Clinical Inquiries

Evidence summary

Prevalence and types

In areas where iodine supplementation is routine, the prevalence of goiter is estimated to be 4% to 7%; however, autopsy studies show a 50% prevalence of nodules, most of which are multinodular goiter.¹ Multinodular goiter is diagnosed in up to 5% of the general population and can be classified as euthyroid (“nontoxic”), hypothyroid, or hyperthyroid (“toxic”).¹ Multinodular goiter is the most common diagnosis in cases of euthyroid goiter, but other conditions such as diffuse goiter (often idiopathic), thyroiditis, and neoplasms can also present in a euthyroid state.

Diagnosis: Exam and imaging

Studies show variable correlation between physical exam findings and findings on imaging studies. In a retrospective chart review, ultrasound findings differed from clinical exam findings in 63% of cases.² Thyroid ultrasound is less expensive and less invasive than other imaging modalities, provides excellent visualization of thyroid structure and the nature of cysts and nodules, and allows for estimation of thyroid size.

Computed tomography and magnetic resonance imaging perform better for visualization of extension of thyroid tissue substernally and are also preferred for evaluation of the neck in cases of severe local complications of goiter, such as compressive symptoms.³

The malignant potential in multinodular goiter (2%–4%) is similar to that of solitary nodules (4%–6%).³ Therefore, any dominant nodule in a multinodular goiter should be evaluated the same way one would evaluate a solitary nodule.

Treatment and follow-up

Patients with a reassuring initial work-up can be followed clinically and should be assessed with serial clinical evaluations. No evidence could be found regarding optimal intervals for examination and testing; yearly exams and TSH testing are considered adequate by some experts.⁴

Because a few non-benign conditions such as thyroiditis and neoplasm can sometimes present in a euthyroid state, the clinician should be alert for any physical exam or laboratory changes. If any changes occur, then further workup is indicated.

Suppressive therapy with thyroxine is an option for decreasing thyroid size in euthyroid goiter, but this therapy remains controversial. One placebo-controlled trial of thyroid suppression in nontoxic multinodular goiter showed regression of thyroid size with suppressive therapy (58% reduction in size in treatment group vs 5% reduction in control group). However, not all goiters responded to this therapy, and the thyroid size returned to pretreatment size within 9 months of discontinuation of suppressive therapy.⁵

Many experts argue against the use of suppressive therapy in long-standing goiters, citing less response from these patients, along with concern about side effects and possible oversuppression, but the evidence in this area is limited. Patients who are treated with thyroxine should be followed for possible side effects of the medication, including arrhythmia and osteopenia, particularly in elderly patients and those who take the medication for long periods.

Recommendations of others

Guidelines from the American Association of Clinical Endocrinology’s Task Force on Thyroid Nodules, released in 2006, recommends ultrasound be used routinely in the case of multinodular goiter to assist with diagnosis, detect suspicious nodules that may require biopsy, and to serve as an objective baseline measure. This group recommends against use of suppression therapy in long-standing goiters.⁶

Evidence summary

Prevalence and types

In areas where iodine supplementation is routine, the prevalence of goiter is estimated to be 4% to 7%; however, autopsy studies show a 50% prevalence of nodules, most of which are multinodular goiter.¹ Multinodular goiter is diagnosed in up to 5% of the general population and can be classified as euthyroid (“nontoxic”), hypothyroid, or hyperthyroid (“toxic”).¹ Multinodular goiter is the most common diagnosis in cases of euthyroid goiter, but other conditions such as diffuse goiter (often idiopathic), thyroiditis, and neoplasms can also present in a euthyroid state.

Diagnosis: Exam and imaging

Studies show variable correlation between physical exam findings and findings on imaging studies. In a retrospective chart review, ultrasound findings differed from clinical exam findings in 63% of cases.² Thyroid ultrasound is less expensive and less invasive than other imaging modalities, provides excellent visualization of thyroid structure and the nature of cysts and nodules, and allows for estimation of thyroid size.

Computed tomography and magnetic resonance imaging perform better for visualization of extension of thyroid tissue substernally and are also preferred for evaluation of the neck in cases of severe local complications of goiter, such as compressive symptoms.³

The malignant potential in multinodular goiter (2%–4%) is similar to that of solitary nodules (4%–6%).³ Therefore, any dominant nodule in a multinodular goiter should be evaluated the same way one would evaluate a solitary nodule.

Treatment and follow-up

Patients with a reassuring initial work-up can be followed clinically and should be assessed with serial clinical evaluations. No evidence could be found regarding optimal intervals for examination and testing; yearly exams and TSH testing are considered adequate by some experts.⁴

Because a few non-benign conditions such as thyroiditis and neoplasm can sometimes present in a euthyroid state, the clinician should be alert for any physical exam or laboratory changes. If any changes occur, then further workup is indicated.

Suppressive therapy with thyroxine is an option for decreasing thyroid size in euthyroid goiter, but this therapy remains controversial. One placebo-controlled trial of thyroid suppression in nontoxic multinodular goiter showed regression of thyroid size with suppressive therapy (58% reduction in size in treatment group vs 5% reduction in control group). However, not all goiters responded to this therapy, and the thyroid size returned to pretreatment size within 9 months of discontinuation of suppressive therapy.⁵

Many experts argue against the use of suppressive therapy in long-standing goiters, citing less response from these patients, along with concern about side effects and possible oversuppression, but the evidence in this area is limited. Patients who are treated with thyroxine should be followed for possible side effects of the medication, including arrhythmia and osteopenia, particularly in elderly patients and those who take the medication for long periods.

Recommendations of others

Guidelines from the American Association of Clinical Endocrinology’s Task Force on Thyroid Nodules, released in 2006, recommends ultrasound be used routinely in the case of multinodular goiter to assist with diagnosis, detect suspicious nodules that may require biopsy, and to serve as an objective baseline measure. This group recommends against use of suppression therapy in long-standing goiters.⁶

Evidence summary

Prevalence and types

In areas where iodine supplementation is routine, the prevalence of goiter is estimated to be 4% to 7%; however, autopsy studies show a 50% prevalence of nodules, most of which are multinodular goiter.¹ Multinodular goiter is diagnosed in up to 5% of the general population and can be classified as euthyroid (“nontoxic”), hypothyroid, or hyperthyroid (“toxic”).¹ Multinodular goiter is the most common diagnosis in cases of euthyroid goiter, but other conditions such as diffuse goiter (often idiopathic), thyroiditis, and neoplasms can also present in a euthyroid state.

Diagnosis: Exam and imaging

Studies show variable correlation between physical exam findings and findings on imaging studies. In a retrospective chart review, ultrasound findings differed from clinical exam findings in 63% of cases.² Thyroid ultrasound is less expensive and less invasive than other imaging modalities, provides excellent visualization of thyroid structure and the nature of cysts and nodules, and allows for estimation of thyroid size.

Computed tomography and magnetic resonance imaging perform better for visualization of extension of thyroid tissue substernally and are also preferred for evaluation of the neck in cases of severe local complications of goiter, such as compressive symptoms.³

The malignant potential in multinodular goiter (2%–4%) is similar to that of solitary nodules (4%–6%).³ Therefore, any dominant nodule in a multinodular goiter should be evaluated the same way one would evaluate a solitary nodule.

Treatment and follow-up

Patients with a reassuring initial work-up can be followed clinically and should be assessed with serial clinical evaluations. No evidence could be found regarding optimal intervals for examination and testing; yearly exams and TSH testing are considered adequate by some experts.⁴

Because a few non-benign conditions such as thyroiditis and neoplasm can sometimes present in a euthyroid state, the clinician should be alert for any physical exam or laboratory changes. If any changes occur, then further workup is indicated.

Suppressive therapy with thyroxine is an option for decreasing thyroid size in euthyroid goiter, but this therapy remains controversial. One placebo-controlled trial of thyroid suppression in nontoxic multinodular goiter showed regression of thyroid size with suppressive therapy (58% reduction in size in treatment group vs 5% reduction in control group). However, not all goiters responded to this therapy, and the thyroid size returned to pretreatment size within 9 months of discontinuation of suppressive therapy.⁵

Many experts argue against the use of suppressive therapy in long-standing goiters, citing less response from these patients, along with concern about side effects and possible oversuppression, but the evidence in this area is limited. Patients who are treated with thyroxine should be followed for possible side effects of the medication, including arrhythmia and osteopenia, particularly in elderly patients and those who take the medication for long periods.

Recommendations of others

Guidelines from the American Association of Clinical Endocrinology’s Task Force on Thyroid Nodules, released in 2006, recommends ultrasound be used routinely in the case of multinodular goiter to assist with diagnosis, detect suspicious nodules that may require biopsy, and to serve as an objective baseline measure. This group recommends against use of suppression therapy in long-standing goiters.⁶

Evidence summary

Radiographic imaging to rule out appendicitis has become more commonplace, but it comes with an increased financial cost and additional delay in surgical intervention. Knowing the accuracy of common diagnostic tests may reduce the need for confirmatory imaging studies that increase both cost and time to surgery.

High levels of 2 or more inflammatory values are helpful

A meta-analysis of patients hospitalized for suspected acute appendicitis analyzed 28 different diagnostic variables in 24 studies.¹ Variables included WBC, granulocyte count, PMN proportion, CRP level, and body temperature; histopathology was the gold standard. In no circumstance did an isolated elevation of any 1 factor result in a significant LR+. In addition, the absence of any 1 variable failed to yield a LR– <0.01 (low enough to exclude appendicitis).

Clinicians inherently combine multiple variables when evaluating patients, and when evaluating patients with abdominal pain, this technique can result in identification of adequate likelihood ratios (TABLE).¹ In general, when 2 or more of the aforementioned inflammatory variables are present, the diagnosis of acute appendicitis is likely. When all markers of inflammation are normal, though acute appendicitis is less likely, the power is insufficient to exclude it as a possible diagnosis.

The value of CRP in the evaluation of suspected appendicitis was confirmed in a retrospective evaluation of 566 patients who underwent appendectomies.² The sensitivity and specificity of the test improved depending on the duration of symptoms for both appendicitis and ruptured appendicitis. For appendicitis, CRP levels >1.4, 4.0, and 10.5 on Days 1, 2, and 3 had sensitivities/specificities of 0.38/0.81, 0.63/0.78, and 0.72/0.83, respectively. For ruptured appendicitis, levels of 3.3, 8.5, and 12.0 on Days 1, 2, and 3 had sensitivities/specificities of 0.77/0.89, 0.70/0.95, and 0.90/0.96, respectively.

Enlarged appendix with inflammatory changes to mesenteric fatIn a series of 439 patients with symptoms suggestive of acute appendicitis, those with confirmed appendicitis (n=101) had a mean WBC count of 14.8 K/μL (95% CI, 13.9–15.8) and a mean neutrophil percentage of 82 (95% CI, 80–84).¹ In contrast, those without appendicitis (n=338) had a mean WBC count of 9.2 K/μL (95% CI, 9.0–9.4) and a mean neutrophil percentage of 68 (95% CI, 66–70).

TABLE
How much do the inflammatory markers tell us? A look at likelihood ratios for appendicitis

Recommendations from others

A review of medical and professional associations revealed no official guidelines regarding the evaluation of suspected acute appendicitis. Surgical textbooks confirm that the diagnosis of acute appendicitis is made primarily by history and examination, with help from laboratory and radiographic studies.³

Evidence summary

Radiographic imaging to rule out appendicitis has become more commonplace, but it comes with an increased financial cost and additional delay in surgical intervention. Knowing the accuracy of common diagnostic tests may reduce the need for confirmatory imaging studies that increase both cost and time to surgery.

High levels of 2 or more inflammatory values are helpful

A meta-analysis of patients hospitalized for suspected acute appendicitis analyzed 28 different diagnostic variables in 24 studies.¹ Variables included WBC, granulocyte count, PMN proportion, CRP level, and body temperature; histopathology was the gold standard. In no circumstance did an isolated elevation of any 1 factor result in a significant LR+. In addition, the absence of any 1 variable failed to yield a LR– <0.01 (low enough to exclude appendicitis).

Clinicians inherently combine multiple variables when evaluating patients, and when evaluating patients with abdominal pain, this technique can result in identification of adequate likelihood ratios (TABLE).¹ In general, when 2 or more of the aforementioned inflammatory variables are present, the diagnosis of acute appendicitis is likely. When all markers of inflammation are normal, though acute appendicitis is less likely, the power is insufficient to exclude it as a possible diagnosis.

The value of CRP in the evaluation of suspected appendicitis was confirmed in a retrospective evaluation of 566 patients who underwent appendectomies.² The sensitivity and specificity of the test improved depending on the duration of symptoms for both appendicitis and ruptured appendicitis. For appendicitis, CRP levels >1.4, 4.0, and 10.5 on Days 1, 2, and 3 had sensitivities/specificities of 0.38/0.81, 0.63/0.78, and 0.72/0.83, respectively. For ruptured appendicitis, levels of 3.3, 8.5, and 12.0 on Days 1, 2, and 3 had sensitivities/specificities of 0.77/0.89, 0.70/0.95, and 0.90/0.96, respectively.

Enlarged appendix with inflammatory changes to mesenteric fatIn a series of 439 patients with symptoms suggestive of acute appendicitis, those with confirmed appendicitis (n=101) had a mean WBC count of 14.8 K/μL (95% CI, 13.9–15.8) and a mean neutrophil percentage of 82 (95% CI, 80–84).¹ In contrast, those without appendicitis (n=338) had a mean WBC count of 9.2 K/μL (95% CI, 9.0–9.4) and a mean neutrophil percentage of 68 (95% CI, 66–70).

TABLE
How much do the inflammatory markers tell us? A look at likelihood ratios for appendicitis

Recommendations from others

A review of medical and professional associations revealed no official guidelines regarding the evaluation of suspected acute appendicitis. Surgical textbooks confirm that the diagnosis of acute appendicitis is made primarily by history and examination, with help from laboratory and radiographic studies.³

Evidence summary

Radiographic imaging to rule out appendicitis has become more commonplace, but it comes with an increased financial cost and additional delay in surgical intervention. Knowing the accuracy of common diagnostic tests may reduce the need for confirmatory imaging studies that increase both cost and time to surgery.

High levels of 2 or more inflammatory values are helpful

A meta-analysis of patients hospitalized for suspected acute appendicitis analyzed 28 different diagnostic variables in 24 studies.¹ Variables included WBC, granulocyte count, PMN proportion, CRP level, and body temperature; histopathology was the gold standard. In no circumstance did an isolated elevation of any 1 factor result in a significant LR+. In addition, the absence of any 1 variable failed to yield a LR– <0.01 (low enough to exclude appendicitis).

Clinicians inherently combine multiple variables when evaluating patients, and when evaluating patients with abdominal pain, this technique can result in identification of adequate likelihood ratios (TABLE).¹ In general, when 2 or more of the aforementioned inflammatory variables are present, the diagnosis of acute appendicitis is likely. When all markers of inflammation are normal, though acute appendicitis is less likely, the power is insufficient to exclude it as a possible diagnosis.

The value of CRP in the evaluation of suspected appendicitis was confirmed in a retrospective evaluation of 566 patients who underwent appendectomies.² The sensitivity and specificity of the test improved depending on the duration of symptoms for both appendicitis and ruptured appendicitis. For appendicitis, CRP levels >1.4, 4.0, and 10.5 on Days 1, 2, and 3 had sensitivities/specificities of 0.38/0.81, 0.63/0.78, and 0.72/0.83, respectively. For ruptured appendicitis, levels of 3.3, 8.5, and 12.0 on Days 1, 2, and 3 had sensitivities/specificities of 0.77/0.89, 0.70/0.95, and 0.90/0.96, respectively.

Enlarged appendix with inflammatory changes to mesenteric fatIn a series of 439 patients with symptoms suggestive of acute appendicitis, those with confirmed appendicitis (n=101) had a mean WBC count of 14.8 K/μL (95% CI, 13.9–15.8) and a mean neutrophil percentage of 82 (95% CI, 80–84).¹ In contrast, those without appendicitis (n=338) had a mean WBC count of 9.2 K/μL (95% CI, 9.0–9.4) and a mean neutrophil percentage of 68 (95% CI, 66–70).

TABLE
How much do the inflammatory markers tell us? A look at likelihood ratios for appendicitis

Recommendations from others

A review of medical and professional associations revealed no official guidelines regarding the evaluation of suspected acute appendicitis. Surgical textbooks confirm that the diagnosis of acute appendicitis is made primarily by history and examination, with help from laboratory and radiographic studies.³

Evidence summary

There is a theoretical risk of decreased hormonal contraceptive efficacy for obese women (defined as those having a body-mass index [BMI] ≥30 kg/m²) due to increased metabolism of the hormones resulting in lower serum levels. With the growing epidemic of obesity, concern over the efficacy of hormonal contraception has grown. At this time, however, only a few published studies evaluating contraception have specifically examined the effect of body weight on efficacy.

Pregnancy risk doubled among heavier patients on OCs

Some studies have shown a possible association between obesity and higher rates of pregnancy among women using oral contraceptives for birth control.

One retrospective cohort analysis found that women weighing >70.5 kg had an increased risk of pregnancy compared with women of lower weight (relative risk [RR]=1.6; 95% confidence interval [CI], 1.1–2.4), after controlling for parity.¹ Pill compliance was not accounted for in this study. A follow-up case-control study demonstrated that the risk of pregnancy for consistent pill users doubled for women with a BMI >27.3 (odds ratio [OR]=2.17; 95% CI, 1.38–3.41); results were similar for those with a BMI >32.2 (OR=2.2; 95% CI, 1.18–4.20).²

Another large cohort study did not find any association between failure of the oral contraceptive pill or progestin-only pill and obesity; however, the total number of pregnancies among obese women was too small to achieve statistical significance.³ In a randomized trial studying the efficacy of an extended-cycle oral contraceptive (Seasonale), no woman weighing >90 kg became pregnant.⁴

When it comes to the combination contraceptive patch, the data show a significant association between baseline body weight and pregnancy. In an analysis of pooled data, 5 of 15 pregnancies occurred in a subgroup of women with a baseline body weight ≥90 kg. Less than 3% of the study population weighed more than 90 kg. Specific data for this subgroup were not presented in the study results, so measures of effect cannot be calculated. The mechanism of the decreased efficacy of the combined contraceptive patch for obese women is unclear.⁵

DMPA and vaginal ring may be a better option for obese women

Data suggest that increased body weight does not decrease the efficacy of DMPA. In 2 large open-label studies, no pregnancies were observed, regardless of BMI.⁶ Similarly, the efficacy of the contraceptive vaginal ring does not appear to be affected by body weight, but the mean BMI in intent-to-treat population studies was only 22.9±2.9.⁷

A secondary analysis of the contraceptive vaginal ring efficacy trials did not show an increased pregnancy rate among heavier women.⁸ Of note: A higher body weight appeared to be associated with increased likelihood of ovulation using the contraceptive vaginal ring, though it did not lead to any pregnancies in a multicenter study.⁹

The data on the levonorgestrel intrauterine system do not examine weight and efficacy.¹⁰

Recommendations from others

The World Health Organization generally recommends hormonal contraceptives as safe for obese women. The group acknowledges that data are limited regarding effectiveness of oral contraceptives, and efficacy may be lower for the combination contraceptive patch when used by obese women.¹¹

The American College of Obstetrics and Gynecology (ACOG) suggests that despite the possibility of higher failure rates with oral and transdermal contraception, motivated obese women should still be encouraged to use these methods preferentially over known less effective methods.¹² In addition, ACOG also notes that no higher rates of pregnancy are observed among overweight women using DMPA.

Evidence summary

There is a theoretical risk of decreased hormonal contraceptive efficacy for obese women (defined as those having a body-mass index [BMI] ≥30 kg/m²) due to increased metabolism of the hormones resulting in lower serum levels. With the growing epidemic of obesity, concern over the efficacy of hormonal contraception has grown. At this time, however, only a few published studies evaluating contraception have specifically examined the effect of body weight on efficacy.

Pregnancy risk doubled among heavier patients on OCs

Some studies have shown a possible association between obesity and higher rates of pregnancy among women using oral contraceptives for birth control.

One retrospective cohort analysis found that women weighing >70.5 kg had an increased risk of pregnancy compared with women of lower weight (relative risk [RR]=1.6; 95% confidence interval [CI], 1.1–2.4), after controlling for parity.¹ Pill compliance was not accounted for in this study. A follow-up case-control study demonstrated that the risk of pregnancy for consistent pill users doubled for women with a BMI >27.3 (odds ratio [OR]=2.17; 95% CI, 1.38–3.41); results were similar for those with a BMI >32.2 (OR=2.2; 95% CI, 1.18–4.20).²

Another large cohort study did not find any association between failure of the oral contraceptive pill or progestin-only pill and obesity; however, the total number of pregnancies among obese women was too small to achieve statistical significance.³ In a randomized trial studying the efficacy of an extended-cycle oral contraceptive (Seasonale), no woman weighing >90 kg became pregnant.⁴

When it comes to the combination contraceptive patch, the data show a significant association between baseline body weight and pregnancy. In an analysis of pooled data, 5 of 15 pregnancies occurred in a subgroup of women with a baseline body weight ≥90 kg. Less than 3% of the study population weighed more than 90 kg. Specific data for this subgroup were not presented in the study results, so measures of effect cannot be calculated. The mechanism of the decreased efficacy of the combined contraceptive patch for obese women is unclear.⁵

DMPA and vaginal ring may be a better option for obese women

Data suggest that increased body weight does not decrease the efficacy of DMPA. In 2 large open-label studies, no pregnancies were observed, regardless of BMI.⁶ Similarly, the efficacy of the contraceptive vaginal ring does not appear to be affected by body weight, but the mean BMI in intent-to-treat population studies was only 22.9±2.9.⁷

A secondary analysis of the contraceptive vaginal ring efficacy trials did not show an increased pregnancy rate among heavier women.⁸ Of note: A higher body weight appeared to be associated with increased likelihood of ovulation using the contraceptive vaginal ring, though it did not lead to any pregnancies in a multicenter study.⁹

The data on the levonorgestrel intrauterine system do not examine weight and efficacy.¹⁰

Recommendations from others

The World Health Organization generally recommends hormonal contraceptives as safe for obese women. The group acknowledges that data are limited regarding effectiveness of oral contraceptives, and efficacy may be lower for the combination contraceptive patch when used by obese women.¹¹

The American College of Obstetrics and Gynecology (ACOG) suggests that despite the possibility of higher failure rates with oral and transdermal contraception, motivated obese women should still be encouraged to use these methods preferentially over known less effective methods.¹² In addition, ACOG also notes that no higher rates of pregnancy are observed among overweight women using DMPA.

Evidence summary

There is a theoretical risk of decreased hormonal contraceptive efficacy for obese women (defined as those having a body-mass index [BMI] ≥30 kg/m²) due to increased metabolism of the hormones resulting in lower serum levels. With the growing epidemic of obesity, concern over the efficacy of hormonal contraception has grown. At this time, however, only a few published studies evaluating contraception have specifically examined the effect of body weight on efficacy.

Pregnancy risk doubled among heavier patients on OCs

Some studies have shown a possible association between obesity and higher rates of pregnancy among women using oral contraceptives for birth control.

One retrospective cohort analysis found that women weighing >70.5 kg had an increased risk of pregnancy compared with women of lower weight (relative risk [RR]=1.6; 95% confidence interval [CI], 1.1–2.4), after controlling for parity.¹ Pill compliance was not accounted for in this study. A follow-up case-control study demonstrated that the risk of pregnancy for consistent pill users doubled for women with a BMI >27.3 (odds ratio [OR]=2.17; 95% CI, 1.38–3.41); results were similar for those with a BMI >32.2 (OR=2.2; 95% CI, 1.18–4.20).²

Another large cohort study did not find any association between failure of the oral contraceptive pill or progestin-only pill and obesity; however, the total number of pregnancies among obese women was too small to achieve statistical significance.³ In a randomized trial studying the efficacy of an extended-cycle oral contraceptive (Seasonale), no woman weighing >90 kg became pregnant.⁴

When it comes to the combination contraceptive patch, the data show a significant association between baseline body weight and pregnancy. In an analysis of pooled data, 5 of 15 pregnancies occurred in a subgroup of women with a baseline body weight ≥90 kg. Less than 3% of the study population weighed more than 90 kg. Specific data for this subgroup were not presented in the study results, so measures of effect cannot be calculated. The mechanism of the decreased efficacy of the combined contraceptive patch for obese women is unclear.⁵

DMPA and vaginal ring may be a better option for obese women

Data suggest that increased body weight does not decrease the efficacy of DMPA. In 2 large open-label studies, no pregnancies were observed, regardless of BMI.⁶ Similarly, the efficacy of the contraceptive vaginal ring does not appear to be affected by body weight, but the mean BMI in intent-to-treat population studies was only 22.9±2.9.⁷

A secondary analysis of the contraceptive vaginal ring efficacy trials did not show an increased pregnancy rate among heavier women.⁸ Of note: A higher body weight appeared to be associated with increased likelihood of ovulation using the contraceptive vaginal ring, though it did not lead to any pregnancies in a multicenter study.⁹

The data on the levonorgestrel intrauterine system do not examine weight and efficacy.¹⁰

Recommendations from others

The World Health Organization generally recommends hormonal contraceptives as safe for obese women. The group acknowledges that data are limited regarding effectiveness of oral contraceptives, and efficacy may be lower for the combination contraceptive patch when used by obese women.¹¹

The American College of Obstetrics and Gynecology (ACOG) suggests that despite the possibility of higher failure rates with oral and transdermal contraception, motivated obese women should still be encouraged to use these methods preferentially over known less effective methods.¹² In addition, ACOG also notes that no higher rates of pregnancy are observed among overweight women using DMPA.

Evidence summary

Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;¹ 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.^1,2

Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.^1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.

Intrapartum antibiotics probably reduce sepsis

Although few well-designed trials stand out, a Cochrane review⁴ summarizing 2 relevant studies is available. Gibbs et al³ performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.³ Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.

Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.⁴

The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).¹ There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).⁴

Recommendations from others

A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics⁵ recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).⁶ Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;¹ 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.^1,2

Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.^1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.

Intrapartum antibiotics probably reduce sepsis

Although few well-designed trials stand out, a Cochrane review⁴ summarizing 2 relevant studies is available. Gibbs et al³ performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.³ Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.

Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.⁴

The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).¹ There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).⁴

Recommendations from others

A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics⁵ recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).⁶ Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;¹ 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.^1,2

Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.^1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.

Intrapartum antibiotics probably reduce sepsis

Although few well-designed trials stand out, a Cochrane review⁴ summarizing 2 relevant studies is available. Gibbs et al³ performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.³ Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.

Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.⁴

The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).¹ There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).⁴

Recommendations from others

A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics⁵ recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).⁶ Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

A Cochrane review¹ of antibiotic use for pertussis prophylaxis, including studies published through 2002, found only 2 randomized, well-controlled trials (RCTs) that compared attack rates between contacts receiving placebo or antibiotic therapy. Neither trial included infants under age 6 months. The reviewers concluded that evidence was insufficient to determine a treatment benefit. The larger study² included 310 household or family contacts, randomized by household to 10 days of erythromycin estolate or placebo. Positive cultures or clinical pertussis developed in 4.8% of treated contacts and 6.1% of controls (relative risk [RR]=0.8; 95% confidence interval [CI], 0.3–2.2). Adverse side effects occurred in 34% of the erythromycin group and 16% of controls (RR=2.2; 95% CI, 1.4–3.3; number needed to harm=5.6).

Focus on those at high risk

Despite the paucity of RCTs, the CDC and other public health agency guidelines recommend postexposure prophylaxis for certain close contacts to protect high-risk individuals, defined as those who could develop severe disease or experience adverse outcomes if pertussis developed.^3-6

High-risk individuals include:

• Infants <1 year old
• Pregnant women in their third trimester
• the immunocompromised
• those with underlying medical condition such as chronic lung disease, respiratory insufficiency, or cystic fibrosis
• those who have close contact with any of the above high-risk individuals (eg, household members or health-care workers providing face-to-face care).

Close contact is defined as:

• confinement in a closed space for >1 hour with a known case, or
• direct contact with respiratory, oral, or nasal secretions from a symptomatic person, or
• face-to-face exposure within 3 feet of a symptomatic patient.

TABLE
Recommendations for pertussis prophylaxis

Clinical trials involving such patients have not been conducted.^6,7 Maintenance of active vaccination status is an effective means to prevent the spread of pertussis among the general population and has been suggested as a means to control local outbreaks,⁶ though it has no role in immediate postexposure prophylaxis for an individual. In one RCT, no (0/60) fully immunized child in a household with pertussis developed whooping cough, with or without antibiotic prophylaxis. Among unimmunized children, pertussis developed in 4/20 receiving erythromycin prophylaxis and 2/11 receiving placebo.

Macrolides (erythromycin, clarithromycin, or azithromycin) are recommended for postexposure prophylaxis. Trimethoprim-sulfamethoxazole is a second-line agent.⁵ A short course of erythromycin (7 days), azithromycin (3–5 days), or clarithromycin (7 days) is as effective as a 2-week course of erythromycin in eradicating Bordetella pertussis from the nasopharynx.

Recommendations from others

Recommendations from others are in the TABLE.

Evidence summary

A Cochrane review¹ of antibiotic use for pertussis prophylaxis, including studies published through 2002, found only 2 randomized, well-controlled trials (RCTs) that compared attack rates between contacts receiving placebo or antibiotic therapy. Neither trial included infants under age 6 months. The reviewers concluded that evidence was insufficient to determine a treatment benefit. The larger study² included 310 household or family contacts, randomized by household to 10 days of erythromycin estolate or placebo. Positive cultures or clinical pertussis developed in 4.8% of treated contacts and 6.1% of controls (relative risk [RR]=0.8; 95% confidence interval [CI], 0.3–2.2). Adverse side effects occurred in 34% of the erythromycin group and 16% of controls (RR=2.2; 95% CI, 1.4–3.3; number needed to harm=5.6).

Focus on those at high risk

Despite the paucity of RCTs, the CDC and other public health agency guidelines recommend postexposure prophylaxis for certain close contacts to protect high-risk individuals, defined as those who could develop severe disease or experience adverse outcomes if pertussis developed.^3-6

High-risk individuals include:

• Infants <1 year old
• Pregnant women in their third trimester
• the immunocompromised
• those with underlying medical condition such as chronic lung disease, respiratory insufficiency, or cystic fibrosis
• those who have close contact with any of the above high-risk individuals (eg, household members or health-care workers providing face-to-face care).

Close contact is defined as:

• confinement in a closed space for >1 hour with a known case, or
• direct contact with respiratory, oral, or nasal secretions from a symptomatic person, or
• face-to-face exposure within 3 feet of a symptomatic patient.

TABLE
Recommendations for pertussis prophylaxis

Clinical trials involving such patients have not been conducted.^6,7 Maintenance of active vaccination status is an effective means to prevent the spread of pertussis among the general population and has been suggested as a means to control local outbreaks,⁶ though it has no role in immediate postexposure prophylaxis for an individual. In one RCT, no (0/60) fully immunized child in a household with pertussis developed whooping cough, with or without antibiotic prophylaxis. Among unimmunized children, pertussis developed in 4/20 receiving erythromycin prophylaxis and 2/11 receiving placebo.

Macrolides (erythromycin, clarithromycin, or azithromycin) are recommended for postexposure prophylaxis. Trimethoprim-sulfamethoxazole is a second-line agent.⁵ A short course of erythromycin (7 days), azithromycin (3–5 days), or clarithromycin (7 days) is as effective as a 2-week course of erythromycin in eradicating Bordetella pertussis from the nasopharynx.

Recommendations from others

Recommendations from others are in the TABLE.

Evidence summary

A Cochrane review¹ of antibiotic use for pertussis prophylaxis, including studies published through 2002, found only 2 randomized, well-controlled trials (RCTs) that compared attack rates between contacts receiving placebo or antibiotic therapy. Neither trial included infants under age 6 months. The reviewers concluded that evidence was insufficient to determine a treatment benefit. The larger study² included 310 household or family contacts, randomized by household to 10 days of erythromycin estolate or placebo. Positive cultures or clinical pertussis developed in 4.8% of treated contacts and 6.1% of controls (relative risk [RR]=0.8; 95% confidence interval [CI], 0.3–2.2). Adverse side effects occurred in 34% of the erythromycin group and 16% of controls (RR=2.2; 95% CI, 1.4–3.3; number needed to harm=5.6).

Focus on those at high risk

Despite the paucity of RCTs, the CDC and other public health agency guidelines recommend postexposure prophylaxis for certain close contacts to protect high-risk individuals, defined as those who could develop severe disease or experience adverse outcomes if pertussis developed.^3-6

High-risk individuals include:

• Infants <1 year old
• Pregnant women in their third trimester
• the immunocompromised
• those with underlying medical condition such as chronic lung disease, respiratory insufficiency, or cystic fibrosis
• those who have close contact with any of the above high-risk individuals (eg, household members or health-care workers providing face-to-face care).

Close contact is defined as:

• confinement in a closed space for >1 hour with a known case, or
• direct contact with respiratory, oral, or nasal secretions from a symptomatic person, or
• face-to-face exposure within 3 feet of a symptomatic patient.

TABLE
Recommendations for pertussis prophylaxis

Clinical trials involving such patients have not been conducted.^6,7 Maintenance of active vaccination status is an effective means to prevent the spread of pertussis among the general population and has been suggested as a means to control local outbreaks,⁶ though it has no role in immediate postexposure prophylaxis for an individual. In one RCT, no (0/60) fully immunized child in a household with pertussis developed whooping cough, with or without antibiotic prophylaxis. Among unimmunized children, pertussis developed in 4/20 receiving erythromycin prophylaxis and 2/11 receiving placebo.

Macrolides (erythromycin, clarithromycin, or azithromycin) are recommended for postexposure prophylaxis. Trimethoprim-sulfamethoxazole is a second-line agent.⁵ A short course of erythromycin (7 days), azithromycin (3–5 days), or clarithromycin (7 days) is as effective as a 2-week course of erythromycin in eradicating Bordetella pertussis from the nasopharynx.

Recommendations from others

Recommendations from others are in the TABLE.

Evidence summary

Two meningococcal vaccines are currently available in the US: tetravalent polysaccharide vaccine (MPSV4) and tetravalent polysaccharide-protein conjugate vaccine (MCV4). Both protect against serogroups A, C, Y, and W-135, but not against serogroup B, which is the most prevalent. A vaccine for serogroup B is under development.

MPSV4 is licensed for ages 2 years and up, but its poor immunogenicity in infants, lack of memory and booster response, and relatively short duration of protection have restricted its use. MCV4 is licensed for 11- to 55-year-olds and is the preferred vaccine in this age group, since it provides longer duration of immunity and reduces nasopharyngeal carriage.¹

Infants and freshman are especially vulnerable

Using active community surveillance from 1991 to 2002, Centers for Disease Control and Prevention (CDC) data² found annual rates of meningococcal disease in the US of 0.5 to 1.1 per 100,000. The highest rates were found in children under age 2. Infants younger than 12 months of age were especially vulnerable (rate 9/100,000), with more than 50% of cases caused by serogroup B.

A 1998–1999 prospective surveillance study³ including 50 state health departments and 231 college health centers identified 96 cases of meningococcal disease in college students (incidence 0.7/100,000). Freshmen living in dormitories had an elevated risk of meningococcal disease compared with other undergraduates or nonstudents of the same age (incidence 5.1/100,000; adjusted relative risk=3.6 [95% confidence interval [CI], 1.6–8.5). Sixty-eight percent had illness due to a vaccine-preventable serogroup.

Using CDC incidence data, a cost-effectiveness model⁴ compared hypothetical vaccination strategies targeting US infants (3 doses), toddlers (1 dose), or 11-year-olds (1 dose). Routine MCV4 vaccination of all 11-year-olds would prevent 270 cases and 36 deaths in this cohort over their next 22 years. For a toddler cohort, vaccination would prevent 385 cases and 33 deaths; for infants, 447 cases and 36 deaths. Conjugate meningococcal vaccines for serogroups A and C have been tested and used in children in other countries, and appear safe and effective, but are not yet available in the US. An application has been submitted for FDA approval of MCV4 for 2- to 10-year-olds.

Herd immunity may expand benefit of vaccination

A British study compared attack rates for meningococcal C disease in children from infancy to age 18 before and 1 to 2 years after the institution of a nationwide meningococcal serogroup C conjugate vaccination. Vaccine coverage ranged from 66% (adolescents) to 87% (schoolchildren), and vaccine efficacy was 94% to 96%. Incidence of meningococcal C disease in the unvaccinated children also decreased by 52% to 67% (from 4.08/100,000 to 1.36/100,000).⁵

Vaccinating adolescents may be particularly helpful for building herd immunity. A Norwegian study of nasopharyngeal meningococcal carriage among 943 unimmunized individuals ages 2 months to 95 years found a carriage rate of 28% among 15- to 24-year-olds, compared with 9.6% overall.⁶

High hospitalization rates in US military recruits during 1964 to 1970 (25.2/100,000) led to the development of the meningococcal polysaccharide vaccine. Since 1971, all new military recruits have received polysaccharide meningococcal vaccine, and for the period 1990 to 1998 the hospitalization rate for meningococcal disease among active duty service members had decreased by 98% (to 0.51/100,000).⁷

Recommendations from others

The Advisory Committee on Immunization Practices,² American Academy of Pediatrics,⁸ American Academy of Family Physicians,⁹ and American College Association¹⁰ recommendations are summarized in the TABLE. Recommendations for vaccination during meningococcal disease outbreaks can be found at www.cdc.gov.²

TABLE

Who should get vaccinated—and when

Evidence summary

Two meningococcal vaccines are currently available in the US: tetravalent polysaccharide vaccine (MPSV4) and tetravalent polysaccharide-protein conjugate vaccine (MCV4). Both protect against serogroups A, C, Y, and W-135, but not against serogroup B, which is the most prevalent. A vaccine for serogroup B is under development.

MPSV4 is licensed for ages 2 years and up, but its poor immunogenicity in infants, lack of memory and booster response, and relatively short duration of protection have restricted its use. MCV4 is licensed for 11- to 55-year-olds and is the preferred vaccine in this age group, since it provides longer duration of immunity and reduces nasopharyngeal carriage.¹

Infants and freshman are especially vulnerable

Using active community surveillance from 1991 to 2002, Centers for Disease Control and Prevention (CDC) data² found annual rates of meningococcal disease in the US of 0.5 to 1.1 per 100,000. The highest rates were found in children under age 2. Infants younger than 12 months of age were especially vulnerable (rate 9/100,000), with more than 50% of cases caused by serogroup B.

A 1998–1999 prospective surveillance study³ including 50 state health departments and 231 college health centers identified 96 cases of meningococcal disease in college students (incidence 0.7/100,000). Freshmen living in dormitories had an elevated risk of meningococcal disease compared with other undergraduates or nonstudents of the same age (incidence 5.1/100,000; adjusted relative risk=3.6 [95% confidence interval [CI], 1.6–8.5). Sixty-eight percent had illness due to a vaccine-preventable serogroup.

Using CDC incidence data, a cost-effectiveness model⁴ compared hypothetical vaccination strategies targeting US infants (3 doses), toddlers (1 dose), or 11-year-olds (1 dose). Routine MCV4 vaccination of all 11-year-olds would prevent 270 cases and 36 deaths in this cohort over their next 22 years. For a toddler cohort, vaccination would prevent 385 cases and 33 deaths; for infants, 447 cases and 36 deaths. Conjugate meningococcal vaccines for serogroups A and C have been tested and used in children in other countries, and appear safe and effective, but are not yet available in the US. An application has been submitted for FDA approval of MCV4 for 2- to 10-year-olds.

Herd immunity may expand benefit of vaccination

A British study compared attack rates for meningococcal C disease in children from infancy to age 18 before and 1 to 2 years after the institution of a nationwide meningococcal serogroup C conjugate vaccination. Vaccine coverage ranged from 66% (adolescents) to 87% (schoolchildren), and vaccine efficacy was 94% to 96%. Incidence of meningococcal C disease in the unvaccinated children also decreased by 52% to 67% (from 4.08/100,000 to 1.36/100,000).⁵

Vaccinating adolescents may be particularly helpful for building herd immunity. A Norwegian study of nasopharyngeal meningococcal carriage among 943 unimmunized individuals ages 2 months to 95 years found a carriage rate of 28% among 15- to 24-year-olds, compared with 9.6% overall.⁶

High hospitalization rates in US military recruits during 1964 to 1970 (25.2/100,000) led to the development of the meningococcal polysaccharide vaccine. Since 1971, all new military recruits have received polysaccharide meningococcal vaccine, and for the period 1990 to 1998 the hospitalization rate for meningococcal disease among active duty service members had decreased by 98% (to 0.51/100,000).⁷

Recommendations from others

The Advisory Committee on Immunization Practices,² American Academy of Pediatrics,⁸ American Academy of Family Physicians,⁹ and American College Association¹⁰ recommendations are summarized in the TABLE. Recommendations for vaccination during meningococcal disease outbreaks can be found at www.cdc.gov.²

TABLE

Who should get vaccinated—and when

Evidence summary

Two meningococcal vaccines are currently available in the US: tetravalent polysaccharide vaccine (MPSV4) and tetravalent polysaccharide-protein conjugate vaccine (MCV4). Both protect against serogroups A, C, Y, and W-135, but not against serogroup B, which is the most prevalent. A vaccine for serogroup B is under development.

MPSV4 is licensed for ages 2 years and up, but its poor immunogenicity in infants, lack of memory and booster response, and relatively short duration of protection have restricted its use. MCV4 is licensed for 11- to 55-year-olds and is the preferred vaccine in this age group, since it provides longer duration of immunity and reduces nasopharyngeal carriage.¹

Infants and freshman are especially vulnerable

Using active community surveillance from 1991 to 2002, Centers for Disease Control and Prevention (CDC) data² found annual rates of meningococcal disease in the US of 0.5 to 1.1 per 100,000. The highest rates were found in children under age 2. Infants younger than 12 months of age were especially vulnerable (rate 9/100,000), with more than 50% of cases caused by serogroup B.

A 1998–1999 prospective surveillance study³ including 50 state health departments and 231 college health centers identified 96 cases of meningococcal disease in college students (incidence 0.7/100,000). Freshmen living in dormitories had an elevated risk of meningococcal disease compared with other undergraduates or nonstudents of the same age (incidence 5.1/100,000; adjusted relative risk=3.6 [95% confidence interval [CI], 1.6–8.5). Sixty-eight percent had illness due to a vaccine-preventable serogroup.

Using CDC incidence data, a cost-effectiveness model⁴ compared hypothetical vaccination strategies targeting US infants (3 doses), toddlers (1 dose), or 11-year-olds (1 dose). Routine MCV4 vaccination of all 11-year-olds would prevent 270 cases and 36 deaths in this cohort over their next 22 years. For a toddler cohort, vaccination would prevent 385 cases and 33 deaths; for infants, 447 cases and 36 deaths. Conjugate meningococcal vaccines for serogroups A and C have been tested and used in children in other countries, and appear safe and effective, but are not yet available in the US. An application has been submitted for FDA approval of MCV4 for 2- to 10-year-olds.

Herd immunity may expand benefit of vaccination

A British study compared attack rates for meningococcal C disease in children from infancy to age 18 before and 1 to 2 years after the institution of a nationwide meningococcal serogroup C conjugate vaccination. Vaccine coverage ranged from 66% (adolescents) to 87% (schoolchildren), and vaccine efficacy was 94% to 96%. Incidence of meningococcal C disease in the unvaccinated children also decreased by 52% to 67% (from 4.08/100,000 to 1.36/100,000).⁵

Vaccinating adolescents may be particularly helpful for building herd immunity. A Norwegian study of nasopharyngeal meningococcal carriage among 943 unimmunized individuals ages 2 months to 95 years found a carriage rate of 28% among 15- to 24-year-olds, compared with 9.6% overall.⁶

High hospitalization rates in US military recruits during 1964 to 1970 (25.2/100,000) led to the development of the meningococcal polysaccharide vaccine. Since 1971, all new military recruits have received polysaccharide meningococcal vaccine, and for the period 1990 to 1998 the hospitalization rate for meningococcal disease among active duty service members had decreased by 98% (to 0.51/100,000).⁷

Recommendations from others

The Advisory Committee on Immunization Practices,² American Academy of Pediatrics,⁸ American Academy of Family Physicians,⁹ and American College Association¹⁰ recommendations are summarized in the TABLE. Recommendations for vaccination during meningococcal disease outbreaks can be found at www.cdc.gov.²

TABLE

Who should get vaccinated—and when

Evidence summary

For acutely febrile patients, the presence of an elevated white blood cell (WBC) count with elevated band forms has dogmatically been thought of as a marker for bacterial infection.¹ Current literature, however, does not support this.²

Neisseria meningitides

A retrospective study of 5353 infants ages 3 to 89 days presenting to the emergency department for evaluation of fever showed that 3 of 4 infants ultimately diagnosed with bacterial meningitis would have been missed if the WBC count alone were used to predict which infants need a lumbar puncture.³ A prospective study of 2492 children ages 3 to 24 months presenting to the emergency department with acute fever and an absolute WBC count >15,000/mm³ revealed that neither a polymorphonuclear count of >10,000/mm³ (>66% segmented forms) nor a band count of >500/mm³ was associated with an increased likelihood of occult bacterial infection.⁴ Other studies show that the WBC alone is poorly discriminatory for identifying either bacteremia or meningitis.^5,6

To improve the diagnostic utility of the CBC, other studies have examined individual components of the white blood cell differential count (TABLE 1). In particular, the use of the absolute neutrophil count (ANC) has been proposed as a superior marker of serious bacterial infection.⁷ A review of 6579 outpatients aged 3 to 36 months presenting to the emergency department with temperatures of 39°C or higher showed an ANC of >10,000/mm³ as more predictive of occult pneumococcal bacteremia than an elevated WBC count (>15,000/mm³) alone.⁸ Another retrospective review of more than 10,000 patients aged 3 to 36 months presenting to the emergency department used logistic regression to identify predictors of bacteremia. In this study, ANC (>9500/mm³) and WBC (>14,300/mm³) were of equal sensitivity (75%) and specificity (75%) in identifying serious bacterial infection.⁹ Finally, the band count alone does not accurately predict serious bacterial infection.¹⁰

In summary, the CBC cannot be used in isolation to differentiate bacterial from viral illness. The CBC can, however, augment clinical data from the history and physical examination to predict the likelihood of serious bacterial illness. As a result, numerous diagnostic criteria, each incorporating elements of the CBC, have been developed in an attempt to accurately differentiate bacterial from viral illness in acutely febrile patients, most typically children (TABLE 2). These criteria differ by age of the patient, clinical testing recommendations, indications for antibiotic therapy, as well as WBC cutoffs.

TABLE 1
WBC markers: How good are they at predicting serious bacterial infection?^9,18,19

TABLE 2
Clinical criteria for predicting serious bacterial infection in febrile children

Recommendations from others

The American College of Emergency Physicians recommends considering antibiotic therapy for previously healthy, well-appearing children ages 3 to 36 months who present with a fever without a clinical source and a WBC count >15,000/mm³.^3,14

The University of Cincinnati Evidence-Based Clinical Practice Guidelines for fever of uncertain source in children ages 2 to 36 months recommends obtaining a CBC for any child who is ill-appearing or at high risk for bacteremia (determined by the clinicians’ judgment). A WBC of ≥15,000/mm³ or ANC >10,000/mm³ provide support for antibiotic therapy.¹⁵ The 1993 American Academy of Pediatrics guidelines for fever ≥39°C without a source in children ages 3 months to 3 years recommends a CBC; if the WBC count ≥15,000/mm³, they recommend a blood culture and treatment with antibiotics pending culture results.^3,16

It is important to note that in the age of Haemophilus influenza and Streptococcus pneumonia vaccination, the rate of occult bacteremia in febrile children presenting without a source has fallen from 3% to 10% to 1% or less.¹⁷ A lower prevalence reduces the utility of routine CBC or blood culture in the evaluation of immunized, febrile children. Parameters such as procalcitonin, interleukin-6, interleukin-8, interleukin-1 receptor antagonist and C-reactive protein show future promise as biochemical markers for identifying serious bacterial infections.¹⁸

Evidence summary

For acutely febrile patients, the presence of an elevated white blood cell (WBC) count with elevated band forms has dogmatically been thought of as a marker for bacterial infection.¹ Current literature, however, does not support this.²

Neisseria meningitides

A retrospective study of 5353 infants ages 3 to 89 days presenting to the emergency department for evaluation of fever showed that 3 of 4 infants ultimately diagnosed with bacterial meningitis would have been missed if the WBC count alone were used to predict which infants need a lumbar puncture.³ A prospective study of 2492 children ages 3 to 24 months presenting to the emergency department with acute fever and an absolute WBC count >15,000/mm³ revealed that neither a polymorphonuclear count of >10,000/mm³ (>66% segmented forms) nor a band count of >500/mm³ was associated with an increased likelihood of occult bacterial infection.⁴ Other studies show that the WBC alone is poorly discriminatory for identifying either bacteremia or meningitis.^5,6

To improve the diagnostic utility of the CBC, other studies have examined individual components of the white blood cell differential count (TABLE 1). In particular, the use of the absolute neutrophil count (ANC) has been proposed as a superior marker of serious bacterial infection.⁷ A review of 6579 outpatients aged 3 to 36 months presenting to the emergency department with temperatures of 39°C or higher showed an ANC of >10,000/mm³ as more predictive of occult pneumococcal bacteremia than an elevated WBC count (>15,000/mm³) alone.⁸ Another retrospective review of more than 10,000 patients aged 3 to 36 months presenting to the emergency department used logistic regression to identify predictors of bacteremia. In this study, ANC (>9500/mm³) and WBC (>14,300/mm³) were of equal sensitivity (75%) and specificity (75%) in identifying serious bacterial infection.⁹ Finally, the band count alone does not accurately predict serious bacterial infection.¹⁰

In summary, the CBC cannot be used in isolation to differentiate bacterial from viral illness. The CBC can, however, augment clinical data from the history and physical examination to predict the likelihood of serious bacterial illness. As a result, numerous diagnostic criteria, each incorporating elements of the CBC, have been developed in an attempt to accurately differentiate bacterial from viral illness in acutely febrile patients, most typically children (TABLE 2). These criteria differ by age of the patient, clinical testing recommendations, indications for antibiotic therapy, as well as WBC cutoffs.

TABLE 1
WBC markers: How good are they at predicting serious bacterial infection?^9,18,19

TABLE 2
Clinical criteria for predicting serious bacterial infection in febrile children

Recommendations from others

The American College of Emergency Physicians recommends considering antibiotic therapy for previously healthy, well-appearing children ages 3 to 36 months who present with a fever without a clinical source and a WBC count >15,000/mm³.^3,14

The University of Cincinnati Evidence-Based Clinical Practice Guidelines for fever of uncertain source in children ages 2 to 36 months recommends obtaining a CBC for any child who is ill-appearing or at high risk for bacteremia (determined by the clinicians’ judgment). A WBC of ≥15,000/mm³ or ANC >10,000/mm³ provide support for antibiotic therapy.¹⁵ The 1993 American Academy of Pediatrics guidelines for fever ≥39°C without a source in children ages 3 months to 3 years recommends a CBC; if the WBC count ≥15,000/mm³, they recommend a blood culture and treatment with antibiotics pending culture results.^3,16

It is important to note that in the age of Haemophilus influenza and Streptococcus pneumonia vaccination, the rate of occult bacteremia in febrile children presenting without a source has fallen from 3% to 10% to 1% or less.¹⁷ A lower prevalence reduces the utility of routine CBC or blood culture in the evaluation of immunized, febrile children. Parameters such as procalcitonin, interleukin-6, interleukin-8, interleukin-1 receptor antagonist and C-reactive protein show future promise as biochemical markers for identifying serious bacterial infections.¹⁸

Evidence summary

For acutely febrile patients, the presence of an elevated white blood cell (WBC) count with elevated band forms has dogmatically been thought of as a marker for bacterial infection.¹ Current literature, however, does not support this.²

Neisseria meningitides

A retrospective study of 5353 infants ages 3 to 89 days presenting to the emergency department for evaluation of fever showed that 3 of 4 infants ultimately diagnosed with bacterial meningitis would have been missed if the WBC count alone were used to predict which infants need a lumbar puncture.³ A prospective study of 2492 children ages 3 to 24 months presenting to the emergency department with acute fever and an absolute WBC count >15,000/mm³ revealed that neither a polymorphonuclear count of >10,000/mm³ (>66% segmented forms) nor a band count of >500/mm³ was associated with an increased likelihood of occult bacterial infection.⁴ Other studies show that the WBC alone is poorly discriminatory for identifying either bacteremia or meningitis.^5,6

To improve the diagnostic utility of the CBC, other studies have examined individual components of the white blood cell differential count (TABLE 1). In particular, the use of the absolute neutrophil count (ANC) has been proposed as a superior marker of serious bacterial infection.⁷ A review of 6579 outpatients aged 3 to 36 months presenting to the emergency department with temperatures of 39°C or higher showed an ANC of >10,000/mm³ as more predictive of occult pneumococcal bacteremia than an elevated WBC count (>15,000/mm³) alone.⁸ Another retrospective review of more than 10,000 patients aged 3 to 36 months presenting to the emergency department used logistic regression to identify predictors of bacteremia. In this study, ANC (>9500/mm³) and WBC (>14,300/mm³) were of equal sensitivity (75%) and specificity (75%) in identifying serious bacterial infection.⁹ Finally, the band count alone does not accurately predict serious bacterial infection.¹⁰

In summary, the CBC cannot be used in isolation to differentiate bacterial from viral illness. The CBC can, however, augment clinical data from the history and physical examination to predict the likelihood of serious bacterial illness. As a result, numerous diagnostic criteria, each incorporating elements of the CBC, have been developed in an attempt to accurately differentiate bacterial from viral illness in acutely febrile patients, most typically children (TABLE 2). These criteria differ by age of the patient, clinical testing recommendations, indications for antibiotic therapy, as well as WBC cutoffs.

TABLE 1
WBC markers: How good are they at predicting serious bacterial infection?^9,18,19

TABLE 2
Clinical criteria for predicting serious bacterial infection in febrile children

Recommendations from others

The American College of Emergency Physicians recommends considering antibiotic therapy for previously healthy, well-appearing children ages 3 to 36 months who present with a fever without a clinical source and a WBC count >15,000/mm³.^3,14

The University of Cincinnati Evidence-Based Clinical Practice Guidelines for fever of uncertain source in children ages 2 to 36 months recommends obtaining a CBC for any child who is ill-appearing or at high risk for bacteremia (determined by the clinicians’ judgment). A WBC of ≥15,000/mm³ or ANC >10,000/mm³ provide support for antibiotic therapy.¹⁵ The 1993 American Academy of Pediatrics guidelines for fever ≥39°C without a source in children ages 3 months to 3 years recommends a CBC; if the WBC count ≥15,000/mm³, they recommend a blood culture and treatment with antibiotics pending culture results.^3,16

It is important to note that in the age of Haemophilus influenza and Streptococcus pneumonia vaccination, the rate of occult bacteremia in febrile children presenting without a source has fallen from 3% to 10% to 1% or less.¹⁷ A lower prevalence reduces the utility of routine CBC or blood culture in the evaluation of immunized, febrile children. Parameters such as procalcitonin, interleukin-6, interleukin-8, interleukin-1 receptor antagonist and C-reactive protein show future promise as biochemical markers for identifying serious bacterial infections.¹⁸

Evidence summary

Our search identified no randomized controlled trials, no systematic reviews, 6 observational studies, and 3 consensus panel guidelines on risks from driving and cardiovascular disease. No studies deal specifically with coronary artery disease, congestive heart failure, or valvular heart disease and the risk of motor vehicle crashes for patients with these conditions. A population-based case control study of 5204 male drivers ages 45 to 70 in Quebec found no increased risk of crash for drivers with unspecified cardiovascular disease.¹

Car accidents among ICD patients are low

The most studied patients are those with life-threatening ventricular arrhythmias—particularly those with implantable cardioverter-defibrillators (ICDs). Based on observational studies of patients and their physicians, patients with ventricular arrhythmias treated with ICDs do not have an increased risk of motor vehicle crashes.^2-4 The largest of the studies² prospectively and anonymously surveyed 627 patients from the Antiarrhythmics vs Implantable Defibrillators Trial. During follow-up, 2% of patients had a syncopal episode while driving, and 11% had dizziness or palpitations that required stopping the vehicle.

Of the 55 car crashes that occurred during 1619 patient-years after resumption of driving, 11% were preceded by a possible symptom of arrhythmia (0.4% per patient per year). The annual incidence of car accidents for patients with an ICD was 3.4% per patient-year. This is substantially lower than the 7.1% rate among the general driving population in the US.

Recommendations from others

Expert panel guidelines regarding fitness to drive for patients with heart disease are available from the Canadian Cardiovascular Society (CCS),⁵ the European Society of Cardiology, the American Heart Association, the North American Society of Pacing and Physiology,⁶ and the Cardiac Society of Australia and New Zealand.⁷ The 2004 CCS guidelines are the most recent and include a “Risk of Harm” formula that attempts to assign a quantitative level of risk to drivers with heart disease. These guidelines appear sensible but are not evidence-based (TABLE).

TABLE
Should your heart patient get behind the wheel? A helpful guide

Evidence summary

Our search identified no randomized controlled trials, no systematic reviews, 6 observational studies, and 3 consensus panel guidelines on risks from driving and cardiovascular disease. No studies deal specifically with coronary artery disease, congestive heart failure, or valvular heart disease and the risk of motor vehicle crashes for patients with these conditions. A population-based case control study of 5204 male drivers ages 45 to 70 in Quebec found no increased risk of crash for drivers with unspecified cardiovascular disease.¹

Car accidents among ICD patients are low

The most studied patients are those with life-threatening ventricular arrhythmias—particularly those with implantable cardioverter-defibrillators (ICDs). Based on observational studies of patients and their physicians, patients with ventricular arrhythmias treated with ICDs do not have an increased risk of motor vehicle crashes.^2-4 The largest of the studies² prospectively and anonymously surveyed 627 patients from the Antiarrhythmics vs Implantable Defibrillators Trial. During follow-up, 2% of patients had a syncopal episode while driving, and 11% had dizziness or palpitations that required stopping the vehicle.

Of the 55 car crashes that occurred during 1619 patient-years after resumption of driving, 11% were preceded by a possible symptom of arrhythmia (0.4% per patient per year). The annual incidence of car accidents for patients with an ICD was 3.4% per patient-year. This is substantially lower than the 7.1% rate among the general driving population in the US.

Recommendations from others

Expert panel guidelines regarding fitness to drive for patients with heart disease are available from the Canadian Cardiovascular Society (CCS),⁵ the European Society of Cardiology, the American Heart Association, the North American Society of Pacing and Physiology,⁶ and the Cardiac Society of Australia and New Zealand.⁷ The 2004 CCS guidelines are the most recent and include a “Risk of Harm” formula that attempts to assign a quantitative level of risk to drivers with heart disease. These guidelines appear sensible but are not evidence-based (TABLE).

TABLE
Should your heart patient get behind the wheel? A helpful guide

Evidence summary

Our search identified no randomized controlled trials, no systematic reviews, 6 observational studies, and 3 consensus panel guidelines on risks from driving and cardiovascular disease. No studies deal specifically with coronary artery disease, congestive heart failure, or valvular heart disease and the risk of motor vehicle crashes for patients with these conditions. A population-based case control study of 5204 male drivers ages 45 to 70 in Quebec found no increased risk of crash for drivers with unspecified cardiovascular disease.¹

Car accidents among ICD patients are low

The most studied patients are those with life-threatening ventricular arrhythmias—particularly those with implantable cardioverter-defibrillators (ICDs). Based on observational studies of patients and their physicians, patients with ventricular arrhythmias treated with ICDs do not have an increased risk of motor vehicle crashes.^2-4 The largest of the studies² prospectively and anonymously surveyed 627 patients from the Antiarrhythmics vs Implantable Defibrillators Trial. During follow-up, 2% of patients had a syncopal episode while driving, and 11% had dizziness or palpitations that required stopping the vehicle.

Of the 55 car crashes that occurred during 1619 patient-years after resumption of driving, 11% were preceded by a possible symptom of arrhythmia (0.4% per patient per year). The annual incidence of car accidents for patients with an ICD was 3.4% per patient-year. This is substantially lower than the 7.1% rate among the general driving population in the US.

Recommendations from others

Expert panel guidelines regarding fitness to drive for patients with heart disease are available from the Canadian Cardiovascular Society (CCS),⁵ the European Society of Cardiology, the American Heart Association, the North American Society of Pacing and Physiology,⁶ and the Cardiac Society of Australia and New Zealand.⁷ The 2004 CCS guidelines are the most recent and include a “Risk of Harm” formula that attempts to assign a quantitative level of risk to drivers with heart disease. These guidelines appear sensible but are not evidence-based (TABLE).

TABLE
Should your heart patient get behind the wheel? A helpful guide

Evidence summary

Experts advise screening all children for obstructive sleep apnea by asking about snoring and sleep apnea at routine health supervision visits.¹ Obstructive sleep apnea among children has an overall prevalence of 2% but occurs in approximately 13% to 25% of those who snore regularly and heavily.^1,2

Obstructive sleep apnea is unlikely in the absence of habitual snoring (expert opinion), and snoring loudness does not correlate with severity. Children with obstructive sleep apnea tend to exhibit symptoms typical of attention-deficit and hyperactivity disorder rather than daytime somnolence.²

Adenotonsillar hypertrophy may be to blame

The most common cause of obstructive sleep apnea is adenotonsillar hypertrophy. Additional risk factors include obesity, allergic rhinitis, neuromuscular disease, craniofacial anomalies, Down syndrome, premature birth, and family history.¹

A prospective case-series of 62 consecutive children referred to a sleep clinic for suspected obstructive sleep apnea correlated nightly snoring (relative risk [RR]=10.67; 95% confidence interval [CI], 2.72–41.8) and observed apnea (RR=3.43; 95% CI, 1.42–6.76) with obstructive sleep apnea diagnosed by polysomnography.³ Children with underlying neurological or craniofacial problems were excluded. A retrospective, nonconsecutive cohort study of 50 children previously diagnosed with obstructive sleep apnea found that all presented with “continuous heavy snoring, interrupted by pauses and associated with snorts.”⁴

Don’t count on the physical exam and history

Experts consider overnight polysomnography to be the gold standard test for obstructive sleep apnea.² Physical examination alone usually has normal results. A systematic review of 12 studies including 1058 children under age 18 compared evaluation by polysomnography with clinical evaluation by history and physical examination alone. Clinical evaluation had a positive predictive value (PPV) of 55.8% (95% CI, 42.1%–69.6%); no single component demonstrated sensitivity and specificity more than 65%.⁵

Symptom questionnaires or scales did not correlate well with polysomnography results in 3 studies (which excluded children with craniofacial anomalies, significant medical problems, or prior upper airway surgery). The best study—a prospective, randomized, investigator-blinded, controlled trial of 59 consecutive children clinically diagnosed with obstructive sleep apnea—compared a “clinical assessment score” (comprised of standardized history, physical exam, voice recording, sleep audio recording, lateral neck radiograph, and echocardiogram) with overnight polysomnography. The majority of children had mild obstructive sleep apnea. Overall, the clinical assessment score did not correlate well with polysomnography (PPV=48%).⁶

Avoid sequential and abbreviated tests

Sequential overnight polysomnography did not dramatically improve sensitivity or specificity over a single test in 2 prospective studies of children with suspected obstructive sleep apnea. The larger study recruited 70 consecutive children (ages 2 to 17 years) from a sleep lab and performed polysomnography on 2 consecutive nights. The first test correctly identified obstructive sleep apnea in 64 children; the second identified 6 additional cases, all of which were “mild.”⁷

Abbreviated polysomnographies have inadequate sensitivity. A retrospective chart review included 143 children between 1 and 18 years of age with adenotonsillar hypertrophy referred for overnight polysomnography after normal or mildly abnormal “nap polysomnography.” Mildly abnormal nap polysomnography predicted abnormal overnight polysomnography (PPV=77%; P<.0001), but normal nap polysomnography were not predictive of normal overnight polysomnography (NPV=49%; P=.8).⁸

Video recordings have low specificity

A prospective cohort study of home sleep video recordings included 58 consecutive children who were 2 to 6 years of age with snoring or labored breathing during sleep. Parents filmed 30 minutes of sleep during “worst breathing” episodes. An expert investigator evaluated the recordings using both a standardized scoring system and subjective impression, and compared these with overnight polysomnography results, finding 94% sensitivity and 68% specificity.⁹

Two prospective trials compared standardized scoring of home sleep audio recordings with overnight polysomnography testing. The best study, an investigator-blinded RCT, scored 20-minute recordings of “worst breathing” in 59 consecutive children referred for snoring or nocturnal breathing problems, 47% of whom had sleep apnea. Results: PPV=62%, NPV=83%, sensitivity=88%, specificity=52%.⁷

Abnormal pulse ox is highly predictive

A retrospective, cross-sectional study of 349 children between the ages of 6 months and 18 years determined that abnormal home pulse oximetry studies were highly predictive of obstructive sleep apnea on polysomnography (positive likelihood ratio [LR+]=19.4; CIs not given; posttest probability=97%), but that inconclusive or normal pulse oximetry studies were not predictive of negative polysomnographies (LR+=0.58; CIs not given; posttest probability 47%). Children had been referred for suspected obstructive sleep apnea, and the pretest probability was 60%. Oximetry records were evaluated by a sleep laboratory physician blinded to clinical and polysomnography data.¹⁰

Tonsillar-pharyngeal ratio misses mild cases

A prospective cohort study of 35 children compared the tonsillar-pharyngeal ratio measured from lateral neck x-rays to overnight polysomnography. X-ray measurements predicted moderate or severe obstructive sleep apnea on polysomnography (sensitivity=96%, specificity=82%, PPV=92%, NPV=90%), but did not accurately differentiate normal children from those with mild obstructive sleep apnea.¹¹

Recommendations from others

The American Academy of Pediatrics recommends that children be screened during well child visits for regular snoring or apnea episodes during sleep. Children with positive screens should have an overnight polysomnography. Children with confirmed obstructive sleep apnea should be referred to a sleep medicine specialist to consider continuous positive airway pressure therapy during sleep, or to an otolaryngologist for possible surgery (tonsillectomy or adenoidectomy).²

Evidence summary

Experts advise screening all children for obstructive sleep apnea by asking about snoring and sleep apnea at routine health supervision visits.¹ Obstructive sleep apnea among children has an overall prevalence of 2% but occurs in approximately 13% to 25% of those who snore regularly and heavily.^1,2

Obstructive sleep apnea is unlikely in the absence of habitual snoring (expert opinion), and snoring loudness does not correlate with severity. Children with obstructive sleep apnea tend to exhibit symptoms typical of attention-deficit and hyperactivity disorder rather than daytime somnolence.²

Adenotonsillar hypertrophy may be to blame

The most common cause of obstructive sleep apnea is adenotonsillar hypertrophy. Additional risk factors include obesity, allergic rhinitis, neuromuscular disease, craniofacial anomalies, Down syndrome, premature birth, and family history.¹

A prospective case-series of 62 consecutive children referred to a sleep clinic for suspected obstructive sleep apnea correlated nightly snoring (relative risk [RR]=10.67; 95% confidence interval [CI], 2.72–41.8) and observed apnea (RR=3.43; 95% CI, 1.42–6.76) with obstructive sleep apnea diagnosed by polysomnography.³ Children with underlying neurological or craniofacial problems were excluded. A retrospective, nonconsecutive cohort study of 50 children previously diagnosed with obstructive sleep apnea found that all presented with “continuous heavy snoring, interrupted by pauses and associated with snorts.”⁴

Don’t count on the physical exam and history

Experts consider overnight polysomnography to be the gold standard test for obstructive sleep apnea.² Physical examination alone usually has normal results. A systematic review of 12 studies including 1058 children under age 18 compared evaluation by polysomnography with clinical evaluation by history and physical examination alone. Clinical evaluation had a positive predictive value (PPV) of 55.8% (95% CI, 42.1%–69.6%); no single component demonstrated sensitivity and specificity more than 65%.⁵

Symptom questionnaires or scales did not correlate well with polysomnography results in 3 studies (which excluded children with craniofacial anomalies, significant medical problems, or prior upper airway surgery). The best study—a prospective, randomized, investigator-blinded, controlled trial of 59 consecutive children clinically diagnosed with obstructive sleep apnea—compared a “clinical assessment score” (comprised of standardized history, physical exam, voice recording, sleep audio recording, lateral neck radiograph, and echocardiogram) with overnight polysomnography. The majority of children had mild obstructive sleep apnea. Overall, the clinical assessment score did not correlate well with polysomnography (PPV=48%).⁶

Avoid sequential and abbreviated tests

Sequential overnight polysomnography did not dramatically improve sensitivity or specificity over a single test in 2 prospective studies of children with suspected obstructive sleep apnea. The larger study recruited 70 consecutive children (ages 2 to 17 years) from a sleep lab and performed polysomnography on 2 consecutive nights. The first test correctly identified obstructive sleep apnea in 64 children; the second identified 6 additional cases, all of which were “mild.”⁷

Abbreviated polysomnographies have inadequate sensitivity. A retrospective chart review included 143 children between 1 and 18 years of age with adenotonsillar hypertrophy referred for overnight polysomnography after normal or mildly abnormal “nap polysomnography.” Mildly abnormal nap polysomnography predicted abnormal overnight polysomnography (PPV=77%; P<.0001), but normal nap polysomnography were not predictive of normal overnight polysomnography (NPV=49%; P=.8).⁸

Video recordings have low specificity

A prospective cohort study of home sleep video recordings included 58 consecutive children who were 2 to 6 years of age with snoring or labored breathing during sleep. Parents filmed 30 minutes of sleep during “worst breathing” episodes. An expert investigator evaluated the recordings using both a standardized scoring system and subjective impression, and compared these with overnight polysomnography results, finding 94% sensitivity and 68% specificity.⁹

Two prospective trials compared standardized scoring of home sleep audio recordings with overnight polysomnography testing. The best study, an investigator-blinded RCT, scored 20-minute recordings of “worst breathing” in 59 consecutive children referred for snoring or nocturnal breathing problems, 47% of whom had sleep apnea. Results: PPV=62%, NPV=83%, sensitivity=88%, specificity=52%.⁷

Abnormal pulse ox is highly predictive

A retrospective, cross-sectional study of 349 children between the ages of 6 months and 18 years determined that abnormal home pulse oximetry studies were highly predictive of obstructive sleep apnea on polysomnography (positive likelihood ratio [LR+]=19.4; CIs not given; posttest probability=97%), but that inconclusive or normal pulse oximetry studies were not predictive of negative polysomnographies (LR+=0.58; CIs not given; posttest probability 47%). Children had been referred for suspected obstructive sleep apnea, and the pretest probability was 60%. Oximetry records were evaluated by a sleep laboratory physician blinded to clinical and polysomnography data.¹⁰

Tonsillar-pharyngeal ratio misses mild cases

A prospective cohort study of 35 children compared the tonsillar-pharyngeal ratio measured from lateral neck x-rays to overnight polysomnography. X-ray measurements predicted moderate or severe obstructive sleep apnea on polysomnography (sensitivity=96%, specificity=82%, PPV=92%, NPV=90%), but did not accurately differentiate normal children from those with mild obstructive sleep apnea.¹¹

Recommendations from others

The American Academy of Pediatrics recommends that children be screened during well child visits for regular snoring or apnea episodes during sleep. Children with positive screens should have an overnight polysomnography. Children with confirmed obstructive sleep apnea should be referred to a sleep medicine specialist to consider continuous positive airway pressure therapy during sleep, or to an otolaryngologist for possible surgery (tonsillectomy or adenoidectomy).²

Evidence summary

Experts advise screening all children for obstructive sleep apnea by asking about snoring and sleep apnea at routine health supervision visits.¹ Obstructive sleep apnea among children has an overall prevalence of 2% but occurs in approximately 13% to 25% of those who snore regularly and heavily.^1,2

Obstructive sleep apnea is unlikely in the absence of habitual snoring (expert opinion), and snoring loudness does not correlate with severity. Children with obstructive sleep apnea tend to exhibit symptoms typical of attention-deficit and hyperactivity disorder rather than daytime somnolence.²

Adenotonsillar hypertrophy may be to blame

The most common cause of obstructive sleep apnea is adenotonsillar hypertrophy. Additional risk factors include obesity, allergic rhinitis, neuromuscular disease, craniofacial anomalies, Down syndrome, premature birth, and family history.¹

A prospective case-series of 62 consecutive children referred to a sleep clinic for suspected obstructive sleep apnea correlated nightly snoring (relative risk [RR]=10.67; 95% confidence interval [CI], 2.72–41.8) and observed apnea (RR=3.43; 95% CI, 1.42–6.76) with obstructive sleep apnea diagnosed by polysomnography.³ Children with underlying neurological or craniofacial problems were excluded. A retrospective, nonconsecutive cohort study of 50 children previously diagnosed with obstructive sleep apnea found that all presented with “continuous heavy snoring, interrupted by pauses and associated with snorts.”⁴

Don’t count on the physical exam and history

Experts consider overnight polysomnography to be the gold standard test for obstructive sleep apnea.² Physical examination alone usually has normal results. A systematic review of 12 studies including 1058 children under age 18 compared evaluation by polysomnography with clinical evaluation by history and physical examination alone. Clinical evaluation had a positive predictive value (PPV) of 55.8% (95% CI, 42.1%–69.6%); no single component demonstrated sensitivity and specificity more than 65%.⁵

Symptom questionnaires or scales did not correlate well with polysomnography results in 3 studies (which excluded children with craniofacial anomalies, significant medical problems, or prior upper airway surgery). The best study—a prospective, randomized, investigator-blinded, controlled trial of 59 consecutive children clinically diagnosed with obstructive sleep apnea—compared a “clinical assessment score” (comprised of standardized history, physical exam, voice recording, sleep audio recording, lateral neck radiograph, and echocardiogram) with overnight polysomnography. The majority of children had mild obstructive sleep apnea. Overall, the clinical assessment score did not correlate well with polysomnography (PPV=48%).⁶

Avoid sequential and abbreviated tests

Sequential overnight polysomnography did not dramatically improve sensitivity or specificity over a single test in 2 prospective studies of children with suspected obstructive sleep apnea. The larger study recruited 70 consecutive children (ages 2 to 17 years) from a sleep lab and performed polysomnography on 2 consecutive nights. The first test correctly identified obstructive sleep apnea in 64 children; the second identified 6 additional cases, all of which were “mild.”⁷

Abbreviated polysomnographies have inadequate sensitivity. A retrospective chart review included 143 children between 1 and 18 years of age with adenotonsillar hypertrophy referred for overnight polysomnography after normal or mildly abnormal “nap polysomnography.” Mildly abnormal nap polysomnography predicted abnormal overnight polysomnography (PPV=77%; P<.0001), but normal nap polysomnography were not predictive of normal overnight polysomnography (NPV=49%; P=.8).⁸

Video recordings have low specificity

A prospective cohort study of home sleep video recordings included 58 consecutive children who were 2 to 6 years of age with snoring or labored breathing during sleep. Parents filmed 30 minutes of sleep during “worst breathing” episodes. An expert investigator evaluated the recordings using both a standardized scoring system and subjective impression, and compared these with overnight polysomnography results, finding 94% sensitivity and 68% specificity.⁹

Two prospective trials compared standardized scoring of home sleep audio recordings with overnight polysomnography testing. The best study, an investigator-blinded RCT, scored 20-minute recordings of “worst breathing” in 59 consecutive children referred for snoring or nocturnal breathing problems, 47% of whom had sleep apnea. Results: PPV=62%, NPV=83%, sensitivity=88%, specificity=52%.⁷

Abnormal pulse ox is highly predictive

A retrospective, cross-sectional study of 349 children between the ages of 6 months and 18 years determined that abnormal home pulse oximetry studies were highly predictive of obstructive sleep apnea on polysomnography (positive likelihood ratio [LR+]=19.4; CIs not given; posttest probability=97%), but that inconclusive or normal pulse oximetry studies were not predictive of negative polysomnographies (LR+=0.58; CIs not given; posttest probability 47%). Children had been referred for suspected obstructive sleep apnea, and the pretest probability was 60%. Oximetry records were evaluated by a sleep laboratory physician blinded to clinical and polysomnography data.¹⁰

Tonsillar-pharyngeal ratio misses mild cases

A prospective cohort study of 35 children compared the tonsillar-pharyngeal ratio measured from lateral neck x-rays to overnight polysomnography. X-ray measurements predicted moderate or severe obstructive sleep apnea on polysomnography (sensitivity=96%, specificity=82%, PPV=92%, NPV=90%), but did not accurately differentiate normal children from those with mild obstructive sleep apnea.¹¹

Recommendations from others

The American Academy of Pediatrics recommends that children be screened during well child visits for regular snoring or apnea episodes during sleep. Children with positive screens should have an overnight polysomnography. Children with confirmed obstructive sleep apnea should be referred to a sleep medicine specialist to consider continuous positive airway pressure therapy during sleep, or to an otolaryngologist for possible surgery (tonsillectomy or adenoidectomy).²