing the study were not included for analysis.

OUTCOMES MEASURED: The primary outcomes measured were seborrheic dermatitis severity scores and global evaluation of clinical improvement. The clinical tolerability of treatment versus placebo was also evaluated.

RESULTS: Twenty-one patients (95%) were included for analysis in the treatment group and 17 (77%) in the placebo group. Baseline severity scores and the distribution of seborrheic dermatitis were not found to be significantly different between treatment groups. One patient in the treatment group left for reasons unrelated to the study. Five patients in the placebo group left for lack of clinical improvement or worsening disease. At 8 weeks, the mean severity score between the treatment and placebo groups was 28.5 versus 7.9 (P <.001), respectively. The difference was statistically significant as early as 2 weeks. Fourteen patients in the treatment group versus 2 patients in the placebo group were noted to have marked improvement or complete clearing at the global evaluation (P <.0001; number needed to treat=2).

BACKGROUND: Current topical treatments of seborrheic dermatitis include steroids, selenium sulfide, pyrithione zinc, coal tar preparations, terbinafine, ketoconazole, and ultraviolet phototherapy. Topical steroids are often of limited use because of disease chronicity. Randomized controlled trials with bifonazole shampoo, ketoconazole cream, and lithium succinate ointment claim clinical efficacy.^1-4 Topical metronidazole has never been evaluated in the treatment of seborrheic dermatitis.

POPULATION STUDIED: The study participants were 44 adults (mean age=24 years; range: 19-40 years) clinically diagnosed with seborrheic dermatitis in a specialty setting. The patients were to have discontinued any other topical treatments at least 2 weeks before enrollment. The study took place in India, but the clinical setting was not further detailed.

STUDY DESIGN AND VALIDITY: The patients were randomly assigned by an undisclosed method (allocation concealment uncertain) to either the treatment (n=22) or placebo group (n=22). The treatment group applied 1% metronidazole gel to affected areas twice daily. The placebo group applied only the vehicle gel in an identical container with the same frequency. Six sites were evaluated (scalp, eyebrows, bridge of the nose, nasolabial folds, posterior ears, and chest) for signs and symptoms (erythema, scales, papules, and pruritus) at 2-week intervals for 8 weeks. A numerical grade (0=clear; 1=mild; 2=moderate; 3=severe) was given for each sign or symptom at each site and then totaled for an overall severity score. Patients were questioned regarding adverse effects and concomitant medication use at each visit. A global evaluation was made at the final visit. Patients were ascertained to have complete clearing, marked improvement, moderate improvement, or slight improvement. They were analyzed in their respective randomized groups; however, persons not completing the study were not included for analysis.

OUTCOMES MEASURED: The primary outcomes measured were seborrheic dermatitis severity scores and global evaluation of clinical improvement. The clinical tolerability of treatment versus placebo was also evaluated.

RESULTS: Twenty-one patients (95%) were included for analysis in the treatment group and 17 (77%) in the placebo group. Baseline severity scores and the distribution of seborrheic dermatitis were not found to be significantly different between treatment groups. One patient in the treatment group left for reasons unrelated to the study. Five patients in the placebo group left for lack of clinical improvement or worsening disease. At 8 weeks, the mean severity score between the treatment and placebo groups was 28.5 versus 7.9 (P <.001), respectively. The difference was statistically significant as early as 2 weeks. Fourteen patients in the treatment group versus 2 patients in the placebo group were noted to have marked improvement or complete clearing at the global evaluation (P <.0001; number needed to treat=2).

BACKGROUND: Current topical treatments of seborrheic dermatitis include steroids, selenium sulfide, pyrithione zinc, coal tar preparations, terbinafine, ketoconazole, and ultraviolet phototherapy. Topical steroids are often of limited use because of disease chronicity. Randomized controlled trials with bifonazole shampoo, ketoconazole cream, and lithium succinate ointment claim clinical efficacy.^1-4 Topical metronidazole has never been evaluated in the treatment of seborrheic dermatitis.

POPULATION STUDIED: The study participants were 44 adults (mean age=24 years; range: 19-40 years) clinically diagnosed with seborrheic dermatitis in a specialty setting. The patients were to have discontinued any other topical treatments at least 2 weeks before enrollment. The study took place in India, but the clinical setting was not further detailed.

STUDY DESIGN AND VALIDITY: The patients were randomly assigned by an undisclosed method (allocation concealment uncertain) to either the treatment (n=22) or placebo group (n=22). The treatment group applied 1% metronidazole gel to affected areas twice daily. The placebo group applied only the vehicle gel in an identical container with the same frequency. Six sites were evaluated (scalp, eyebrows, bridge of the nose, nasolabial folds, posterior ears, and chest) for signs and symptoms (erythema, scales, papules, and pruritus) at 2-week intervals for 8 weeks. A numerical grade (0=clear; 1=mild; 2=moderate; 3=severe) was given for each sign or symptom at each site and then totaled for an overall severity score. Patients were questioned regarding adverse effects and concomitant medication use at each visit. A global evaluation was made at the final visit. Patients were ascertained to have complete clearing, marked improvement, moderate improvement, or slight improvement. They were analyzed in their respective randomized groups; however, persons not completing the study were not included for analysis.

OUTCOMES MEASURED: The primary outcomes measured were seborrheic dermatitis severity scores and global evaluation of clinical improvement. The clinical tolerability of treatment versus placebo was also evaluated.

RESULTS: Twenty-one patients (95%) were included for analysis in the treatment group and 17 (77%) in the placebo group. Baseline severity scores and the distribution of seborrheic dermatitis were not found to be significantly different between treatment groups. One patient in the treatment group left for reasons unrelated to the study. Five patients in the placebo group left for lack of clinical improvement or worsening disease. At 8 weeks, the mean severity score between the treatment and placebo groups was 28.5 versus 7.9 (P <.001), respectively. The difference was statistically significant as early as 2 weeks. Fourteen patients in the treatment group versus 2 patients in the placebo group were noted to have marked improvement or complete clearing at the global evaluation (P <.0001; number needed to treat=2).

BACKGROUND: Dyspepsia (defined as pain or discomfort centered in the upper abdomen) is a common primary care problem, but optimal management is unclear. Nonulcer dyspepsia is the most common subtype, and controversy exists regarding the role of H pylori in this subtype. This systematic review assesses the efficacy of treatment for H pylori on symptoms of dyspepsia.

POPULATION STUDIED: The authors combined the results of 10 studies of therapy of 1747 patients with nonulcer dyspepsia and documented H pylori infection. The investigators included only randomized controlled trials lasting at least 1 month that used antibiotic or bismuth therapy that was effective against H pylori. No information was given on age, sex, body mass index, smoking, duration of symptoms, referral pattern, diagnostic workup, or comorbidity, making generalizability to the usual family practice setting difficult.

STUDY DESIGN AND VALIDITY: The literature search included MEDLINE (1984-1999, all languages, through 2 databases), gastroenterology meeting abstracts, reference lists from review and other articles, and consultation with manufacturers of H pylori medications, a working consensus panel, and other experts. Information on the study sample, intervention, study design, study duration, quality, and outcomes was obtained by 2 investigators independently; agreement was excellent (k=0.92) for methodologic quality, and differences were resolved by consensus. This systematic review was well done. Its strengths included the thorough search and the quality of the review process. A major weakness is the use of a symptom-based diagnostic category (nonulcer dyspepsia), which recent studies have suggested does not discriminate efficiently between specific diseases. When combined with the absence of information about the subjects, it is difficult to know what clinical population is being treated. Other weaknesses include the lack of information on studies for which only abstracts were found and the lack of assessment of the impact of age, obesity, duration of symptoms before treatment, and other factors that might affect the outcomes measured.

OUTCOMES MEASURED: The primary outcome was improvement of symptoms. A secondary analysis addressed eradication of H pylori and its relationship to symptomatic improvement. The article did not address other outcomes important in primary care of patients with dyspepsia, such as medication cost, medication side effects, or impact on function or quality of life.

RESULTS: Ten studies (7 published studies and 3 abstracts) were found, but only 7 provided information on treatment success at 1 month. The available data did not permit calculation of an effect size for symptoms. Formal testing for heterogeneity of effect was statistically significant (P=.04). The authors did not provide an explanation for this heterogeneity, calling into question the validity of aggregating the data. The absolute difference between treatment and control groups ranged from 5% in favor of the control group to 20% in favor of the treatment group, and only one trial achieved a statistically significant difference. A pooled odds ratio found no significant differences between treatment and control groups; sensitivity analysis addressing methodologic quality, precision of definition of dyspepsia, and duration of follow-up did not change this finding.

BACKGROUND: Dyspepsia (defined as pain or discomfort centered in the upper abdomen) is a common primary care problem, but optimal management is unclear. Nonulcer dyspepsia is the most common subtype, and controversy exists regarding the role of H pylori in this subtype. This systematic review assesses the efficacy of treatment for H pylori on symptoms of dyspepsia.

POPULATION STUDIED: The authors combined the results of 10 studies of therapy of 1747 patients with nonulcer dyspepsia and documented H pylori infection. The investigators included only randomized controlled trials lasting at least 1 month that used antibiotic or bismuth therapy that was effective against H pylori. No information was given on age, sex, body mass index, smoking, duration of symptoms, referral pattern, diagnostic workup, or comorbidity, making generalizability to the usual family practice setting difficult.

STUDY DESIGN AND VALIDITY: The literature search included MEDLINE (1984-1999, all languages, through 2 databases), gastroenterology meeting abstracts, reference lists from review and other articles, and consultation with manufacturers of H pylori medications, a working consensus panel, and other experts. Information on the study sample, intervention, study design, study duration, quality, and outcomes was obtained by 2 investigators independently; agreement was excellent (k=0.92) for methodologic quality, and differences were resolved by consensus. This systematic review was well done. Its strengths included the thorough search and the quality of the review process. A major weakness is the use of a symptom-based diagnostic category (nonulcer dyspepsia), which recent studies have suggested does not discriminate efficiently between specific diseases. When combined with the absence of information about the subjects, it is difficult to know what clinical population is being treated. Other weaknesses include the lack of information on studies for which only abstracts were found and the lack of assessment of the impact of age, obesity, duration of symptoms before treatment, and other factors that might affect the outcomes measured.

OUTCOMES MEASURED: The primary outcome was improvement of symptoms. A secondary analysis addressed eradication of H pylori and its relationship to symptomatic improvement. The article did not address other outcomes important in primary care of patients with dyspepsia, such as medication cost, medication side effects, or impact on function or quality of life.

RESULTS: Ten studies (7 published studies and 3 abstracts) were found, but only 7 provided information on treatment success at 1 month. The available data did not permit calculation of an effect size for symptoms. Formal testing for heterogeneity of effect was statistically significant (P=.04). The authors did not provide an explanation for this heterogeneity, calling into question the validity of aggregating the data. The absolute difference between treatment and control groups ranged from 5% in favor of the control group to 20% in favor of the treatment group, and only one trial achieved a statistically significant difference. A pooled odds ratio found no significant differences between treatment and control groups; sensitivity analysis addressing methodologic quality, precision of definition of dyspepsia, and duration of follow-up did not change this finding.

BACKGROUND: Dyspepsia (defined as pain or discomfort centered in the upper abdomen) is a common primary care problem, but optimal management is unclear. Nonulcer dyspepsia is the most common subtype, and controversy exists regarding the role of H pylori in this subtype. This systematic review assesses the efficacy of treatment for H pylori on symptoms of dyspepsia.

POPULATION STUDIED: The authors combined the results of 10 studies of therapy of 1747 patients with nonulcer dyspepsia and documented H pylori infection. The investigators included only randomized controlled trials lasting at least 1 month that used antibiotic or bismuth therapy that was effective against H pylori. No information was given on age, sex, body mass index, smoking, duration of symptoms, referral pattern, diagnostic workup, or comorbidity, making generalizability to the usual family practice setting difficult.

STUDY DESIGN AND VALIDITY: The literature search included MEDLINE (1984-1999, all languages, through 2 databases), gastroenterology meeting abstracts, reference lists from review and other articles, and consultation with manufacturers of H pylori medications, a working consensus panel, and other experts. Information on the study sample, intervention, study design, study duration, quality, and outcomes was obtained by 2 investigators independently; agreement was excellent (k=0.92) for methodologic quality, and differences were resolved by consensus. This systematic review was well done. Its strengths included the thorough search and the quality of the review process. A major weakness is the use of a symptom-based diagnostic category (nonulcer dyspepsia), which recent studies have suggested does not discriminate efficiently between specific diseases. When combined with the absence of information about the subjects, it is difficult to know what clinical population is being treated. Other weaknesses include the lack of information on studies for which only abstracts were found and the lack of assessment of the impact of age, obesity, duration of symptoms before treatment, and other factors that might affect the outcomes measured.

OUTCOMES MEASURED: The primary outcome was improvement of symptoms. A secondary analysis addressed eradication of H pylori and its relationship to symptomatic improvement. The article did not address other outcomes important in primary care of patients with dyspepsia, such as medication cost, medication side effects, or impact on function or quality of life.

RESULTS: Ten studies (7 published studies and 3 abstracts) were found, but only 7 provided information on treatment success at 1 month. The available data did not permit calculation of an effect size for symptoms. Formal testing for heterogeneity of effect was statistically significant (P=.04). The authors did not provide an explanation for this heterogeneity, calling into question the validity of aggregating the data. The absolute difference between treatment and control groups ranged from 5% in favor of the control group to 20% in favor of the treatment group, and only one trial achieved a statistically significant difference. A pooled odds ratio found no significant differences between treatment and control groups; sensitivity analysis addressing methodologic quality, precision of definition of dyspepsia, and duration of follow-up did not change this finding.

BACKGROUND: Several different ultrasonographic markers have been associated with Down syndrome. Although screening for fetal abnormalities associated with Down syndrome in the second trimester has become common, the accuracy of these markers is unknown.

POPULATION STUDIED: The meta-analysis included data on 130,365 unaffected fetuses and 1930 fetuses documented to have Down syndrome from 56 studies evaluating ultrasonographic markers for Down syndrome. These studies were published between January 1980 and February 1999. The mean maternal age was 34 years, and 88% of the studies looked at women with an increased risk of chromosomal abnormality.

STUDY DESIGN AND VALIDITY: The authors included English-language studies evaluating second-trimester ultrasound to detect Down syndrome (found by a MEDLINE search) and a review of bibliographies. Ninety-five percent of the studies used chromosomal analysis as the gold standard to assess for Down syndrome. Retrospective trials were included if the ultrasound interpretation and the diagnosis of Down syndrome were independently determined. Of 220 studies initially identified, 56 remained after poor-quality studies and studies without extractable data were excluded. The validity of the remaining studies was not explicitly described, although 2 reviewers independently evaluated them. The sensitivity and specificity for each marker were extracted and evaluated. Markers included choroid plexus cysts, nuchal fold thickening, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, femur shortening, and humerus shortening. Although the individual studies used different definitions of these markers, more than 90% of the data could be combined by using standard definitions in the meta-analysis. Publication bias was not addressed, but given the large numbers involved in the study, there would need to be a large number of unpublished studies to affect the results. Pooled sensitivity, specificity, and positive and negative predictive values and likelihood ratios were calculated using averages weighted for sample size. The authors evaluated positive and negative predictive values using 2 prevalences, first at 1:700 (the overall prevalence of Down syndrome) and again at 1:300 (the prevalence of Down syndrome in babies born to women older than 35 years).

OUTCOMES MEASURED: The authors classified each pregnancy into 1 of 3 outcomes: unaffected, Down syndrome, or any chromosomal abnormality. The outcome of all chromosomal abnormalities was used primarily for studies evaluating choroid plexus cysts, where 50% of the studies did not include data specifically for Down syndrome.

RESULTS: The overall prevalence of Down syndrome in the analysis was 1.5%, much higher than the 0.1% overall population risk. The sensitivity of each marker as an isolated abnormality was low (1%-16%), while the specificities were all greater than 95%. The most accurate test was a thickened nuchal fold, for which 2% of fetuses at average risk with this finding would have Down syndrome (the positive predictive value). This was the only test in patients at average risk for Down syndrome for which more cases would be identified than fetuses lost because of complications of the amniocentesis. Depending on the marker used, between 4454 and 87,413 average-risk women would have to be screened to detect 1 case of Down syndrome. For high-risk patients, between 1911 and 37,500 would be need to be screened. False-positives would range from 79 to 611, which means following most markers with an amniocentesis would result in more fetal loss than diagnoses of the disease. Because of the rarity of the disease, the absence of markers provides no significant reduction in the risk of having an infant with Down syndrome.

BACKGROUND: Several different ultrasonographic markers have been associated with Down syndrome. Although screening for fetal abnormalities associated with Down syndrome in the second trimester has become common, the accuracy of these markers is unknown.

POPULATION STUDIED: The meta-analysis included data on 130,365 unaffected fetuses and 1930 fetuses documented to have Down syndrome from 56 studies evaluating ultrasonographic markers for Down syndrome. These studies were published between January 1980 and February 1999. The mean maternal age was 34 years, and 88% of the studies looked at women with an increased risk of chromosomal abnormality.

STUDY DESIGN AND VALIDITY: The authors included English-language studies evaluating second-trimester ultrasound to detect Down syndrome (found by a MEDLINE search) and a review of bibliographies. Ninety-five percent of the studies used chromosomal analysis as the gold standard to assess for Down syndrome. Retrospective trials were included if the ultrasound interpretation and the diagnosis of Down syndrome were independently determined. Of 220 studies initially identified, 56 remained after poor-quality studies and studies without extractable data were excluded. The validity of the remaining studies was not explicitly described, although 2 reviewers independently evaluated them. The sensitivity and specificity for each marker were extracted and evaluated. Markers included choroid plexus cysts, nuchal fold thickening, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, femur shortening, and humerus shortening. Although the individual studies used different definitions of these markers, more than 90% of the data could be combined by using standard definitions in the meta-analysis. Publication bias was not addressed, but given the large numbers involved in the study, there would need to be a large number of unpublished studies to affect the results. Pooled sensitivity, specificity, and positive and negative predictive values and likelihood ratios were calculated using averages weighted for sample size. The authors evaluated positive and negative predictive values using 2 prevalences, first at 1:700 (the overall prevalence of Down syndrome) and again at 1:300 (the prevalence of Down syndrome in babies born to women older than 35 years).

OUTCOMES MEASURED: The authors classified each pregnancy into 1 of 3 outcomes: unaffected, Down syndrome, or any chromosomal abnormality. The outcome of all chromosomal abnormalities was used primarily for studies evaluating choroid plexus cysts, where 50% of the studies did not include data specifically for Down syndrome.

RESULTS: The overall prevalence of Down syndrome in the analysis was 1.5%, much higher than the 0.1% overall population risk. The sensitivity of each marker as an isolated abnormality was low (1%-16%), while the specificities were all greater than 95%. The most accurate test was a thickened nuchal fold, for which 2% of fetuses at average risk with this finding would have Down syndrome (the positive predictive value). This was the only test in patients at average risk for Down syndrome for which more cases would be identified than fetuses lost because of complications of the amniocentesis. Depending on the marker used, between 4454 and 87,413 average-risk women would have to be screened to detect 1 case of Down syndrome. For high-risk patients, between 1911 and 37,500 would be need to be screened. False-positives would range from 79 to 611, which means following most markers with an amniocentesis would result in more fetal loss than diagnoses of the disease. Because of the rarity of the disease, the absence of markers provides no significant reduction in the risk of having an infant with Down syndrome.

BACKGROUND: Several different ultrasonographic markers have been associated with Down syndrome. Although screening for fetal abnormalities associated with Down syndrome in the second trimester has become common, the accuracy of these markers is unknown.

POPULATION STUDIED: The meta-analysis included data on 130,365 unaffected fetuses and 1930 fetuses documented to have Down syndrome from 56 studies evaluating ultrasonographic markers for Down syndrome. These studies were published between January 1980 and February 1999. The mean maternal age was 34 years, and 88% of the studies looked at women with an increased risk of chromosomal abnormality.

STUDY DESIGN AND VALIDITY: The authors included English-language studies evaluating second-trimester ultrasound to detect Down syndrome (found by a MEDLINE search) and a review of bibliographies. Ninety-five percent of the studies used chromosomal analysis as the gold standard to assess for Down syndrome. Retrospective trials were included if the ultrasound interpretation and the diagnosis of Down syndrome were independently determined. Of 220 studies initially identified, 56 remained after poor-quality studies and studies without extractable data were excluded. The validity of the remaining studies was not explicitly described, although 2 reviewers independently evaluated them. The sensitivity and specificity for each marker were extracted and evaluated. Markers included choroid plexus cysts, nuchal fold thickening, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, femur shortening, and humerus shortening. Although the individual studies used different definitions of these markers, more than 90% of the data could be combined by using standard definitions in the meta-analysis. Publication bias was not addressed, but given the large numbers involved in the study, there would need to be a large number of unpublished studies to affect the results. Pooled sensitivity, specificity, and positive and negative predictive values and likelihood ratios were calculated using averages weighted for sample size. The authors evaluated positive and negative predictive values using 2 prevalences, first at 1:700 (the overall prevalence of Down syndrome) and again at 1:300 (the prevalence of Down syndrome in babies born to women older than 35 years).

OUTCOMES MEASURED: The authors classified each pregnancy into 1 of 3 outcomes: unaffected, Down syndrome, or any chromosomal abnormality. The outcome of all chromosomal abnormalities was used primarily for studies evaluating choroid plexus cysts, where 50% of the studies did not include data specifically for Down syndrome.

RESULTS: The overall prevalence of Down syndrome in the analysis was 1.5%, much higher than the 0.1% overall population risk. The sensitivity of each marker as an isolated abnormality was low (1%-16%), while the specificities were all greater than 95%. The most accurate test was a thickened nuchal fold, for which 2% of fetuses at average risk with this finding would have Down syndrome (the positive predictive value). This was the only test in patients at average risk for Down syndrome for which more cases would be identified than fetuses lost because of complications of the amniocentesis. Depending on the marker used, between 4454 and 87,413 average-risk women would have to be screened to detect 1 case of Down syndrome. For high-risk patients, between 1911 and 37,500 would be need to be screened. False-positives would range from 79 to 611, which means following most markers with an amniocentesis would result in more fetal loss than diagnoses of the disease. Because of the rarity of the disease, the absence of markers provides no significant reduction in the risk of having an infant with Down syndrome.

BACKGROUND: Antibiotic use is an important factor in the recent dramatic increase in antibiotic-resistant Streptococcus pneumoniae. Although most outpatient antibiotic prescriptions are for upper respiratory tract infections (URIs), systematic reviews have shown that these drugs have either a very modest benefit or no benefit in the treatment of common URIs. Because of the high rate of antibiotic use and growing resistance, the Centers for Disease Control and Prevention began a program to educate patients and physicians about the dangers of overuse. They first turned their attention to pediatric infections and then sponsored the development of guidelines for appropriate antibiotic use for URIs in adults. Numerous organizations, including the American Academy of Family Physicians (AAFP) and the American College of Physicians–American Society of Internal Medicine have endorsed these guidelines. This review will only cover the recommendations for acute sinusitis.

POPULATION STUDIED: These guidelines apply to nonhospitalized patients with acute sinusitis of a known or unknown etiology.

STUDY DESIGN AND VALIDITY: These are well-developed evidence-based practice guidelines for the appropriate use of antibiotics for acute sinusitis. When appropriate, the authors graded the evidence for the principles,¹ using a modification of the method proposed by Sackett and colleagues.² The authors addressed 3 specific questions (How is the diagnosis established? What is the likelihood that the symptoms are bacterial in origin? Is antibiotic therapy indicated?).² Although the specific search criteria are not given, the evidence for the reviews is based on Cochrane Collaboration and Agency for Healthcare Research and Quality systematic reviews. The authors updated the literature search for these reviews through March 2000. The recommendations were reviewed by experts in the field and several national organizations including the AAFP. The guidelines have not been subjected to testing.

OUTCOMES MEASURED: Patient-oriented outcomes for acute sinusitits (eg, resolution of symptoms at 14 days) were examined.

RESULTS: Sinus radiographs are not recommended for uncomplicated sinusitis (grade B evidence of no benefit). For patients with acute bacterial sinusitis (<2% of patients with a URI have a bacterial cause) and mild or moderate symptoms, antibiotics are not required (grade A evidence of no benefit). On the basis of the results of 3 meta-analyses, broader spectrum antibiotics offer no additional benefit. In patients with severe or persistent moderate symptoms, narrow spectrum antibiotics, such as amoxicillin, should be used.

BACKGROUND: Antibiotic use is an important factor in the recent dramatic increase in antibiotic-resistant Streptococcus pneumoniae. Although most outpatient antibiotic prescriptions are for upper respiratory tract infections (URIs), systematic reviews have shown that these drugs have either a very modest benefit or no benefit in the treatment of common URIs. Because of the high rate of antibiotic use and growing resistance, the Centers for Disease Control and Prevention began a program to educate patients and physicians about the dangers of overuse. They first turned their attention to pediatric infections and then sponsored the development of guidelines for appropriate antibiotic use for URIs in adults. Numerous organizations, including the American Academy of Family Physicians (AAFP) and the American College of Physicians–American Society of Internal Medicine have endorsed these guidelines. This review will only cover the recommendations for acute sinusitis.

POPULATION STUDIED: These guidelines apply to nonhospitalized patients with acute sinusitis of a known or unknown etiology.

STUDY DESIGN AND VALIDITY: These are well-developed evidence-based practice guidelines for the appropriate use of antibiotics for acute sinusitis. When appropriate, the authors graded the evidence for the principles,¹ using a modification of the method proposed by Sackett and colleagues.² The authors addressed 3 specific questions (How is the diagnosis established? What is the likelihood that the symptoms are bacterial in origin? Is antibiotic therapy indicated?).² Although the specific search criteria are not given, the evidence for the reviews is based on Cochrane Collaboration and Agency for Healthcare Research and Quality systematic reviews. The authors updated the literature search for these reviews through March 2000. The recommendations were reviewed by experts in the field and several national organizations including the AAFP. The guidelines have not been subjected to testing.

OUTCOMES MEASURED: Patient-oriented outcomes for acute sinusitits (eg, resolution of symptoms at 14 days) were examined.

RESULTS: Sinus radiographs are not recommended for uncomplicated sinusitis (grade B evidence of no benefit). For patients with acute bacterial sinusitis (<2% of patients with a URI have a bacterial cause) and mild or moderate symptoms, antibiotics are not required (grade A evidence of no benefit). On the basis of the results of 3 meta-analyses, broader spectrum antibiotics offer no additional benefit. In patients with severe or persistent moderate symptoms, narrow spectrum antibiotics, such as amoxicillin, should be used.

BACKGROUND: Antibiotic use is an important factor in the recent dramatic increase in antibiotic-resistant Streptococcus pneumoniae. Although most outpatient antibiotic prescriptions are for upper respiratory tract infections (URIs), systematic reviews have shown that these drugs have either a very modest benefit or no benefit in the treatment of common URIs. Because of the high rate of antibiotic use and growing resistance, the Centers for Disease Control and Prevention began a program to educate patients and physicians about the dangers of overuse. They first turned their attention to pediatric infections and then sponsored the development of guidelines for appropriate antibiotic use for URIs in adults. Numerous organizations, including the American Academy of Family Physicians (AAFP) and the American College of Physicians–American Society of Internal Medicine have endorsed these guidelines. This review will only cover the recommendations for acute sinusitis.

POPULATION STUDIED: These guidelines apply to nonhospitalized patients with acute sinusitis of a known or unknown etiology.

STUDY DESIGN AND VALIDITY: These are well-developed evidence-based practice guidelines for the appropriate use of antibiotics for acute sinusitis. When appropriate, the authors graded the evidence for the principles,¹ using a modification of the method proposed by Sackett and colleagues.² The authors addressed 3 specific questions (How is the diagnosis established? What is the likelihood that the symptoms are bacterial in origin? Is antibiotic therapy indicated?).² Although the specific search criteria are not given, the evidence for the reviews is based on Cochrane Collaboration and Agency for Healthcare Research and Quality systematic reviews. The authors updated the literature search for these reviews through March 2000. The recommendations were reviewed by experts in the field and several national organizations including the AAFP. The guidelines have not been subjected to testing.

OUTCOMES MEASURED: Patient-oriented outcomes for acute sinusitits (eg, resolution of symptoms at 14 days) were examined.

RESULTS: Sinus radiographs are not recommended for uncomplicated sinusitis (grade B evidence of no benefit). For patients with acute bacterial sinusitis (<2% of patients with a URI have a bacterial cause) and mild or moderate symptoms, antibiotics are not required (grade A evidence of no benefit). On the basis of the results of 3 meta-analyses, broader spectrum antibiotics offer no additional benefit. In patients with severe or persistent moderate symptoms, narrow spectrum antibiotics, such as amoxicillin, should be used.

BACKGROUND: Estrogen is known to affect the urethral mucosa and smooth muscle and has been part of the medical management of urinary incontinence in postmenopausal women. The clinical effectiveness of this therapy is controversial.

POPULATION STUDIED: Study participants included a total of 1525 postmenopausal women younger than 80 years with coronary heart disease who had not had a hysterectomy. All eligible women reported at least weekly urinary incontinence at the beginning of the study period.

STUDY DESIGN AND VALIDITY: The original Heart and Estrogen/progestin Replacement Study (HERS) enrolled 2763 postmenopausal women with established coronary heart disease to evaluate the role of hormone replacement therapy in the prevention of coronary heart disease. Of these women, 1525 participants reported at least weekly urinary incontinence and were included in this analysis. Patients were assigned by computer-generated random numbers to receive daily oral conjugated estrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg) in one tablet (Prempro; Wyeth Ayerst Research, Radnor, Pa) or identical placebo (concealed allocation assignment). Both participants and study personnel were blind to treatment status. Participants completed questionnaires concerning voiding habits and incontinence.

OUTCOMES MEASURED: The main outcome studied was the severity of incontinence, defined as the number of incontinent episodes per week. Outcomes were measured with a questionnaire conducted by blinded investigators at 4 months and then annually for 4 years.

RESULTS: Follow-up at 4 years was 98% complete in both the treatment and control groups. Urinary incontinence improved in 21% of the women taking hormones compared with 26% assigned to the placebo group, while 39% of the women in the hormone group reported worse incontinence compared with 27% of women in the placebo group (P=.001; number needed to harm=8). These results represented the mean of all follow-up visits and a significant difference was seen as early as 4 months. The actual number of incontinent episodes per week increased an average of 0.7 in the hormone group and decreased by 0.1 in the placebo group (P #060;.001).

BACKGROUND: Estrogen is known to affect the urethral mucosa and smooth muscle and has been part of the medical management of urinary incontinence in postmenopausal women. The clinical effectiveness of this therapy is controversial.

POPULATION STUDIED: Study participants included a total of 1525 postmenopausal women younger than 80 years with coronary heart disease who had not had a hysterectomy. All eligible women reported at least weekly urinary incontinence at the beginning of the study period.

STUDY DESIGN AND VALIDITY: The original Heart and Estrogen/progestin Replacement Study (HERS) enrolled 2763 postmenopausal women with established coronary heart disease to evaluate the role of hormone replacement therapy in the prevention of coronary heart disease. Of these women, 1525 participants reported at least weekly urinary incontinence and were included in this analysis. Patients were assigned by computer-generated random numbers to receive daily oral conjugated estrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg) in one tablet (Prempro; Wyeth Ayerst Research, Radnor, Pa) or identical placebo (concealed allocation assignment). Both participants and study personnel were blind to treatment status. Participants completed questionnaires concerning voiding habits and incontinence.

OUTCOMES MEASURED: The main outcome studied was the severity of incontinence, defined as the number of incontinent episodes per week. Outcomes were measured with a questionnaire conducted by blinded investigators at 4 months and then annually for 4 years.

RESULTS: Follow-up at 4 years was 98% complete in both the treatment and control groups. Urinary incontinence improved in 21% of the women taking hormones compared with 26% assigned to the placebo group, while 39% of the women in the hormone group reported worse incontinence compared with 27% of women in the placebo group (P=.001; number needed to harm=8). These results represented the mean of all follow-up visits and a significant difference was seen as early as 4 months. The actual number of incontinent episodes per week increased an average of 0.7 in the hormone group and decreased by 0.1 in the placebo group (P #060;.001).

BACKGROUND: Estrogen is known to affect the urethral mucosa and smooth muscle and has been part of the medical management of urinary incontinence in postmenopausal women. The clinical effectiveness of this therapy is controversial.

POPULATION STUDIED: Study participants included a total of 1525 postmenopausal women younger than 80 years with coronary heart disease who had not had a hysterectomy. All eligible women reported at least weekly urinary incontinence at the beginning of the study period.

STUDY DESIGN AND VALIDITY: The original Heart and Estrogen/progestin Replacement Study (HERS) enrolled 2763 postmenopausal women with established coronary heart disease to evaluate the role of hormone replacement therapy in the prevention of coronary heart disease. Of these women, 1525 participants reported at least weekly urinary incontinence and were included in this analysis. Patients were assigned by computer-generated random numbers to receive daily oral conjugated estrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg) in one tablet (Prempro; Wyeth Ayerst Research, Radnor, Pa) or identical placebo (concealed allocation assignment). Both participants and study personnel were blind to treatment status. Participants completed questionnaires concerning voiding habits and incontinence.

OUTCOMES MEASURED: The main outcome studied was the severity of incontinence, defined as the number of incontinent episodes per week. Outcomes were measured with a questionnaire conducted by blinded investigators at 4 months and then annually for 4 years.

RESULTS: Follow-up at 4 years was 98% complete in both the treatment and control groups. Urinary incontinence improved in 21% of the women taking hormones compared with 26% assigned to the placebo group, while 39% of the women in the hormone group reported worse incontinence compared with 27% of women in the placebo group (P=.001; number needed to harm=8). These results represented the mean of all follow-up visits and a significant difference was seen as early as 4 months. The actual number of incontinent episodes per week increased an average of 0.7 in the hormone group and decreased by 0.1 in the placebo group (P #060;.001).

BACKGROUND: Most patients who present with AOM receive antibiotics despite current controversy over whether antibiotics actually benefit patients. Health care providers have to balance concerns about antibiotic resistance with those regarding parental satisfaction.

POPULATION STUDIED: The study included 315 children aged 6 months to 10 years from general outpatient practices in southwest England who presented with acute ear pain with erythema, bulging, or perforation of the tympanic membrane on otoscopic examination. Children were excluded if they had pink tympanic membranes consistent with fever or crying alone, a history and examination consistent with otitis media with effusion and chronic suppurative otitis media, serious chronic disease, antibiotic use within the previous 2 weeks, previous complications of AOM, or if they appeared toxic.

STUDY DESIGN AND VALIDITY: This was a nonblinded controlled clinical trial with patients randomized to receive either immediate antibiotics (a prescription to be filled following the visit) or delayed antibiotics (instructions to return to clinic to pick up an prescription left at the reception desk in 3 days if the child was worse or not improving). When a patient was diagnosed with AOM, the physician opened an opaque envelope containing an advice sheet that allocated the patient to 1 of the 2 study groups. The advice sheet provided information on the benefits of the intervention, which the physician shared with the patient and parent to support the placebo effect of either intervention. The authors appropriately accounted for all study participants and used an intention-to-treat analysis.

OUTCOMES MEASURED: The authors measured duration and degree of pain, number of episodes of distress, amount of acetaminophen used, number of school days missed, and parental satisfaction scores as reported by parents in a daily diary.

RESULTS: Of 384 children eligible for the study, 315 were randomized, and 285 completed the study. A total of 132 of the 135 patients allocated to receive immediate antibiotics actually used them; 36 of the 150 children (24%) allocated to delayed prescription used antibiotics. Symptoms resolved in both groups in an average of 3 days. The children who received immediate antibiotics had significantly fewer days of earache (mean difference = -1.10 days; 95% confidence interval [CI], -0.54 to -1.48) and used fewer teaspoons of acetaminophen (mean difference = -0.52 tsp; 95% CI, -0.79 to -0.26). There was no difference between the 2 groups in mean pain scores, number of episodes of distress, or absence from school. Any effect of antibiotics seemed to occur only after the first 24 hours of illness. Diarrhea occurred in 19% of children who received antibiotics immediately, compared with 9% in the delayed group. Ninety-one percent of the parents in the immediate antibiotics group and 77% of those in the delayed antibiotics group were very satisfied with the treatment approach. Eighty-three percent of the parents whose children received antibiotics immediately believed that they would need to see the physician for future episodes, compared with 63% in the delayed antibiotics group; 76% versus 46% of parents in the immediate and delayed antibiotic groups, respectively, believed that antibiotics were very effective for AOM.

BACKGROUND: Most patients who present with AOM receive antibiotics despite current controversy over whether antibiotics actually benefit patients. Health care providers have to balance concerns about antibiotic resistance with those regarding parental satisfaction.

POPULATION STUDIED: The study included 315 children aged 6 months to 10 years from general outpatient practices in southwest England who presented with acute ear pain with erythema, bulging, or perforation of the tympanic membrane on otoscopic examination. Children were excluded if they had pink tympanic membranes consistent with fever or crying alone, a history and examination consistent with otitis media with effusion and chronic suppurative otitis media, serious chronic disease, antibiotic use within the previous 2 weeks, previous complications of AOM, or if they appeared toxic.

STUDY DESIGN AND VALIDITY: This was a nonblinded controlled clinical trial with patients randomized to receive either immediate antibiotics (a prescription to be filled following the visit) or delayed antibiotics (instructions to return to clinic to pick up an prescription left at the reception desk in 3 days if the child was worse or not improving). When a patient was diagnosed with AOM, the physician opened an opaque envelope containing an advice sheet that allocated the patient to 1 of the 2 study groups. The advice sheet provided information on the benefits of the intervention, which the physician shared with the patient and parent to support the placebo effect of either intervention. The authors appropriately accounted for all study participants and used an intention-to-treat analysis.

OUTCOMES MEASURED: The authors measured duration and degree of pain, number of episodes of distress, amount of acetaminophen used, number of school days missed, and parental satisfaction scores as reported by parents in a daily diary.

RESULTS: Of 384 children eligible for the study, 315 were randomized, and 285 completed the study. A total of 132 of the 135 patients allocated to receive immediate antibiotics actually used them; 36 of the 150 children (24%) allocated to delayed prescription used antibiotics. Symptoms resolved in both groups in an average of 3 days. The children who received immediate antibiotics had significantly fewer days of earache (mean difference = -1.10 days; 95% confidence interval [CI], -0.54 to -1.48) and used fewer teaspoons of acetaminophen (mean difference = -0.52 tsp; 95% CI, -0.79 to -0.26). There was no difference between the 2 groups in mean pain scores, number of episodes of distress, or absence from school. Any effect of antibiotics seemed to occur only after the first 24 hours of illness. Diarrhea occurred in 19% of children who received antibiotics immediately, compared with 9% in the delayed group. Ninety-one percent of the parents in the immediate antibiotics group and 77% of those in the delayed antibiotics group were very satisfied with the treatment approach. Eighty-three percent of the parents whose children received antibiotics immediately believed that they would need to see the physician for future episodes, compared with 63% in the delayed antibiotics group; 76% versus 46% of parents in the immediate and delayed antibiotic groups, respectively, believed that antibiotics were very effective for AOM.

BACKGROUND: Most patients who present with AOM receive antibiotics despite current controversy over whether antibiotics actually benefit patients. Health care providers have to balance concerns about antibiotic resistance with those regarding parental satisfaction.

POPULATION STUDIED: The study included 315 children aged 6 months to 10 years from general outpatient practices in southwest England who presented with acute ear pain with erythema, bulging, or perforation of the tympanic membrane on otoscopic examination. Children were excluded if they had pink tympanic membranes consistent with fever or crying alone, a history and examination consistent with otitis media with effusion and chronic suppurative otitis media, serious chronic disease, antibiotic use within the previous 2 weeks, previous complications of AOM, or if they appeared toxic.

STUDY DESIGN AND VALIDITY: This was a nonblinded controlled clinical trial with patients randomized to receive either immediate antibiotics (a prescription to be filled following the visit) or delayed antibiotics (instructions to return to clinic to pick up an prescription left at the reception desk in 3 days if the child was worse or not improving). When a patient was diagnosed with AOM, the physician opened an opaque envelope containing an advice sheet that allocated the patient to 1 of the 2 study groups. The advice sheet provided information on the benefits of the intervention, which the physician shared with the patient and parent to support the placebo effect of either intervention. The authors appropriately accounted for all study participants and used an intention-to-treat analysis.

OUTCOMES MEASURED: The authors measured duration and degree of pain, number of episodes of distress, amount of acetaminophen used, number of school days missed, and parental satisfaction scores as reported by parents in a daily diary.

RESULTS: Of 384 children eligible for the study, 315 were randomized, and 285 completed the study. A total of 132 of the 135 patients allocated to receive immediate antibiotics actually used them; 36 of the 150 children (24%) allocated to delayed prescription used antibiotics. Symptoms resolved in both groups in an average of 3 days. The children who received immediate antibiotics had significantly fewer days of earache (mean difference = -1.10 days; 95% confidence interval [CI], -0.54 to -1.48) and used fewer teaspoons of acetaminophen (mean difference = -0.52 tsp; 95% CI, -0.79 to -0.26). There was no difference between the 2 groups in mean pain scores, number of episodes of distress, or absence from school. Any effect of antibiotics seemed to occur only after the first 24 hours of illness. Diarrhea occurred in 19% of children who received antibiotics immediately, compared with 9% in the delayed group. Ninety-one percent of the parents in the immediate antibiotics group and 77% of those in the delayed antibiotics group were very satisfied with the treatment approach. Eighty-three percent of the parents whose children received antibiotics immediately believed that they would need to see the physician for future episodes, compared with 63% in the delayed antibiotics group; 76% versus 46% of parents in the immediate and delayed antibiotic groups, respectively, believed that antibiotics were very effective for AOM.

BACKGROUND: The increased platelet and endothelial thromboxane activity found in patients with preeclampsia can be inhibited by antiplatelet agents such as aspirin. This systematic review tested the hypothesis that antiplatelet drugs can prevent preeclampsia and its complications. Because of a theoretical risk of placental abruption, providers may currently be reluctant to prescribe aspirin in pregnancy.

POPULATION STUDIED: A total of 39 trials enrolling 30,563 women at risk for preeclampsia were identified. Participants were divided into prespecified subgroups: high or moderate risk for developing preeclampsia, before or after 20 weeks’ gestation at randomization, the dose of aspirin less than or equal to 75 mg, and the use of a placebo for the control group. High risk was defined as a history of previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease. Moderate risk was defined as primigravada, mild hypertension and no proteinurea, positve rollover test, abnormal uterine artery Doppler scan, multiple pregnancies, a family history of severe preeclampsia, and being a teenager. Most studies used aspirin versus placebo, and a minority of trials used other agents that included dipyridamole, heparin, or ozagrel.

STUDY DESIGN AND VALIDITY: The reviewers searched the Register of Trials maintained by the Cochrane Pregnancy and Childbirth Group, the Cochrane Controlled Trials Register, EMBASE, and the proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. Two pairs of reviewers assessed validity independently. Trials were excluded for quasirandomization, such as alternate allocation and if greater than 20% of participants were lost to follow-up or were not reported in the final results.

OUTCOMES MEASURED: The primary outcomes measured were preeclampsia, preterm birth, fetal or neonatal death and small for gestational age. Other outcomes included eclampsia, maternal death, placental abruption, and cesarean delivery.

RESULTS: The use of antiplatelet drugs was associated with a 15% reduction in the risk of preeclampsia (relative risk [RR]=0.85; 95% confidence interval [CI], 0.78-0.92; number needed to treat [NNT]=100). This 15% reduction was consistent across all subgroups except for women receiving more than 75 mg of aspirin (RR=0.35; 95% CI, 0.24-0.52). There was an 8% reduction in the risk of preterm birth (RR=0.92; 95% CI, 0.88-0.97; NNT=72) that was consistent across all subgroups except those receiving more than 75 mg of aspirin (RR=0.58; 95% CI, 0.38-0.88). There was a 14% reduction in the risk of fetal or neonatal death (RR=0.86; 95% CI, 0.75-0.98; NNT=250). There were no significant differences between treatment and control groups in all other outcomes measured, including the risk of placental abruption (RR=1.05; 95% CI, 0.83-1.32).

BACKGROUND: The increased platelet and endothelial thromboxane activity found in patients with preeclampsia can be inhibited by antiplatelet agents such as aspirin. This systematic review tested the hypothesis that antiplatelet drugs can prevent preeclampsia and its complications. Because of a theoretical risk of placental abruption, providers may currently be reluctant to prescribe aspirin in pregnancy.

POPULATION STUDIED: A total of 39 trials enrolling 30,563 women at risk for preeclampsia were identified. Participants were divided into prespecified subgroups: high or moderate risk for developing preeclampsia, before or after 20 weeks’ gestation at randomization, the dose of aspirin less than or equal to 75 mg, and the use of a placebo for the control group. High risk was defined as a history of previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease. Moderate risk was defined as primigravada, mild hypertension and no proteinurea, positve rollover test, abnormal uterine artery Doppler scan, multiple pregnancies, a family history of severe preeclampsia, and being a teenager. Most studies used aspirin versus placebo, and a minority of trials used other agents that included dipyridamole, heparin, or ozagrel.

STUDY DESIGN AND VALIDITY: The reviewers searched the Register of Trials maintained by the Cochrane Pregnancy and Childbirth Group, the Cochrane Controlled Trials Register, EMBASE, and the proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. Two pairs of reviewers assessed validity independently. Trials were excluded for quasirandomization, such as alternate allocation and if greater than 20% of participants were lost to follow-up or were not reported in the final results.

OUTCOMES MEASURED: The primary outcomes measured were preeclampsia, preterm birth, fetal or neonatal death and small for gestational age. Other outcomes included eclampsia, maternal death, placental abruption, and cesarean delivery.

RESULTS: The use of antiplatelet drugs was associated with a 15% reduction in the risk of preeclampsia (relative risk [RR]=0.85; 95% confidence interval [CI], 0.78-0.92; number needed to treat [NNT]=100). This 15% reduction was consistent across all subgroups except for women receiving more than 75 mg of aspirin (RR=0.35; 95% CI, 0.24-0.52). There was an 8% reduction in the risk of preterm birth (RR=0.92; 95% CI, 0.88-0.97; NNT=72) that was consistent across all subgroups except those receiving more than 75 mg of aspirin (RR=0.58; 95% CI, 0.38-0.88). There was a 14% reduction in the risk of fetal or neonatal death (RR=0.86; 95% CI, 0.75-0.98; NNT=250). There were no significant differences between treatment and control groups in all other outcomes measured, including the risk of placental abruption (RR=1.05; 95% CI, 0.83-1.32).

BACKGROUND: The increased platelet and endothelial thromboxane activity found in patients with preeclampsia can be inhibited by antiplatelet agents such as aspirin. This systematic review tested the hypothesis that antiplatelet drugs can prevent preeclampsia and its complications. Because of a theoretical risk of placental abruption, providers may currently be reluctant to prescribe aspirin in pregnancy.

POPULATION STUDIED: A total of 39 trials enrolling 30,563 women at risk for preeclampsia were identified. Participants were divided into prespecified subgroups: high or moderate risk for developing preeclampsia, before or after 20 weeks’ gestation at randomization, the dose of aspirin less than or equal to 75 mg, and the use of a placebo for the control group. High risk was defined as a history of previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease. Moderate risk was defined as primigravada, mild hypertension and no proteinurea, positve rollover test, abnormal uterine artery Doppler scan, multiple pregnancies, a family history of severe preeclampsia, and being a teenager. Most studies used aspirin versus placebo, and a minority of trials used other agents that included dipyridamole, heparin, or ozagrel.

STUDY DESIGN AND VALIDITY: The reviewers searched the Register of Trials maintained by the Cochrane Pregnancy and Childbirth Group, the Cochrane Controlled Trials Register, EMBASE, and the proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. Two pairs of reviewers assessed validity independently. Trials were excluded for quasirandomization, such as alternate allocation and if greater than 20% of participants were lost to follow-up or were not reported in the final results.

OUTCOMES MEASURED: The primary outcomes measured were preeclampsia, preterm birth, fetal or neonatal death and small for gestational age. Other outcomes included eclampsia, maternal death, placental abruption, and cesarean delivery.

RESULTS: The use of antiplatelet drugs was associated with a 15% reduction in the risk of preeclampsia (relative risk [RR]=0.85; 95% confidence interval [CI], 0.78-0.92; number needed to treat [NNT]=100). This 15% reduction was consistent across all subgroups except for women receiving more than 75 mg of aspirin (RR=0.35; 95% CI, 0.24-0.52). There was an 8% reduction in the risk of preterm birth (RR=0.92; 95% CI, 0.88-0.97; NNT=72) that was consistent across all subgroups except those receiving more than 75 mg of aspirin (RR=0.58; 95% CI, 0.38-0.88). There was a 14% reduction in the risk of fetal or neonatal death (RR=0.86; 95% CI, 0.75-0.98; NNT=250). There were no significant differences between treatment and control groups in all other outcomes measured, including the risk of placental abruption (RR=1.05; 95% CI, 0.83-1.32).

BACKGROUND: The safety of NSAIDs is not well documented, even through they are often used during pregnancy. The authors of this study estimated the risk of adverse pregnancy outcomes by examining NSAID prescription use in a large population of Danish women.

POPULATION STUDIED: The researchers assembled 2 separate study groups drawn from one county in Denmark. In one group 1462 pregnant women who had filled prescriptions for NSAIDs were compared with 17,259 controls to assess unfavorable birth outcomes. Those who had filled NSAID prescriptions anywhere from 30 days before conception up to the date of delivery were included. In the other group 4268 women who had first miscarriages were compared with 29,750 primiparous women with live births as controls. Patient information for both study groups was identified using a prescription registry, the Danish birth registry, and the county’s hospital discharge registry.

STUDY DESIGN AND VALIDITY: The incidence of adverse birth outcomes was assessed through a retrospective cohort design. The risk of miscarriage was determined by a case-control study. Information was collected for each subject on the number of NSAID prescriptions filled (specifically ibuprofen 400 or 600 mg), maternal age, smoking status, gravity, parity, gestational age at delivery, and size of the neonate. A subset of prescription data was verified by examining physician and hospital records.

OUTCOMES MEASURED: Primary outcomes included congenital abnormality (type not specified), low birth weight (less than 2500 g), preterm birth (<37 weeks’ gestation), and miscarriage.

RESULTS: Congenital abnormality, low birth weight, and preterm birth incidence were not higher in offspring of women who had taken a NSAID during pregnancy. Miscarriages were significantly higher in women who had filled a prescription for an NSAID the week before miscarriage (odds ratio=6.99; 95% confidence interval, 2.75-17.74). Miscarriage was not associated with prescriptions filled 10 to 12 weeks before the date of miscarriage.

BACKGROUND: The safety of NSAIDs is not well documented, even through they are often used during pregnancy. The authors of this study estimated the risk of adverse pregnancy outcomes by examining NSAID prescription use in a large population of Danish women.

POPULATION STUDIED: The researchers assembled 2 separate study groups drawn from one county in Denmark. In one group 1462 pregnant women who had filled prescriptions for NSAIDs were compared with 17,259 controls to assess unfavorable birth outcomes. Those who had filled NSAID prescriptions anywhere from 30 days before conception up to the date of delivery were included. In the other group 4268 women who had first miscarriages were compared with 29,750 primiparous women with live births as controls. Patient information for both study groups was identified using a prescription registry, the Danish birth registry, and the county’s hospital discharge registry.

STUDY DESIGN AND VALIDITY: The incidence of adverse birth outcomes was assessed through a retrospective cohort design. The risk of miscarriage was determined by a case-control study. Information was collected for each subject on the number of NSAID prescriptions filled (specifically ibuprofen 400 or 600 mg), maternal age, smoking status, gravity, parity, gestational age at delivery, and size of the neonate. A subset of prescription data was verified by examining physician and hospital records.

OUTCOMES MEASURED: Primary outcomes included congenital abnormality (type not specified), low birth weight (less than 2500 g), preterm birth (<37 weeks’ gestation), and miscarriage.

RESULTS: Congenital abnormality, low birth weight, and preterm birth incidence were not higher in offspring of women who had taken a NSAID during pregnancy. Miscarriages were significantly higher in women who had filled a prescription for an NSAID the week before miscarriage (odds ratio=6.99; 95% confidence interval, 2.75-17.74). Miscarriage was not associated with prescriptions filled 10 to 12 weeks before the date of miscarriage.

BACKGROUND: The safety of NSAIDs is not well documented, even through they are often used during pregnancy. The authors of this study estimated the risk of adverse pregnancy outcomes by examining NSAID prescription use in a large population of Danish women.

POPULATION STUDIED: The researchers assembled 2 separate study groups drawn from one county in Denmark. In one group 1462 pregnant women who had filled prescriptions for NSAIDs were compared with 17,259 controls to assess unfavorable birth outcomes. Those who had filled NSAID prescriptions anywhere from 30 days before conception up to the date of delivery were included. In the other group 4268 women who had first miscarriages were compared with 29,750 primiparous women with live births as controls. Patient information for both study groups was identified using a prescription registry, the Danish birth registry, and the county’s hospital discharge registry.

STUDY DESIGN AND VALIDITY: The incidence of adverse birth outcomes was assessed through a retrospective cohort design. The risk of miscarriage was determined by a case-control study. Information was collected for each subject on the number of NSAID prescriptions filled (specifically ibuprofen 400 or 600 mg), maternal age, smoking status, gravity, parity, gestational age at delivery, and size of the neonate. A subset of prescription data was verified by examining physician and hospital records.

OUTCOMES MEASURED: Primary outcomes included congenital abnormality (type not specified), low birth weight (less than 2500 g), preterm birth (<37 weeks’ gestation), and miscarriage.

RESULTS: Congenital abnormality, low birth weight, and preterm birth incidence were not higher in offspring of women who had taken a NSAID during pregnancy. Miscarriages were significantly higher in women who had filled a prescription for an NSAID the week before miscarriage (odds ratio=6.99; 95% confidence interval, 2.75-17.74). Miscarriage was not associated with prescriptions filled 10 to 12 weeks before the date of miscarriage.

BACKGROUND: Several studies have shown that initial treatment with subcutaneous low-molecular-weight heparin is as effective as intravenous unfractionated heparin in preventing the sequelae of VTE. This randomized controlled trial addressed this issue with a large population that included patients with pulmonary embolus (PE).

POPULATION STUDIED: A total of 900 patients from 74 hospitals in 16 countries were enrolled. Subjects were adults with venogram- or ultrasound-proven lower extremity deep venous thrombosis, symptomatic PE with high-probability ventilation-perfusion (V/Q) scan, or a positive angiogram with radiologic evidence of a lower extremity VTE. Exclusion criteria included previous administration of heparin or warfarin for more than 24 hours, risk for hemorrhage, and allergies to the medications or to pork products. The average age was 61 years; 55% were men. Twenty-four percent had had a previous VTE; 16% had cancer; and 32% had a concurrent PE. The study population seems to be similar to that of a family physician., although more information about referral pattern and local diagnostic and therapeutic protocols would be valuable.

STUDY DESIGN AND VALIDITY: This was a randomized unblinded trial. Subjects received 1 of 3 antithrombotic regimens: heparin bolus and continuous infusion to achieve a target activated partial thromboplastin time of 55 to 80 seconds, enoxaparin 1 mg per kg twice daily, or enoxaparin 1.5 mg per kg once daily. These regimens were continued for at least 5 days. Warfarin was started within the first 3 days and was continued for at least 3 months, adjusted to maintain an international normalized ratio between 2.0 and 3.0. All subjects received baseline V/Q scans or angiograms. Although the clinicians were not masked to treatment status, all imaging studies and outcomes were reviewed by committees masked to treatment status. The maker of enoxaparin sponsored and performed the study.

OUTCOMES MEASURED: The major outcomes were recurrence or worsening of VTE or PE, major hemorrhage (ie, >2.0 g/L hemoglobin drop, requiring transfusion of 2 or more units, bleeding requiring intervention, or death), thrombocytopenia, or other side effects. Cost and patient satisfaction were not addressed.

RESULTS: The groups were similar at baseline. There was no significant difference in recurrence or worsening of VTE among patients in the unfractionated heparin group (4.1%), enoxaparin daily group (4.4%), and enoxaparin twice-daily group (2.9%). New PE was rare in all 3 groups (4/900). Regardless of treatment, patients with cancer or symptomatic PE at baseline were at higher risk of subsequent VTE (odds ratio [OR]=3.7; 95% confidence interval [CI], 1.3-11; OR=3.4; 95% CI, 1.55-7.3), respectively. These findings were unchanged when analysis was restricted to subjects for whom all data were available. Similarly, there was no significant difference among the groups in the incidence of major hemorrhage (2.1%, 1.7%, 1.3%, respectively), death (3.1%, 3.7%, 2.2%, respectively), or thrombocytopenia. Adherence to enoxaparin in both groups was better than for unfractionated heparin group (83.6% and 85.3% vs 75.9%, respectively).

BACKGROUND: Several studies have shown that initial treatment with subcutaneous low-molecular-weight heparin is as effective as intravenous unfractionated heparin in preventing the sequelae of VTE. This randomized controlled trial addressed this issue with a large population that included patients with pulmonary embolus (PE).

POPULATION STUDIED: A total of 900 patients from 74 hospitals in 16 countries were enrolled. Subjects were adults with venogram- or ultrasound-proven lower extremity deep venous thrombosis, symptomatic PE with high-probability ventilation-perfusion (V/Q) scan, or a positive angiogram with radiologic evidence of a lower extremity VTE. Exclusion criteria included previous administration of heparin or warfarin for more than 24 hours, risk for hemorrhage, and allergies to the medications or to pork products. The average age was 61 years; 55% were men. Twenty-four percent had had a previous VTE; 16% had cancer; and 32% had a concurrent PE. The study population seems to be similar to that of a family physician., although more information about referral pattern and local diagnostic and therapeutic protocols would be valuable.

STUDY DESIGN AND VALIDITY: This was a randomized unblinded trial. Subjects received 1 of 3 antithrombotic regimens: heparin bolus and continuous infusion to achieve a target activated partial thromboplastin time of 55 to 80 seconds, enoxaparin 1 mg per kg twice daily, or enoxaparin 1.5 mg per kg once daily. These regimens were continued for at least 5 days. Warfarin was started within the first 3 days and was continued for at least 3 months, adjusted to maintain an international normalized ratio between 2.0 and 3.0. All subjects received baseline V/Q scans or angiograms. Although the clinicians were not masked to treatment status, all imaging studies and outcomes were reviewed by committees masked to treatment status. The maker of enoxaparin sponsored and performed the study.

OUTCOMES MEASURED: The major outcomes were recurrence or worsening of VTE or PE, major hemorrhage (ie, >2.0 g/L hemoglobin drop, requiring transfusion of 2 or more units, bleeding requiring intervention, or death), thrombocytopenia, or other side effects. Cost and patient satisfaction were not addressed.

RESULTS: The groups were similar at baseline. There was no significant difference in recurrence or worsening of VTE among patients in the unfractionated heparin group (4.1%), enoxaparin daily group (4.4%), and enoxaparin twice-daily group (2.9%). New PE was rare in all 3 groups (4/900). Regardless of treatment, patients with cancer or symptomatic PE at baseline were at higher risk of subsequent VTE (odds ratio [OR]=3.7; 95% confidence interval [CI], 1.3-11; OR=3.4; 95% CI, 1.55-7.3), respectively. These findings were unchanged when analysis was restricted to subjects for whom all data were available. Similarly, there was no significant difference among the groups in the incidence of major hemorrhage (2.1%, 1.7%, 1.3%, respectively), death (3.1%, 3.7%, 2.2%, respectively), or thrombocytopenia. Adherence to enoxaparin in both groups was better than for unfractionated heparin group (83.6% and 85.3% vs 75.9%, respectively).

BACKGROUND: Several studies have shown that initial treatment with subcutaneous low-molecular-weight heparin is as effective as intravenous unfractionated heparin in preventing the sequelae of VTE. This randomized controlled trial addressed this issue with a large population that included patients with pulmonary embolus (PE).

POPULATION STUDIED: A total of 900 patients from 74 hospitals in 16 countries were enrolled. Subjects were adults with venogram- or ultrasound-proven lower extremity deep venous thrombosis, symptomatic PE with high-probability ventilation-perfusion (V/Q) scan, or a positive angiogram with radiologic evidence of a lower extremity VTE. Exclusion criteria included previous administration of heparin or warfarin for more than 24 hours, risk for hemorrhage, and allergies to the medications or to pork products. The average age was 61 years; 55% were men. Twenty-four percent had had a previous VTE; 16% had cancer; and 32% had a concurrent PE. The study population seems to be similar to that of a family physician., although more information about referral pattern and local diagnostic and therapeutic protocols would be valuable.

STUDY DESIGN AND VALIDITY: This was a randomized unblinded trial. Subjects received 1 of 3 antithrombotic regimens: heparin bolus and continuous infusion to achieve a target activated partial thromboplastin time of 55 to 80 seconds, enoxaparin 1 mg per kg twice daily, or enoxaparin 1.5 mg per kg once daily. These regimens were continued for at least 5 days. Warfarin was started within the first 3 days and was continued for at least 3 months, adjusted to maintain an international normalized ratio between 2.0 and 3.0. All subjects received baseline V/Q scans or angiograms. Although the clinicians were not masked to treatment status, all imaging studies and outcomes were reviewed by committees masked to treatment status. The maker of enoxaparin sponsored and performed the study.

OUTCOMES MEASURED: The major outcomes were recurrence or worsening of VTE or PE, major hemorrhage (ie, >2.0 g/L hemoglobin drop, requiring transfusion of 2 or more units, bleeding requiring intervention, or death), thrombocytopenia, or other side effects. Cost and patient satisfaction were not addressed.

RESULTS: The groups were similar at baseline. There was no significant difference in recurrence or worsening of VTE among patients in the unfractionated heparin group (4.1%), enoxaparin daily group (4.4%), and enoxaparin twice-daily group (2.9%). New PE was rare in all 3 groups (4/900). Regardless of treatment, patients with cancer or symptomatic PE at baseline were at higher risk of subsequent VTE (odds ratio [OR]=3.7; 95% confidence interval [CI], 1.3-11; OR=3.4; 95% CI, 1.55-7.3), respectively. These findings were unchanged when analysis was restricted to subjects for whom all data were available. Similarly, there was no significant difference among the groups in the incidence of major hemorrhage (2.1%, 1.7%, 1.3%, respectively), death (3.1%, 3.7%, 2.2%, respectively), or thrombocytopenia. Adherence to enoxaparin in both groups was better than for unfractionated heparin group (83.6% and 85.3% vs 75.9%, respectively).