Clinical Inquiries

Evidence summary

Desmopressin is an analogue of the natural pituitary hormone vasopressin acetate. It produces an antidiuretic effect, resulting in increased reabsorption of water from the kidney, a reduced volume of more concentrated urine entering the bladder, and a reduced 24-hour urine production.^1,2 Desmopressin is available in a nasal spray (10 μg/spray) and an oral tablet (0.2 mg), and is most often prescribed as 1 to 2 sprays per nostril or 1 to 3 tablets at bedtime, regardless of age or weight.¹

A Cochrane review¹ of 16 randomized controlled trials found nasal desmopressin to be better than placebo in reducing the number of wet nights per week (mean 1.34 fewer wet nights/week; 95% confidence interval, 1.11–1.57). Desmopressin at doses of 20 μg, 40 μg, and 60 μg similarly increased the likelihood of a cure (14 consecutive dry nights during treatment) in 3 trials reporting this outcome (relative risk for failure to achieve 14 dry nights with 20 μg=0.84; NNT for cure=5.6).³ No difference was found in cure rates after treatment was stopped. Data were insufficient to judge the effectiveness of the oral versus nasal route of desmopressin.¹

One randomized controlled trial found a linear dose response for oral desmopressin in reducing wet nights. After 2 weeks of treatment, the number of wet nights was decreased by 27%, 30%, and 40% at doses of 0.2 mg, 0.4 mg, and 0.6 mg, respectively, compared with 10% with placebo.¹

Snajderova and colleagues studied desmopressin as a long-term treatment for 55 children with primary nocturnal enuresis. Intranasal desmopressin was titrated upward until bedwetting stopped (7–21 μg; 89.1% responders); children in whom no response occurred to a maximum of 28 μg were excluded. Every 3 months, a weaning attempt was made; if relapse occurred, the previous successful dose was reinstated. At the end of each of the 3 years, the number of responders remained higher (72.7%, 70.9%, 61.6%) than the spontaneous cure rate of 15%.⁴

The Swedish Enuresis Trial (SWEET) demonstrated a similar outcome in an open-label study of 399 children.⁵

The main side effects of desmopressin are nasal discomfort, nose bleeds, headache, abdominal pain, rash, and (rare but serious) water intoxication. Restrict fluid to 240 mL (8 oz) on nights desmopressin is given.¹

Recommendations from others

A University of California at San Diego Medical Group Guideline recommends using desmopressin for primary nocturnal enuresis in children aged >5 years when it occurs frequently and causes distress, as well as under specific circumstances, such as when a child shares a room or goes to camp, or a sleepover.

Therapy begins at 10 μg (1 nasal puff) each night, increasing weekly to a maximum of 40 μg. Younger children should be reassured, encouraged to limit fluids and void before bedtime, partake in the responsibility to change bedding, and be praised for dry nights.⁶

The American Academy of Pediatrics also emphasizes support and encouragement of the child, and reassurance that the problem will get better in time. For children aged 7 years, alarm systems or bladder-stretching exercises might help.⁷

Evidence summary

Desmopressin is an analogue of the natural pituitary hormone vasopressin acetate. It produces an antidiuretic effect, resulting in increased reabsorption of water from the kidney, a reduced volume of more concentrated urine entering the bladder, and a reduced 24-hour urine production.^1,2 Desmopressin is available in a nasal spray (10 μg/spray) and an oral tablet (0.2 mg), and is most often prescribed as 1 to 2 sprays per nostril or 1 to 3 tablets at bedtime, regardless of age or weight.¹

A Cochrane review¹ of 16 randomized controlled trials found nasal desmopressin to be better than placebo in reducing the number of wet nights per week (mean 1.34 fewer wet nights/week; 95% confidence interval, 1.11–1.57). Desmopressin at doses of 20 μg, 40 μg, and 60 μg similarly increased the likelihood of a cure (14 consecutive dry nights during treatment) in 3 trials reporting this outcome (relative risk for failure to achieve 14 dry nights with 20 μg=0.84; NNT for cure=5.6).³ No difference was found in cure rates after treatment was stopped. Data were insufficient to judge the effectiveness of the oral versus nasal route of desmopressin.¹

One randomized controlled trial found a linear dose response for oral desmopressin in reducing wet nights. After 2 weeks of treatment, the number of wet nights was decreased by 27%, 30%, and 40% at doses of 0.2 mg, 0.4 mg, and 0.6 mg, respectively, compared with 10% with placebo.¹

Snajderova and colleagues studied desmopressin as a long-term treatment for 55 children with primary nocturnal enuresis. Intranasal desmopressin was titrated upward until bedwetting stopped (7–21 μg; 89.1% responders); children in whom no response occurred to a maximum of 28 μg were excluded. Every 3 months, a weaning attempt was made; if relapse occurred, the previous successful dose was reinstated. At the end of each of the 3 years, the number of responders remained higher (72.7%, 70.9%, 61.6%) than the spontaneous cure rate of 15%.⁴

The Swedish Enuresis Trial (SWEET) demonstrated a similar outcome in an open-label study of 399 children.⁵

The main side effects of desmopressin are nasal discomfort, nose bleeds, headache, abdominal pain, rash, and (rare but serious) water intoxication. Restrict fluid to 240 mL (8 oz) on nights desmopressin is given.¹

Recommendations from others

A University of California at San Diego Medical Group Guideline recommends using desmopressin for primary nocturnal enuresis in children aged >5 years when it occurs frequently and causes distress, as well as under specific circumstances, such as when a child shares a room or goes to camp, or a sleepover.

Therapy begins at 10 μg (1 nasal puff) each night, increasing weekly to a maximum of 40 μg. Younger children should be reassured, encouraged to limit fluids and void before bedtime, partake in the responsibility to change bedding, and be praised for dry nights.⁶

The American Academy of Pediatrics also emphasizes support and encouragement of the child, and reassurance that the problem will get better in time. For children aged 7 years, alarm systems or bladder-stretching exercises might help.⁷

Evidence summary

Desmopressin is an analogue of the natural pituitary hormone vasopressin acetate. It produces an antidiuretic effect, resulting in increased reabsorption of water from the kidney, a reduced volume of more concentrated urine entering the bladder, and a reduced 24-hour urine production.^1,2 Desmopressin is available in a nasal spray (10 μg/spray) and an oral tablet (0.2 mg), and is most often prescribed as 1 to 2 sprays per nostril or 1 to 3 tablets at bedtime, regardless of age or weight.¹

A Cochrane review¹ of 16 randomized controlled trials found nasal desmopressin to be better than placebo in reducing the number of wet nights per week (mean 1.34 fewer wet nights/week; 95% confidence interval, 1.11–1.57). Desmopressin at doses of 20 μg, 40 μg, and 60 μg similarly increased the likelihood of a cure (14 consecutive dry nights during treatment) in 3 trials reporting this outcome (relative risk for failure to achieve 14 dry nights with 20 μg=0.84; NNT for cure=5.6).³ No difference was found in cure rates after treatment was stopped. Data were insufficient to judge the effectiveness of the oral versus nasal route of desmopressin.¹

One randomized controlled trial found a linear dose response for oral desmopressin in reducing wet nights. After 2 weeks of treatment, the number of wet nights was decreased by 27%, 30%, and 40% at doses of 0.2 mg, 0.4 mg, and 0.6 mg, respectively, compared with 10% with placebo.¹

Snajderova and colleagues studied desmopressin as a long-term treatment for 55 children with primary nocturnal enuresis. Intranasal desmopressin was titrated upward until bedwetting stopped (7–21 μg; 89.1% responders); children in whom no response occurred to a maximum of 28 μg were excluded. Every 3 months, a weaning attempt was made; if relapse occurred, the previous successful dose was reinstated. At the end of each of the 3 years, the number of responders remained higher (72.7%, 70.9%, 61.6%) than the spontaneous cure rate of 15%.⁴

The Swedish Enuresis Trial (SWEET) demonstrated a similar outcome in an open-label study of 399 children.⁵

The main side effects of desmopressin are nasal discomfort, nose bleeds, headache, abdominal pain, rash, and (rare but serious) water intoxication. Restrict fluid to 240 mL (8 oz) on nights desmopressin is given.¹

Recommendations from others

A University of California at San Diego Medical Group Guideline recommends using desmopressin for primary nocturnal enuresis in children aged >5 years when it occurs frequently and causes distress, as well as under specific circumstances, such as when a child shares a room or goes to camp, or a sleepover.

Therapy begins at 10 μg (1 nasal puff) each night, increasing weekly to a maximum of 40 μg. Younger children should be reassured, encouraged to limit fluids and void before bedtime, partake in the responsibility to change bedding, and be praised for dry nights.⁶

The American Academy of Pediatrics also emphasizes support and encouragement of the child, and reassurance that the problem will get better in time. For children aged 7 years, alarm systems or bladder-stretching exercises might help.⁷

Evidence summary

Three recent evidence-based guidelines^3,4,5 suggest that children and adults with acute sinusitis may benefit from treatment with antibiotics more than those with rhinitis. Clinicians must develop a strategy for accurately diagnosing sinusitis to make sound treatment decisions. In the absence of a clear diagnosis of acute sinusitis, antibiotics are very unlikely to improve symptoms and are, therefore, not indicated.

Clinical evaluation. Berg¹ studied 150 patients with clinical diagnoses of sinusitis and found that 85% of them had positive sinus puncture. In a review of the 11 studies that met evidence-based inclusion criteria, Varonen⁶ concluded that clinical evaluation has a sensitivity of roughly 0.75, whereas radiographic methodologies have sensitivities >0.80. In a prospective trial and subsequent review of the literature, Lindbaek^7,8,9 suggests that several key clinical signs and symptoms can provide a level of sensitivity that approaches that of CT or magnetic resonance imaging (MRI), while enhancing specificity:

• Purulent secretion reported as a symptom or found in the nasal cavity by the doctor
• Pain in the teeth
• Pain on bending forward (inconsistent findings between studies)
• Two phases in the illness history
• Elevated erythrocyte sedimentation rate or increased C-reactive protein
• Symptoms for at least 7 days

Lau and colleagues^5,10 reviewed 14 studies that compared various imaging studies with clinical evaluation or sinus puncture and aspiration with culture or both. A positive aspirate for bacterial pathogens was defined as the gold standard for diagnosis of sinusitis (Table).

X-ray vs sinus puncture. Depending on the criteria used to define a diagnosis of sinusitis on plain radiograph, estimates of sensitivity in these studies ranged from 0.41 to 0.90, and specificity estimates ranged from 0.61 to 0.85. Imaging studies that included “mucous membrane thickening” as a criterion for sinusitis were more sensitive but less specific than studies defining positive radiographs as “opacification of sinus.”

CT scan, MRI, ultrasound. While a CT scan is more sensitive than plain x-ray film,¹¹ and MRI is more sensitive than a CT scan,^12,13 the specificity of these studies is unclear. For example, in children and adults without symptoms of sinusitis, the prevalence of sinusitis signs on CT and MRI is 45% and 42%, respectively.^6,7,14 In light of such findings, these imaging methodologies are better reserved for patients in whom surgery is being contemplated, or for whom chronic sinusitis is a concern. In the 1980s and 1990s, ultrasound was studied enthusiastically. Variability in test performance is great.⁶ Since the cost of this procedure is similar to that of a sinus CT, ultrasound is not indicated in the diagnostic evaluation of the sinuses.

Though the sensitivity and specificity of a clinical evaluation possibly could be enhanced with the use of imaging studies, diagnostic accuracy of acute disease is not sufficiently improved to justify the cost or inconvenience of such interventions.

TABLE
Sensitivity and specificity of imaging modalities in sinusitis

Recommendations from others

In a guideline on appropriate antibiotic use in sinusitis,⁴ endorsed by the Centers for Disease Control and Prevention, American Academy of Family Physicians, the American College of Physicians–American Society of Internal Medicine, and the Infectious Diseases Society of America, radiography is not recommended for the diagnosis of acute sinusitis. The guideline recommends that clinicians rely on duration of illness (at least 7 days) and severity of symptoms to make an accurate diagnosis of sinusitis.

The American Academy of Allergy, Asthma and Immunology¹⁵ guideline makes the following recommendations regarding imaging:

• The use of imaging may be appropriate when there are vague symptoms, or poor response to initial management
• Standard radiographs are insensitive, but may be used for diagnosis of acute sinus disease
• CT is preferred for preoperative evaluation of the nose and paranasal sinuses
• MRI is very sensitive for diagnosis of soft tissue disease in the frontal, maxillary, and sphenoid sinuses
• Ultrasonography has limited utility but may be applicable in pregnant women and for determining the amount of retained secretions.

The Institute for Clinical Systems Improvement recommends that radiology be used only if initial treatment has failed, and notes that a primary goal of its guideline was to reduce the number of x-rays that physicians order for this diagnosis.¹⁶

The American College of Radiology’s criteria for sinusitis in the pediatric population ranked several radiographic studies based on their appropriateness for given clinical conditions. This review¹⁷ suggests that no imaging is appropriate if symptoms have persisted <10 days. For patients with symptoms lasting >10 days and with persistent fever, CT scan is recommended.

Evidence summary

Three recent evidence-based guidelines^3,4,5 suggest that children and adults with acute sinusitis may benefit from treatment with antibiotics more than those with rhinitis. Clinicians must develop a strategy for accurately diagnosing sinusitis to make sound treatment decisions. In the absence of a clear diagnosis of acute sinusitis, antibiotics are very unlikely to improve symptoms and are, therefore, not indicated.

Clinical evaluation. Berg¹ studied 150 patients with clinical diagnoses of sinusitis and found that 85% of them had positive sinus puncture. In a review of the 11 studies that met evidence-based inclusion criteria, Varonen⁶ concluded that clinical evaluation has a sensitivity of roughly 0.75, whereas radiographic methodologies have sensitivities >0.80. In a prospective trial and subsequent review of the literature, Lindbaek^7,8,9 suggests that several key clinical signs and symptoms can provide a level of sensitivity that approaches that of CT or magnetic resonance imaging (MRI), while enhancing specificity:

• Purulent secretion reported as a symptom or found in the nasal cavity by the doctor
• Pain in the teeth
• Pain on bending forward (inconsistent findings between studies)
• Two phases in the illness history
• Elevated erythrocyte sedimentation rate or increased C-reactive protein
• Symptoms for at least 7 days

Lau and colleagues^5,10 reviewed 14 studies that compared various imaging studies with clinical evaluation or sinus puncture and aspiration with culture or both. A positive aspirate for bacterial pathogens was defined as the gold standard for diagnosis of sinusitis (Table).

X-ray vs sinus puncture. Depending on the criteria used to define a diagnosis of sinusitis on plain radiograph, estimates of sensitivity in these studies ranged from 0.41 to 0.90, and specificity estimates ranged from 0.61 to 0.85. Imaging studies that included “mucous membrane thickening” as a criterion for sinusitis were more sensitive but less specific than studies defining positive radiographs as “opacification of sinus.”

CT scan, MRI, ultrasound. While a CT scan is more sensitive than plain x-ray film,¹¹ and MRI is more sensitive than a CT scan,^12,13 the specificity of these studies is unclear. For example, in children and adults without symptoms of sinusitis, the prevalence of sinusitis signs on CT and MRI is 45% and 42%, respectively.^6,7,14 In light of such findings, these imaging methodologies are better reserved for patients in whom surgery is being contemplated, or for whom chronic sinusitis is a concern. In the 1980s and 1990s, ultrasound was studied enthusiastically. Variability in test performance is great.⁶ Since the cost of this procedure is similar to that of a sinus CT, ultrasound is not indicated in the diagnostic evaluation of the sinuses.

Though the sensitivity and specificity of a clinical evaluation possibly could be enhanced with the use of imaging studies, diagnostic accuracy of acute disease is not sufficiently improved to justify the cost or inconvenience of such interventions.

TABLE
Sensitivity and specificity of imaging modalities in sinusitis

Recommendations from others

In a guideline on appropriate antibiotic use in sinusitis,⁴ endorsed by the Centers for Disease Control and Prevention, American Academy of Family Physicians, the American College of Physicians–American Society of Internal Medicine, and the Infectious Diseases Society of America, radiography is not recommended for the diagnosis of acute sinusitis. The guideline recommends that clinicians rely on duration of illness (at least 7 days) and severity of symptoms to make an accurate diagnosis of sinusitis.

The American Academy of Allergy, Asthma and Immunology¹⁵ guideline makes the following recommendations regarding imaging:

• The use of imaging may be appropriate when there are vague symptoms, or poor response to initial management
• Standard radiographs are insensitive, but may be used for diagnosis of acute sinus disease
• CT is preferred for preoperative evaluation of the nose and paranasal sinuses
• MRI is very sensitive for diagnosis of soft tissue disease in the frontal, maxillary, and sphenoid sinuses
• Ultrasonography has limited utility but may be applicable in pregnant women and for determining the amount of retained secretions.

The Institute for Clinical Systems Improvement recommends that radiology be used only if initial treatment has failed, and notes that a primary goal of its guideline was to reduce the number of x-rays that physicians order for this diagnosis.¹⁶

The American College of Radiology’s criteria for sinusitis in the pediatric population ranked several radiographic studies based on their appropriateness for given clinical conditions. This review¹⁷ suggests that no imaging is appropriate if symptoms have persisted <10 days. For patients with symptoms lasting >10 days and with persistent fever, CT scan is recommended.

Evidence summary

Three recent evidence-based guidelines^3,4,5 suggest that children and adults with acute sinusitis may benefit from treatment with antibiotics more than those with rhinitis. Clinicians must develop a strategy for accurately diagnosing sinusitis to make sound treatment decisions. In the absence of a clear diagnosis of acute sinusitis, antibiotics are very unlikely to improve symptoms and are, therefore, not indicated.

Clinical evaluation. Berg¹ studied 150 patients with clinical diagnoses of sinusitis and found that 85% of them had positive sinus puncture. In a review of the 11 studies that met evidence-based inclusion criteria, Varonen⁶ concluded that clinical evaluation has a sensitivity of roughly 0.75, whereas radiographic methodologies have sensitivities >0.80. In a prospective trial and subsequent review of the literature, Lindbaek^7,8,9 suggests that several key clinical signs and symptoms can provide a level of sensitivity that approaches that of CT or magnetic resonance imaging (MRI), while enhancing specificity:

• Purulent secretion reported as a symptom or found in the nasal cavity by the doctor
• Pain in the teeth
• Pain on bending forward (inconsistent findings between studies)
• Two phases in the illness history
• Elevated erythrocyte sedimentation rate or increased C-reactive protein
• Symptoms for at least 7 days

Lau and colleagues^5,10 reviewed 14 studies that compared various imaging studies with clinical evaluation or sinus puncture and aspiration with culture or both. A positive aspirate for bacterial pathogens was defined as the gold standard for diagnosis of sinusitis (Table).

X-ray vs sinus puncture. Depending on the criteria used to define a diagnosis of sinusitis on plain radiograph, estimates of sensitivity in these studies ranged from 0.41 to 0.90, and specificity estimates ranged from 0.61 to 0.85. Imaging studies that included “mucous membrane thickening” as a criterion for sinusitis were more sensitive but less specific than studies defining positive radiographs as “opacification of sinus.”

CT scan, MRI, ultrasound. While a CT scan is more sensitive than plain x-ray film,¹¹ and MRI is more sensitive than a CT scan,^12,13 the specificity of these studies is unclear. For example, in children and adults without symptoms of sinusitis, the prevalence of sinusitis signs on CT and MRI is 45% and 42%, respectively.^6,7,14 In light of such findings, these imaging methodologies are better reserved for patients in whom surgery is being contemplated, or for whom chronic sinusitis is a concern. In the 1980s and 1990s, ultrasound was studied enthusiastically. Variability in test performance is great.⁶ Since the cost of this procedure is similar to that of a sinus CT, ultrasound is not indicated in the diagnostic evaluation of the sinuses.

Though the sensitivity and specificity of a clinical evaluation possibly could be enhanced with the use of imaging studies, diagnostic accuracy of acute disease is not sufficiently improved to justify the cost or inconvenience of such interventions.

TABLE
Sensitivity and specificity of imaging modalities in sinusitis

Recommendations from others

In a guideline on appropriate antibiotic use in sinusitis,⁴ endorsed by the Centers for Disease Control and Prevention, American Academy of Family Physicians, the American College of Physicians–American Society of Internal Medicine, and the Infectious Diseases Society of America, radiography is not recommended for the diagnosis of acute sinusitis. The guideline recommends that clinicians rely on duration of illness (at least 7 days) and severity of symptoms to make an accurate diagnosis of sinusitis.

The American Academy of Allergy, Asthma and Immunology¹⁵ guideline makes the following recommendations regarding imaging:

• The use of imaging may be appropriate when there are vague symptoms, or poor response to initial management
• Standard radiographs are insensitive, but may be used for diagnosis of acute sinus disease
• CT is preferred for preoperative evaluation of the nose and paranasal sinuses
• MRI is very sensitive for diagnosis of soft tissue disease in the frontal, maxillary, and sphenoid sinuses
• Ultrasonography has limited utility but may be applicable in pregnant women and for determining the amount of retained secretions.

The Institute for Clinical Systems Improvement recommends that radiology be used only if initial treatment has failed, and notes that a primary goal of its guideline was to reduce the number of x-rays that physicians order for this diagnosis.¹⁶

The American College of Radiology’s criteria for sinusitis in the pediatric population ranked several radiographic studies based on their appropriateness for given clinical conditions. This review¹⁷ suggests that no imaging is appropriate if symptoms have persisted <10 days. For patients with symptoms lasting >10 days and with persistent fever, CT scan is recommended.

Evidence summary

In one series, 87% of patients with the common cold had an abnormal computed tomography (CT) scan of the sinuses 48 to 96 hours after onset. Abnormalities visible on the CT scan persisted in 20% of patients at 2 weeks, yet epidemiological studies have shown that acute bacterial rhinosinusitis develops in only 0.5% to 2% of upper respiratory infections in adults. In primary care, only half of patients with a clinical diagnosis of acute bacterial rhinosinusitis have it proven upon aspiration.⁵

Two studies compared clinical findings with sinus puncture, the reference standard for acute bacterial rhinosinusitis. Berg found 4 independent predictors of aspirate purulence in Swedish emergency room patients with “paranasal” symptoms lasting <3 months (Table).¹ Together, unilateral purulent nasal discharge and predominantly unilateral pain predicated purulence on aspiration (sensitivity 79%, specificity 83%, positive predictive value [PPV], 80%). Clinical exam by an otolaryngologist had a PPV of 72%.

While emergency and primary care patients may differ, this study’s rate of aspiration-proven sinusitis (43%) is closer to that seen in primary care (50%) than in referral practices (70%–80%). This study’s limitations included unclear referral criteria, overlapping clinical predictors, and lack of culture data.

In a study of general practice patients in the United Kingdom with clinically diagnosed acute maxillary sinusitis, no signs or symptoms were independently associated with their illness.⁶ The authors concluded that the clinical examination was more or less worthless. Only patients with positive findings on CT scan underwent aspiration in this study. Less differentiated, less severe symptoms and a less stringent definition of positive aspiration in this study may account for the different results. Additionally, one third of patients eligible for this study refused participation or withdrew prior to sinus puncture.⁶

Other primary care studies used less accurate reference tests such as CT² (sensitivity and specificity unknown),⁵ x-ray³ (sensitivity 41%–90%, specificity 61%–85%),⁵ and ultrasound⁴ (sensitivity 76%, specificity 76%).⁷

Williams found 5 independent predictors of x-ray findings consistent with sinusitis in 247 male veterans:

• maxillary toothache (LR+, 2.5)
• no improvement with decongestants (LR+, 2.1)
• purulent secretions on exam (LR+, 2.1)
• abnormal transillumination (LR+, 1.6)
• colored nasal discharge (LR+, 1.5).³

In at least 2 of these 4 studies, purulent secretions in the nasal cavity (LR+, 2.1–5.5),^2,3 maxillary tooth pain (LR+, 2.1–2.5)^3,4 and purulent rhinorrhea (LR+, 1.5–1.9)^2,3,4 increased the likelihood of acute bacterial rhinosinusitis.

Finding purulent secretions in the nasal cavity is highly specific for acute bacterial rhinosinusitis (specificity 79%–100%)^1,2,3 but is uncommon and difficult to assess, requiring the use of a nasal speculum and possibly topical decongestants. The primary care physician’s overall clinical impression was accurate in Williams’ study but not in others.^2,4,6 Illness starting as the common cold and pain on bending forward were not predictors of acute bacterial rhinosinusitis.^2,3,4 Headache, bilateral maxillary pain, frontal sinus pain, fever, sinus tenderness on exam, and purulent pharyngeal discharge have not been shown to be useful in acute bacterial rhinosinusitis diagnosis.⁷

TABLE
Clinical prediction rule for acute bacterial rhinosinusitis

Recommendations from others

A recommendation from the Agency for Health Care Policy and Research suggests using symptomatic treatment initially when the prevalence of acute bacterial rhinosinusitis in patients with upper respiratory infection is <25%, and using clinical criteria (see Table) for acute bacterial rhinosinusitis diagnosis when prevalence is higher.⁵

The Centers for Disease Control and Prevention recommends reserving the diagnosis of acute bacterial rhinosinusitis for patients with symptoms lasting ≥7 days with maxillary pain or tenderness in the face or teeth (especially unilateral) and purulent nasal secretions.⁸

An otolaryngology guideline recommends considering acute bacterial rhinosinusitis when viral upper respiratory infection persists beyond 10 days or worsens after 5 to 7 days with similar symptoms.⁹ The 7-to-10-day specification is based on the natural history of rhinovirus infections (SOR: C).

A Canadian Medical Association evidence-based review recommended a score based on Williams’ 5 independent predictor symptoms:

• fewer than 2 symptoms rule out acute bacterial rhinosinusitis (PPV, <40%)
• 4 or more symptoms rule in acute bacterial rhinosinusitis (PPV, 81%) (level of evidence [LOE]: 4)
• 2 or 3 symptoms (PPV, 40%–63%) may benefit from radiography (SOR: C).¹⁰

Evidence summary

In one series, 87% of patients with the common cold had an abnormal computed tomography (CT) scan of the sinuses 48 to 96 hours after onset. Abnormalities visible on the CT scan persisted in 20% of patients at 2 weeks, yet epidemiological studies have shown that acute bacterial rhinosinusitis develops in only 0.5% to 2% of upper respiratory infections in adults. In primary care, only half of patients with a clinical diagnosis of acute bacterial rhinosinusitis have it proven upon aspiration.⁵

Two studies compared clinical findings with sinus puncture, the reference standard for acute bacterial rhinosinusitis. Berg found 4 independent predictors of aspirate purulence in Swedish emergency room patients with “paranasal” symptoms lasting <3 months (Table).¹ Together, unilateral purulent nasal discharge and predominantly unilateral pain predicated purulence on aspiration (sensitivity 79%, specificity 83%, positive predictive value [PPV], 80%). Clinical exam by an otolaryngologist had a PPV of 72%.

While emergency and primary care patients may differ, this study’s rate of aspiration-proven sinusitis (43%) is closer to that seen in primary care (50%) than in referral practices (70%–80%). This study’s limitations included unclear referral criteria, overlapping clinical predictors, and lack of culture data.

In a study of general practice patients in the United Kingdom with clinically diagnosed acute maxillary sinusitis, no signs or symptoms were independently associated with their illness.⁶ The authors concluded that the clinical examination was more or less worthless. Only patients with positive findings on CT scan underwent aspiration in this study. Less differentiated, less severe symptoms and a less stringent definition of positive aspiration in this study may account for the different results. Additionally, one third of patients eligible for this study refused participation or withdrew prior to sinus puncture.⁶

Other primary care studies used less accurate reference tests such as CT² (sensitivity and specificity unknown),⁵ x-ray³ (sensitivity 41%–90%, specificity 61%–85%),⁵ and ultrasound⁴ (sensitivity 76%, specificity 76%).⁷

Williams found 5 independent predictors of x-ray findings consistent with sinusitis in 247 male veterans:

• maxillary toothache (LR+, 2.5)
• no improvement with decongestants (LR+, 2.1)
• purulent secretions on exam (LR+, 2.1)
• abnormal transillumination (LR+, 1.6)
• colored nasal discharge (LR+, 1.5).³

In at least 2 of these 4 studies, purulent secretions in the nasal cavity (LR+, 2.1–5.5),^2,3 maxillary tooth pain (LR+, 2.1–2.5)^3,4 and purulent rhinorrhea (LR+, 1.5–1.9)^2,3,4 increased the likelihood of acute bacterial rhinosinusitis.

Finding purulent secretions in the nasal cavity is highly specific for acute bacterial rhinosinusitis (specificity 79%–100%)^1,2,3 but is uncommon and difficult to assess, requiring the use of a nasal speculum and possibly topical decongestants. The primary care physician’s overall clinical impression was accurate in Williams’ study but not in others.^2,4,6 Illness starting as the common cold and pain on bending forward were not predictors of acute bacterial rhinosinusitis.^2,3,4 Headache, bilateral maxillary pain, frontal sinus pain, fever, sinus tenderness on exam, and purulent pharyngeal discharge have not been shown to be useful in acute bacterial rhinosinusitis diagnosis.⁷

TABLE
Clinical prediction rule for acute bacterial rhinosinusitis

Recommendations from others

A recommendation from the Agency for Health Care Policy and Research suggests using symptomatic treatment initially when the prevalence of acute bacterial rhinosinusitis in patients with upper respiratory infection is <25%, and using clinical criteria (see Table) for acute bacterial rhinosinusitis diagnosis when prevalence is higher.⁵

The Centers for Disease Control and Prevention recommends reserving the diagnosis of acute bacterial rhinosinusitis for patients with symptoms lasting ≥7 days with maxillary pain or tenderness in the face or teeth (especially unilateral) and purulent nasal secretions.⁸

An otolaryngology guideline recommends considering acute bacterial rhinosinusitis when viral upper respiratory infection persists beyond 10 days or worsens after 5 to 7 days with similar symptoms.⁹ The 7-to-10-day specification is based on the natural history of rhinovirus infections (SOR: C).

A Canadian Medical Association evidence-based review recommended a score based on Williams’ 5 independent predictor symptoms:

• fewer than 2 symptoms rule out acute bacterial rhinosinusitis (PPV, <40%)
• 4 or more symptoms rule in acute bacterial rhinosinusitis (PPV, 81%) (level of evidence [LOE]: 4)
• 2 or 3 symptoms (PPV, 40%–63%) may benefit from radiography (SOR: C).¹⁰

Evidence summary

In one series, 87% of patients with the common cold had an abnormal computed tomography (CT) scan of the sinuses 48 to 96 hours after onset. Abnormalities visible on the CT scan persisted in 20% of patients at 2 weeks, yet epidemiological studies have shown that acute bacterial rhinosinusitis develops in only 0.5% to 2% of upper respiratory infections in adults. In primary care, only half of patients with a clinical diagnosis of acute bacterial rhinosinusitis have it proven upon aspiration.⁵

Two studies compared clinical findings with sinus puncture, the reference standard for acute bacterial rhinosinusitis. Berg found 4 independent predictors of aspirate purulence in Swedish emergency room patients with “paranasal” symptoms lasting <3 months (Table).¹ Together, unilateral purulent nasal discharge and predominantly unilateral pain predicated purulence on aspiration (sensitivity 79%, specificity 83%, positive predictive value [PPV], 80%). Clinical exam by an otolaryngologist had a PPV of 72%.

While emergency and primary care patients may differ, this study’s rate of aspiration-proven sinusitis (43%) is closer to that seen in primary care (50%) than in referral practices (70%–80%). This study’s limitations included unclear referral criteria, overlapping clinical predictors, and lack of culture data.

In a study of general practice patients in the United Kingdom with clinically diagnosed acute maxillary sinusitis, no signs or symptoms were independently associated with their illness.⁶ The authors concluded that the clinical examination was more or less worthless. Only patients with positive findings on CT scan underwent aspiration in this study. Less differentiated, less severe symptoms and a less stringent definition of positive aspiration in this study may account for the different results. Additionally, one third of patients eligible for this study refused participation or withdrew prior to sinus puncture.⁶

Other primary care studies used less accurate reference tests such as CT² (sensitivity and specificity unknown),⁵ x-ray³ (sensitivity 41%–90%, specificity 61%–85%),⁵ and ultrasound⁴ (sensitivity 76%, specificity 76%).⁷

Williams found 5 independent predictors of x-ray findings consistent with sinusitis in 247 male veterans:

• maxillary toothache (LR+, 2.5)
• no improvement with decongestants (LR+, 2.1)
• purulent secretions on exam (LR+, 2.1)
• abnormal transillumination (LR+, 1.6)
• colored nasal discharge (LR+, 1.5).³

In at least 2 of these 4 studies, purulent secretions in the nasal cavity (LR+, 2.1–5.5),^2,3 maxillary tooth pain (LR+, 2.1–2.5)^3,4 and purulent rhinorrhea (LR+, 1.5–1.9)^2,3,4 increased the likelihood of acute bacterial rhinosinusitis.

Finding purulent secretions in the nasal cavity is highly specific for acute bacterial rhinosinusitis (specificity 79%–100%)^1,2,3 but is uncommon and difficult to assess, requiring the use of a nasal speculum and possibly topical decongestants. The primary care physician’s overall clinical impression was accurate in Williams’ study but not in others.^2,4,6 Illness starting as the common cold and pain on bending forward were not predictors of acute bacterial rhinosinusitis.^2,3,4 Headache, bilateral maxillary pain, frontal sinus pain, fever, sinus tenderness on exam, and purulent pharyngeal discharge have not been shown to be useful in acute bacterial rhinosinusitis diagnosis.⁷

TABLE
Clinical prediction rule for acute bacterial rhinosinusitis

Recommendations from others

A recommendation from the Agency for Health Care Policy and Research suggests using symptomatic treatment initially when the prevalence of acute bacterial rhinosinusitis in patients with upper respiratory infection is <25%, and using clinical criteria (see Table) for acute bacterial rhinosinusitis diagnosis when prevalence is higher.⁵

The Centers for Disease Control and Prevention recommends reserving the diagnosis of acute bacterial rhinosinusitis for patients with symptoms lasting ≥7 days with maxillary pain or tenderness in the face or teeth (especially unilateral) and purulent nasal secretions.⁸

An otolaryngology guideline recommends considering acute bacterial rhinosinusitis when viral upper respiratory infection persists beyond 10 days or worsens after 5 to 7 days with similar symptoms.⁹ The 7-to-10-day specification is based on the natural history of rhinovirus infections (SOR: C).

A Canadian Medical Association evidence-based review recommended a score based on Williams’ 5 independent predictor symptoms:

• fewer than 2 symptoms rule out acute bacterial rhinosinusitis (PPV, <40%)
• 4 or more symptoms rule in acute bacterial rhinosinusitis (PPV, 81%) (level of evidence [LOE]: 4)
• 2 or 3 symptoms (PPV, 40%–63%) may benefit from radiography (SOR: C).¹⁰

Evidence summary

Intracranial aneurysms are not rare. Based on autopsy data, prevalence has been estimated to be 0.2% to 9.9% of the population.¹ Ten to 15 million Americans may have unruptured intracranial aneurysms, most of which remain undiagnosed.²

Conditions leading to the diagnosis of unruptured intracranial aneurysms include:

• headache (in 36% of patients)
• ischemic cerebrovascular disease (17.6%)
• cranial nerve deficits (15.4 %)
• aneurysmal mass effect (5.7%)
• ill-defined “spells” (4.8%)
• convulsive disorder (4.2%)
• subdural or intracerebral hemorrhage (2.7%)
• brain tumor (1.7%)
• nervous system degenerative disease (0.5%).²

No randomized controlled trials have examined whether unruptured intracranial aneurysms should be treated surgically. In the absence of a clinical trial, the evidence to answer this question is based on observational, cohort, and case-control studies, where the risks of the natural history of the condition are weighed against the risks of surgical intervention.³

One study of the natural history of unruptured cerebral aneurysm included 130 patients with 161 unruptured intracranial aneurysms who were followed for a mean of 8.3 years.^4,5 This prospective investigation found that 15 patients suffered an intracranial hemorrhage. There were no ruptures of the 102 aneurysms that were ≤10 mm in diameter at the time of discovery.^4,5

In the largest cohort study to date, patients without a history of subarachnoid hemorrhage had an overall risk of rupture of 0.05% per year over 7.5 years. This study also found that surgery-related morbidity and mortality at 1 year among patients aged <45 years was 6.5%, compared with 14.4% for those aged 45 to 64 years, and 32% for those aged >64 years.²

Recommendations from others

The Stroke Council of the American Heart Association recommends that observation is generally appropriate for incidental, small (<10-mm) aneurysms in patients without previous subarachnoid hemorrhage. However, special consideration for treatment should be given to young patients in this group, small aneurysms approaching the 10-mm size, and aneurysms with daughter sac formation ( Figure). In addition, patients with a family history of aneurysm or aneurysmal subarachnoid hemorrhage deserve special consideration for treatment.

For patients managed conservatively, periodic follow-up imaging should be considered; imaging is necessary if a specific symptom should arise. If changes in aneurysmal size or configuration are observed, special consideration for treatment should be made.⁶

Aneurysm with daughter sac

Evidence summary

Intracranial aneurysms are not rare. Based on autopsy data, prevalence has been estimated to be 0.2% to 9.9% of the population.¹ Ten to 15 million Americans may have unruptured intracranial aneurysms, most of which remain undiagnosed.²

Conditions leading to the diagnosis of unruptured intracranial aneurysms include:

• headache (in 36% of patients)
• ischemic cerebrovascular disease (17.6%)
• cranial nerve deficits (15.4 %)
• aneurysmal mass effect (5.7%)
• ill-defined “spells” (4.8%)
• convulsive disorder (4.2%)
• subdural or intracerebral hemorrhage (2.7%)
• brain tumor (1.7%)
• nervous system degenerative disease (0.5%).²

No randomized controlled trials have examined whether unruptured intracranial aneurysms should be treated surgically. In the absence of a clinical trial, the evidence to answer this question is based on observational, cohort, and case-control studies, where the risks of the natural history of the condition are weighed against the risks of surgical intervention.³

One study of the natural history of unruptured cerebral aneurysm included 130 patients with 161 unruptured intracranial aneurysms who were followed for a mean of 8.3 years.^4,5 This prospective investigation found that 15 patients suffered an intracranial hemorrhage. There were no ruptures of the 102 aneurysms that were ≤10 mm in diameter at the time of discovery.^4,5

In the largest cohort study to date, patients without a history of subarachnoid hemorrhage had an overall risk of rupture of 0.05% per year over 7.5 years. This study also found that surgery-related morbidity and mortality at 1 year among patients aged <45 years was 6.5%, compared with 14.4% for those aged 45 to 64 years, and 32% for those aged >64 years.²

Recommendations from others

The Stroke Council of the American Heart Association recommends that observation is generally appropriate for incidental, small (<10-mm) aneurysms in patients without previous subarachnoid hemorrhage. However, special consideration for treatment should be given to young patients in this group, small aneurysms approaching the 10-mm size, and aneurysms with daughter sac formation ( Figure). In addition, patients with a family history of aneurysm or aneurysmal subarachnoid hemorrhage deserve special consideration for treatment.

For patients managed conservatively, periodic follow-up imaging should be considered; imaging is necessary if a specific symptom should arise. If changes in aneurysmal size or configuration are observed, special consideration for treatment should be made.⁶

Aneurysm with daughter sac

Evidence summary

Intracranial aneurysms are not rare. Based on autopsy data, prevalence has been estimated to be 0.2% to 9.9% of the population.¹ Ten to 15 million Americans may have unruptured intracranial aneurysms, most of which remain undiagnosed.²

Conditions leading to the diagnosis of unruptured intracranial aneurysms include:

• headache (in 36% of patients)
• ischemic cerebrovascular disease (17.6%)
• cranial nerve deficits (15.4 %)
• aneurysmal mass effect (5.7%)
• ill-defined “spells” (4.8%)
• convulsive disorder (4.2%)
• subdural or intracerebral hemorrhage (2.7%)
• brain tumor (1.7%)
• nervous system degenerative disease (0.5%).²

No randomized controlled trials have examined whether unruptured intracranial aneurysms should be treated surgically. In the absence of a clinical trial, the evidence to answer this question is based on observational, cohort, and case-control studies, where the risks of the natural history of the condition are weighed against the risks of surgical intervention.³

One study of the natural history of unruptured cerebral aneurysm included 130 patients with 161 unruptured intracranial aneurysms who were followed for a mean of 8.3 years.^4,5 This prospective investigation found that 15 patients suffered an intracranial hemorrhage. There were no ruptures of the 102 aneurysms that were ≤10 mm in diameter at the time of discovery.^4,5

In the largest cohort study to date, patients without a history of subarachnoid hemorrhage had an overall risk of rupture of 0.05% per year over 7.5 years. This study also found that surgery-related morbidity and mortality at 1 year among patients aged <45 years was 6.5%, compared with 14.4% for those aged 45 to 64 years, and 32% for those aged >64 years.²

Recommendations from others

The Stroke Council of the American Heart Association recommends that observation is generally appropriate for incidental, small (<10-mm) aneurysms in patients without previous subarachnoid hemorrhage. However, special consideration for treatment should be given to young patients in this group, small aneurysms approaching the 10-mm size, and aneurysms with daughter sac formation ( Figure). In addition, patients with a family history of aneurysm or aneurysmal subarachnoid hemorrhage deserve special consideration for treatment.

For patients managed conservatively, periodic follow-up imaging should be considered; imaging is necessary if a specific symptom should arise. If changes in aneurysmal size or configuration are observed, special consideration for treatment should be made.⁶

Aneurysm with daughter sac

Evidence summary

Postherpetic neuralgia is defined as pain that persists more than 1 month following onset of herpes zoster. The annual incidence of herpes zoster in population-based studies ranges from 1/1000 to 2/1000.^1,3 Among adults aged >60 years, the annual incidence increases to 3.6/1000 for men and 5.6/1000 for women.¹

In a prospective study performed in a primary care setting in Iceland, all cases of herpes zoster and postherpetic neuralgia occurring over 4.5 years in a population of 100,000 were identified, and all cases of postherpetic neuralgia were followed for up to 7.6 years. Few patients (4%) received antiviral medication.

In this study, postherpetic neuralgia followed herpes zoster in 2% of patients under age 40, 21% between the ages of 40 and 60, and in 40% of those over age 60.^1,2 Subjects self-described pain as none, mild, moderate, or severe. Patients aged >60 years had the worst prognosis: 18% still had mild pain at 3 months and 6% had moderate or severe pain. At 1 year, 8% had mild pain and 2% had moderate pain. No patients had severe pain after 12 months.^1,2

Among the 14 patients with pain persisting >12 months, 7 had complete resolution of pain, 5 had persisting pain that either improved or remained mild, 1 had ongoing moderate pain at 7 years, and 1 was lost to follow-up.² (See Table.) Although postherpetic neuralgia can recur after resolution,⁴ no recurrence of pain was found among 183 randomly selected patients who had had resolution by 1 year.²

These results are similar to those found in an analysis of a retrospective cohort drawn from a large general practice network database,⁵ as well as other population-based studies.^6,7 The prognosis is better than that reported in the placebo arms of trials of acute herpes zoster treatment.⁴ Patients in such trials are more likely to have severe disease than those seen in primary care settings.

TABLE
Risk of postherpetic neuralgia by age

Recommendations from others

A British guideline states that 5% of herpes zoster patients have postherpetic neuralgia 1 year after shingles.⁸ A review in the New England Journal of Medicine states that 48% of herpes zoster patients aged >70 years have postherpetic neuralgia at 1 year.⁹ This prevalence comes from a retrospective cohort study that combined patients presenting to a referral center with herpes zoster or postherpetic neuralgia into a single cohort, thus overestimating the prevalence of postherpetic neuralgia and providing a less reliable prognosis.¹⁰

Evidence summary

Postherpetic neuralgia is defined as pain that persists more than 1 month following onset of herpes zoster. The annual incidence of herpes zoster in population-based studies ranges from 1/1000 to 2/1000.^1,3 Among adults aged >60 years, the annual incidence increases to 3.6/1000 for men and 5.6/1000 for women.¹

In a prospective study performed in a primary care setting in Iceland, all cases of herpes zoster and postherpetic neuralgia occurring over 4.5 years in a population of 100,000 were identified, and all cases of postherpetic neuralgia were followed for up to 7.6 years. Few patients (4%) received antiviral medication.

In this study, postherpetic neuralgia followed herpes zoster in 2% of patients under age 40, 21% between the ages of 40 and 60, and in 40% of those over age 60.^1,2 Subjects self-described pain as none, mild, moderate, or severe. Patients aged >60 years had the worst prognosis: 18% still had mild pain at 3 months and 6% had moderate or severe pain. At 1 year, 8% had mild pain and 2% had moderate pain. No patients had severe pain after 12 months.^1,2

Among the 14 patients with pain persisting >12 months, 7 had complete resolution of pain, 5 had persisting pain that either improved or remained mild, 1 had ongoing moderate pain at 7 years, and 1 was lost to follow-up.² (See Table.) Although postherpetic neuralgia can recur after resolution,⁴ no recurrence of pain was found among 183 randomly selected patients who had had resolution by 1 year.²

These results are similar to those found in an analysis of a retrospective cohort drawn from a large general practice network database,⁵ as well as other population-based studies.^6,7 The prognosis is better than that reported in the placebo arms of trials of acute herpes zoster treatment.⁴ Patients in such trials are more likely to have severe disease than those seen in primary care settings.

TABLE
Risk of postherpetic neuralgia by age

Recommendations from others

A British guideline states that 5% of herpes zoster patients have postherpetic neuralgia 1 year after shingles.⁸ A review in the New England Journal of Medicine states that 48% of herpes zoster patients aged >70 years have postherpetic neuralgia at 1 year.⁹ This prevalence comes from a retrospective cohort study that combined patients presenting to a referral center with herpes zoster or postherpetic neuralgia into a single cohort, thus overestimating the prevalence of postherpetic neuralgia and providing a less reliable prognosis.¹⁰

Evidence summary

Postherpetic neuralgia is defined as pain that persists more than 1 month following onset of herpes zoster. The annual incidence of herpes zoster in population-based studies ranges from 1/1000 to 2/1000.^1,3 Among adults aged >60 years, the annual incidence increases to 3.6/1000 for men and 5.6/1000 for women.¹

In a prospective study performed in a primary care setting in Iceland, all cases of herpes zoster and postherpetic neuralgia occurring over 4.5 years in a population of 100,000 were identified, and all cases of postherpetic neuralgia were followed for up to 7.6 years. Few patients (4%) received antiviral medication.

In this study, postherpetic neuralgia followed herpes zoster in 2% of patients under age 40, 21% between the ages of 40 and 60, and in 40% of those over age 60.^1,2 Subjects self-described pain as none, mild, moderate, or severe. Patients aged >60 years had the worst prognosis: 18% still had mild pain at 3 months and 6% had moderate or severe pain. At 1 year, 8% had mild pain and 2% had moderate pain. No patients had severe pain after 12 months.^1,2

Among the 14 patients with pain persisting >12 months, 7 had complete resolution of pain, 5 had persisting pain that either improved or remained mild, 1 had ongoing moderate pain at 7 years, and 1 was lost to follow-up.² (See Table.) Although postherpetic neuralgia can recur after resolution,⁴ no recurrence of pain was found among 183 randomly selected patients who had had resolution by 1 year.²

These results are similar to those found in an analysis of a retrospective cohort drawn from a large general practice network database,⁵ as well as other population-based studies.^6,7 The prognosis is better than that reported in the placebo arms of trials of acute herpes zoster treatment.⁴ Patients in such trials are more likely to have severe disease than those seen in primary care settings.

TABLE
Risk of postherpetic neuralgia by age

Recommendations from others

A British guideline states that 5% of herpes zoster patients have postherpetic neuralgia 1 year after shingles.⁸ A review in the New England Journal of Medicine states that 48% of herpes zoster patients aged >70 years have postherpetic neuralgia at 1 year.⁹ This prevalence comes from a retrospective cohort study that combined patients presenting to a referral center with herpes zoster or postherpetic neuralgia into a single cohort, thus overestimating the prevalence of postherpetic neuralgia and providing a less reliable prognosis.¹⁰

Evidence summary

A Cochrane Review of 110 trials evaluating the efficacy of nicotine replacement therapy in 35,600 smokers found higher quit rates among heavy smokers using 4-mg compared with 2-mg nicotine gum (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.69–4.22).¹ However, patients often chew too few pieces of nicotine gum daily, resulting in underdosing.³ Smokers should use the gum on a fixed schedule (at least 1 piece every 1 to 2 hours).³

The Cochrane Review finds borderline evidence of a small benefit in abstinence rates (OR, 1.21; 95% CI, 1.03–1.42) with higher-dose nicotine patches (>21 mg/24 hr or 15 mg/16 hr) for heavy or relapsed smokers.¹ Combining methods that maintain constant drug levels (transdermal patch) with those having more rapid effects (gum, spray, inhaler, lozenge) is more effective than monotherapy (OR, 1.9; 95% CI, 1.3–2.6).³ Reserve combination therapy for smokers who relapse following monotherapy.

Regarding concerns about weight gain, all nicotine replacement therapies delay but do not prevent weight gain. There is a dose-response relationship between nicotine gum and weight gain: smokers who use more gum gain less weight.³ Although abstinence rates are comparable across the 5 available forms of nicotine replacement, smokers unwilling to give up oral and behavioral rituals of smoking may perceive the inhaler as being more helpful (Table 1).⁴

Decisions about the best form of therapy can be based on patient preference, on degree of nicotine dependence (a Fagerström Test of Nicotine Dependence Scale score ≥5 [Table 2], or habitually smoking the first cigarette within 30 minutes of awakening),⁵ or nicotine replacement therapy history, which includes number and outcome of previous quit attempts, specific method used, duration, side effects, and proper usage.

Recommendations from others

The Cochrane Review states: “All of the commercially available forms of nicotine replacement therapy are effective as part of a strategy to promote smoking cessation. They increase quit rates approximately 1.5 to 2 fold regardless of setting. Use of nicotine replacement therapy should be preferentially directed to smokers who are motivated to quit, and have high levels of nicotine dependency. Choice of which form to use should reflect patient needs, tolerability and cost considerations. Patches are likely to be easier to use than gum or nasal spray in primary care settings.”¹

The US Department of Health and Human Services Clinical Practice Guideline states: “All patients attempting to quit should be encouraged to use effective pharmacotherapies for smoking cessation except in the presence of special circumstances.”³ Heavy smokers should use 4-mg nicotine gum. Combining the nicotine patch with a self-administered form of nicotine replacement therapy (gum or nicotine nasal spray) is more efficacious than a single form of therapy. Patients should be encouraged to use combined treatments if unable to quit using a single form of first-line pharmacotherapy.³

TABLE 1
Nicotine replacement therapy selection guide

TABLE 2
Fagerström test for level of nicotine dependence (abridged)

Evidence summary

A Cochrane Review of 110 trials evaluating the efficacy of nicotine replacement therapy in 35,600 smokers found higher quit rates among heavy smokers using 4-mg compared with 2-mg nicotine gum (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.69–4.22).¹ However, patients often chew too few pieces of nicotine gum daily, resulting in underdosing.³ Smokers should use the gum on a fixed schedule (at least 1 piece every 1 to 2 hours).³

The Cochrane Review finds borderline evidence of a small benefit in abstinence rates (OR, 1.21; 95% CI, 1.03–1.42) with higher-dose nicotine patches (>21 mg/24 hr or 15 mg/16 hr) for heavy or relapsed smokers.¹ Combining methods that maintain constant drug levels (transdermal patch) with those having more rapid effects (gum, spray, inhaler, lozenge) is more effective than monotherapy (OR, 1.9; 95% CI, 1.3–2.6).³ Reserve combination therapy for smokers who relapse following monotherapy.

Regarding concerns about weight gain, all nicotine replacement therapies delay but do not prevent weight gain. There is a dose-response relationship between nicotine gum and weight gain: smokers who use more gum gain less weight.³ Although abstinence rates are comparable across the 5 available forms of nicotine replacement, smokers unwilling to give up oral and behavioral rituals of smoking may perceive the inhaler as being more helpful (Table 1).⁴

Decisions about the best form of therapy can be based on patient preference, on degree of nicotine dependence (a Fagerström Test of Nicotine Dependence Scale score ≥5 [Table 2], or habitually smoking the first cigarette within 30 minutes of awakening),⁵ or nicotine replacement therapy history, which includes number and outcome of previous quit attempts, specific method used, duration, side effects, and proper usage.

Recommendations from others

The Cochrane Review states: “All of the commercially available forms of nicotine replacement therapy are effective as part of a strategy to promote smoking cessation. They increase quit rates approximately 1.5 to 2 fold regardless of setting. Use of nicotine replacement therapy should be preferentially directed to smokers who are motivated to quit, and have high levels of nicotine dependency. Choice of which form to use should reflect patient needs, tolerability and cost considerations. Patches are likely to be easier to use than gum or nasal spray in primary care settings.”¹

The US Department of Health and Human Services Clinical Practice Guideline states: “All patients attempting to quit should be encouraged to use effective pharmacotherapies for smoking cessation except in the presence of special circumstances.”³ Heavy smokers should use 4-mg nicotine gum. Combining the nicotine patch with a self-administered form of nicotine replacement therapy (gum or nicotine nasal spray) is more efficacious than a single form of therapy. Patients should be encouraged to use combined treatments if unable to quit using a single form of first-line pharmacotherapy.³

TABLE 1
Nicotine replacement therapy selection guide

TABLE 2
Fagerström test for level of nicotine dependence (abridged)

Evidence summary

A Cochrane Review of 110 trials evaluating the efficacy of nicotine replacement therapy in 35,600 smokers found higher quit rates among heavy smokers using 4-mg compared with 2-mg nicotine gum (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.69–4.22).¹ However, patients often chew too few pieces of nicotine gum daily, resulting in underdosing.³ Smokers should use the gum on a fixed schedule (at least 1 piece every 1 to 2 hours).³

The Cochrane Review finds borderline evidence of a small benefit in abstinence rates (OR, 1.21; 95% CI, 1.03–1.42) with higher-dose nicotine patches (>21 mg/24 hr or 15 mg/16 hr) for heavy or relapsed smokers.¹ Combining methods that maintain constant drug levels (transdermal patch) with those having more rapid effects (gum, spray, inhaler, lozenge) is more effective than monotherapy (OR, 1.9; 95% CI, 1.3–2.6).³ Reserve combination therapy for smokers who relapse following monotherapy.

Regarding concerns about weight gain, all nicotine replacement therapies delay but do not prevent weight gain. There is a dose-response relationship between nicotine gum and weight gain: smokers who use more gum gain less weight.³ Although abstinence rates are comparable across the 5 available forms of nicotine replacement, smokers unwilling to give up oral and behavioral rituals of smoking may perceive the inhaler as being more helpful (Table 1).⁴

Decisions about the best form of therapy can be based on patient preference, on degree of nicotine dependence (a Fagerström Test of Nicotine Dependence Scale score ≥5 [Table 2], or habitually smoking the first cigarette within 30 minutes of awakening),⁵ or nicotine replacement therapy history, which includes number and outcome of previous quit attempts, specific method used, duration, side effects, and proper usage.

Recommendations from others

The Cochrane Review states: “All of the commercially available forms of nicotine replacement therapy are effective as part of a strategy to promote smoking cessation. They increase quit rates approximately 1.5 to 2 fold regardless of setting. Use of nicotine replacement therapy should be preferentially directed to smokers who are motivated to quit, and have high levels of nicotine dependency. Choice of which form to use should reflect patient needs, tolerability and cost considerations. Patches are likely to be easier to use than gum or nasal spray in primary care settings.”¹

The US Department of Health and Human Services Clinical Practice Guideline states: “All patients attempting to quit should be encouraged to use effective pharmacotherapies for smoking cessation except in the presence of special circumstances.”³ Heavy smokers should use 4-mg nicotine gum. Combining the nicotine patch with a self-administered form of nicotine replacement therapy (gum or nicotine nasal spray) is more efficacious than a single form of therapy. Patients should be encouraged to use combined treatments if unable to quit using a single form of first-line pharmacotherapy.³

TABLE 1
Nicotine replacement therapy selection guide

TABLE 2
Fagerström test for level of nicotine dependence (abridged)

Evidence summary

Nearly all trials comparing placebo with antibiotics for maxillary sinusitis are confounded by the difficulty in identifying true bacterial disease. The gold standard, sinus aspiration, offers the best diagnostic accuracy. CT scanning and plain radiography lack sufficient diagnostic accuracy to be useful alone, though CT scans offer better sensitivity.

One systematic review, limited to randomized controlled trials that required either radiographic or aspiration evidence of sinusitis, found penicillin superior to placebo,⁴ but all patients recovered in a few weeks regardless of treatment. Given that radiographs have poor diagnostic accuracy⁵ and that sinus aspiration is impractical in outpatient practice, such efficacy studies are less meaningful than effectiveness studies that use clinical criteria for study entry and outcome measurement.

No accurate clinical diagnostic criteria have been established. In ear, nose, and throat practices where bacterial sinusitis prevalence is high, clinical criteria identify only 70%–80% of cases compared with the sinus aspiration.⁶ In general practice, where the pretest probability of bacterial disease is far lower, clinical criteria are even less reliable,¹ which confounds the interpretation of most clinical trials.

Accordingly, some placebo-controlled, primary-care–based clinical trials have shown symptomatic benefit of antibiotics for maxillary sinusitis^7,8,9 while others have shown no benefit whatsoever.^10,11,12 In those trials that demonstrated a significant difference, antibiotics were always more likely than placebo to cause side effects, and no control group fared worse than its matched antibiotic group by the end of a follow-up period of at least 25 days.

It is likely that antibiotics would be more useful if the subgroup of patients with bacterial disease could be accurately identified in outpatient practice. For the present, given that no such reliable criteria exist, that withholding antibiotics in these patients appears to be safe, and that antibiotic overuse has clear harm to individuals and society, sinusitis symptoms should be treated without antibiotics until the clinical course strongly suggests nonviral illness.

Recommendations from others

An evidence report from the Agency for Health Care Policy and Research recommends “initial symptomatic treatment or the use of clinical criteria to guide treatment.”¹ The American Academy of Family Physicians “recognizes inappropriate use of antibiotics as a risk to both personal and public health and encourages only the appropriate use of these medications,”¹³ but has not published sinusitis guidelines. The Centers for Disease Control and most authorities suggest that bacterial disease can be inferred in those with signs or symptoms that suggest bacterial rather than viral illness (eg, overall duration of symptoms, so-called “double-sickening,” unilateral symptoms) and justify use of antibiotics in these patients.

Evidence summary

Nearly all trials comparing placebo with antibiotics for maxillary sinusitis are confounded by the difficulty in identifying true bacterial disease. The gold standard, sinus aspiration, offers the best diagnostic accuracy. CT scanning and plain radiography lack sufficient diagnostic accuracy to be useful alone, though CT scans offer better sensitivity.

One systematic review, limited to randomized controlled trials that required either radiographic or aspiration evidence of sinusitis, found penicillin superior to placebo,⁴ but all patients recovered in a few weeks regardless of treatment. Given that radiographs have poor diagnostic accuracy⁵ and that sinus aspiration is impractical in outpatient practice, such efficacy studies are less meaningful than effectiveness studies that use clinical criteria for study entry and outcome measurement.

No accurate clinical diagnostic criteria have been established. In ear, nose, and throat practices where bacterial sinusitis prevalence is high, clinical criteria identify only 70%–80% of cases compared with the sinus aspiration.⁶ In general practice, where the pretest probability of bacterial disease is far lower, clinical criteria are even less reliable,¹ which confounds the interpretation of most clinical trials.

Accordingly, some placebo-controlled, primary-care–based clinical trials have shown symptomatic benefit of antibiotics for maxillary sinusitis^7,8,9 while others have shown no benefit whatsoever.^10,11,12 In those trials that demonstrated a significant difference, antibiotics were always more likely than placebo to cause side effects, and no control group fared worse than its matched antibiotic group by the end of a follow-up period of at least 25 days.

It is likely that antibiotics would be more useful if the subgroup of patients with bacterial disease could be accurately identified in outpatient practice. For the present, given that no such reliable criteria exist, that withholding antibiotics in these patients appears to be safe, and that antibiotic overuse has clear harm to individuals and society, sinusitis symptoms should be treated without antibiotics until the clinical course strongly suggests nonviral illness.

Recommendations from others

An evidence report from the Agency for Health Care Policy and Research recommends “initial symptomatic treatment or the use of clinical criteria to guide treatment.”¹ The American Academy of Family Physicians “recognizes inappropriate use of antibiotics as a risk to both personal and public health and encourages only the appropriate use of these medications,”¹³ but has not published sinusitis guidelines. The Centers for Disease Control and most authorities suggest that bacterial disease can be inferred in those with signs or symptoms that suggest bacterial rather than viral illness (eg, overall duration of symptoms, so-called “double-sickening,” unilateral symptoms) and justify use of antibiotics in these patients.

Evidence summary

Nearly all trials comparing placebo with antibiotics for maxillary sinusitis are confounded by the difficulty in identifying true bacterial disease. The gold standard, sinus aspiration, offers the best diagnostic accuracy. CT scanning and plain radiography lack sufficient diagnostic accuracy to be useful alone, though CT scans offer better sensitivity.

One systematic review, limited to randomized controlled trials that required either radiographic or aspiration evidence of sinusitis, found penicillin superior to placebo,⁴ but all patients recovered in a few weeks regardless of treatment. Given that radiographs have poor diagnostic accuracy⁵ and that sinus aspiration is impractical in outpatient practice, such efficacy studies are less meaningful than effectiveness studies that use clinical criteria for study entry and outcome measurement.

No accurate clinical diagnostic criteria have been established. In ear, nose, and throat practices where bacterial sinusitis prevalence is high, clinical criteria identify only 70%–80% of cases compared with the sinus aspiration.⁶ In general practice, where the pretest probability of bacterial disease is far lower, clinical criteria are even less reliable,¹ which confounds the interpretation of most clinical trials.

Accordingly, some placebo-controlled, primary-care–based clinical trials have shown symptomatic benefit of antibiotics for maxillary sinusitis^7,8,9 while others have shown no benefit whatsoever.^10,11,12 In those trials that demonstrated a significant difference, antibiotics were always more likely than placebo to cause side effects, and no control group fared worse than its matched antibiotic group by the end of a follow-up period of at least 25 days.

It is likely that antibiotics would be more useful if the subgroup of patients with bacterial disease could be accurately identified in outpatient practice. For the present, given that no such reliable criteria exist, that withholding antibiotics in these patients appears to be safe, and that antibiotic overuse has clear harm to individuals and society, sinusitis symptoms should be treated without antibiotics until the clinical course strongly suggests nonviral illness.

Recommendations from others

An evidence report from the Agency for Health Care Policy and Research recommends “initial symptomatic treatment or the use of clinical criteria to guide treatment.”¹ The American Academy of Family Physicians “recognizes inappropriate use of antibiotics as a risk to both personal and public health and encourages only the appropriate use of these medications,”¹³ but has not published sinusitis guidelines. The Centers for Disease Control and most authorities suggest that bacterial disease can be inferred in those with signs or symptoms that suggest bacterial rather than viral illness (eg, overall duration of symptoms, so-called “double-sickening,” unilateral symptoms) and justify use of antibiotics in these patients.

Evidence summary

Four cohort studies of patients with diabetes have compared overall mean blood glucose levels with HbA1c levels.^1-4 All but one⁴ were limited to patients with type 1 diabetes. Study periods ranged from 1 to 6 months, and frequency of blood glucose measurement ranged from 2 to 4 times per day.

Correlation coefficients between mean blood glucose levels and HbA1c levels ranged from 0.71 to 0.86, implying that 50% to 74% of the variance in HbA1c is explained by the mean blood glucose (in each study, correlation was significant [P<.02]).

We found 5 studies comparing blood glucose measurements at specific times of day with HbA1c levels see (Table). Data from 3 studies comparing blood glucose values after lunchtime with those earlier in the day suggest that the lunchtime levels are more closely associated with HbA1c levels.^5,7,9 No consistent difference was shown between preprandial and postprandial blood glucose levels in their strength of association with HbA1c levels. In 1 of these studies, a blood glucose level of 150 mg/dL 2 hours after lunch predicted a HbA1c of 7% with 85% sensitivity and 85% specificity.⁷ One study provided only limited information on blood glucose–HbA1c correlations in relation to mealtimes but did report that the times of day at which the 2 were best correlated were in the periods from midnight to 5:00 AM and between noon and 3:00 PM.⁹ One study compared patients with type 1 and type 2 diabetes and found a higher correlation between blood glucose and HbA1c levels in the latter.⁶

The relationship between HbA1c and blood glucose levels is such that blood glucose levels from the preceding 30 days determine about 50% of the total HbA1c.¹⁰ This relationship may be altered by uremia, intake of vitamins C or E, and conditions that affect erythrocyte turnover.¹¹

It remains unclear whether management strategies that focus on minimizing HbA1c levels are optimal for prevention of diabetic complications.

Although HbA1c levels correlate with the risk of some complications, aspects of glycemia not reflected in the HbA1c level, such as the heights of glycemic “excursions” from the mean, may independently affect the risk of complications of diabetes.¹² If so, quantitative analysis of day-to-day blood glucose levels might yield a better estimation of the risk of diabetic complications than HbA1c levels.

TABLE
Correlation coefficients between blood glucose levels and hemoglobin A1c levels

Recommendations from others

No official statement by any organization was found relating to the quantitative relationship between blood glucose levels from daily monitoring and HbA1c levels. However, the American Diabetes Association (ADA) specifies treatment goals for both HbA1c and blood glucose levels. An ADA expert panel recently concluded, “There are insufficient data to determine accurately the relative contribution of fasting plasma glucose and postprandial plasma glucose to HbA1c.”¹³

Evidence summary

Four cohort studies of patients with diabetes have compared overall mean blood glucose levels with HbA1c levels.^1-4 All but one⁴ were limited to patients with type 1 diabetes. Study periods ranged from 1 to 6 months, and frequency of blood glucose measurement ranged from 2 to 4 times per day.

Correlation coefficients between mean blood glucose levels and HbA1c levels ranged from 0.71 to 0.86, implying that 50% to 74% of the variance in HbA1c is explained by the mean blood glucose (in each study, correlation was significant [P<.02]).

We found 5 studies comparing blood glucose measurements at specific times of day with HbA1c levels see (Table). Data from 3 studies comparing blood glucose values after lunchtime with those earlier in the day suggest that the lunchtime levels are more closely associated with HbA1c levels.^5,7,9 No consistent difference was shown between preprandial and postprandial blood glucose levels in their strength of association with HbA1c levels. In 1 of these studies, a blood glucose level of 150 mg/dL 2 hours after lunch predicted a HbA1c of 7% with 85% sensitivity and 85% specificity.⁷ One study provided only limited information on blood glucose–HbA1c correlations in relation to mealtimes but did report that the times of day at which the 2 were best correlated were in the periods from midnight to 5:00 AM and between noon and 3:00 PM.⁹ One study compared patients with type 1 and type 2 diabetes and found a higher correlation between blood glucose and HbA1c levels in the latter.⁶

The relationship between HbA1c and blood glucose levels is such that blood glucose levels from the preceding 30 days determine about 50% of the total HbA1c.¹⁰ This relationship may be altered by uremia, intake of vitamins C or E, and conditions that affect erythrocyte turnover.¹¹

It remains unclear whether management strategies that focus on minimizing HbA1c levels are optimal for prevention of diabetic complications.

Although HbA1c levels correlate with the risk of some complications, aspects of glycemia not reflected in the HbA1c level, such as the heights of glycemic “excursions” from the mean, may independently affect the risk of complications of diabetes.¹² If so, quantitative analysis of day-to-day blood glucose levels might yield a better estimation of the risk of diabetic complications than HbA1c levels.

TABLE
Correlation coefficients between blood glucose levels and hemoglobin A1c levels

Recommendations from others

No official statement by any organization was found relating to the quantitative relationship between blood glucose levels from daily monitoring and HbA1c levels. However, the American Diabetes Association (ADA) specifies treatment goals for both HbA1c and blood glucose levels. An ADA expert panel recently concluded, “There are insufficient data to determine accurately the relative contribution of fasting plasma glucose and postprandial plasma glucose to HbA1c.”¹³

Evidence summary

Four cohort studies of patients with diabetes have compared overall mean blood glucose levels with HbA1c levels.^1-4 All but one⁴ were limited to patients with type 1 diabetes. Study periods ranged from 1 to 6 months, and frequency of blood glucose measurement ranged from 2 to 4 times per day.

Correlation coefficients between mean blood glucose levels and HbA1c levels ranged from 0.71 to 0.86, implying that 50% to 74% of the variance in HbA1c is explained by the mean blood glucose (in each study, correlation was significant [P<.02]).

We found 5 studies comparing blood glucose measurements at specific times of day with HbA1c levels see (Table). Data from 3 studies comparing blood glucose values after lunchtime with those earlier in the day suggest that the lunchtime levels are more closely associated with HbA1c levels.^5,7,9 No consistent difference was shown between preprandial and postprandial blood glucose levels in their strength of association with HbA1c levels. In 1 of these studies, a blood glucose level of 150 mg/dL 2 hours after lunch predicted a HbA1c of 7% with 85% sensitivity and 85% specificity.⁷ One study provided only limited information on blood glucose–HbA1c correlations in relation to mealtimes but did report that the times of day at which the 2 were best correlated were in the periods from midnight to 5:00 AM and between noon and 3:00 PM.⁹ One study compared patients with type 1 and type 2 diabetes and found a higher correlation between blood glucose and HbA1c levels in the latter.⁶

The relationship between HbA1c and blood glucose levels is such that blood glucose levels from the preceding 30 days determine about 50% of the total HbA1c.¹⁰ This relationship may be altered by uremia, intake of vitamins C or E, and conditions that affect erythrocyte turnover.¹¹

It remains unclear whether management strategies that focus on minimizing HbA1c levels are optimal for prevention of diabetic complications.

Although HbA1c levels correlate with the risk of some complications, aspects of glycemia not reflected in the HbA1c level, such as the heights of glycemic “excursions” from the mean, may independently affect the risk of complications of diabetes.¹² If so, quantitative analysis of day-to-day blood glucose levels might yield a better estimation of the risk of diabetic complications than HbA1c levels.

TABLE
Correlation coefficients between blood glucose levels and hemoglobin A1c levels

Recommendations from others

No official statement by any organization was found relating to the quantitative relationship between blood glucose levels from daily monitoring and HbA1c levels. However, the American Diabetes Association (ADA) specifies treatment goals for both HbA1c and blood glucose levels. An ADA expert panel recently concluded, “There are insufficient data to determine accurately the relative contribution of fasting plasma glucose and postprandial plasma glucose to HbA1c.”¹³

EVIDENCE-BASED ANSWER

Asymptomatic term infants whose mothers received adequate intrapartum antibiotic prophylaxis (defined as intravenous penicillin or ampicillin at least 4 hours before delivery) for group B streptococcal disease do not need work-up or treatment (strength of recommendation [SOR]: B, based on retrospective, population-based study). These infants should be observed for 48 hours, but may be discharged after 24 hours in circumstances where close follow-up is available (SOR: D, based on expert opinion).

Symptomatic infants, premature infants (gestational age <35 weeks) of mothers who did not receive prophylaxis, and infants whose mothers had chorioamnionitis should receive a full evaluation (complete blood count, blood culture, and chest x-ray with or without a lumbar puncture) and an initial empiric antibiotic treatment with ampicillin or penicillin and gentamycin. If a term infant is not symptomatic and maternal antibiotic prophylaxis was not adequate, opinions differ as to whether to perform limited evaluation with empiric treatment or close observation (SOR: D, based on expert opinion). See Figure.

FIGURE
Management of infants born to mothers with group B streptococcal disease–positive cultures

Evidence summary

Intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal disease by 65% in the last decade.¹ A multicenter population-based study demonstrated that basing prophylaxis on screening cultures is twice as effective as risk stratification, a previously recommended strategy.²

Intrapartum prophylaxis of women who had positive group B streptococcal disease screening cultures at 35 weeks will prevent 70% of earlyonset disease and 89% of fatalities.^3,4 As demonstrated by multicenter retrospective studies, infants aged <35 weeks are at significantly higher risk of group B streptococcal disease than term infants (relative risk=1.5–2.07), and mortality for premature infants with early-onset disease (25%–30%) is substantially higher than for term infants with early-onset disease (2%–8%).^2,5

A large retrospective study demonstrated that infants who developed early-onset disease despite intrapartum prophylaxis developed the same clinical syndrome in the same time frame (78% of early-onset disease evident in first 24 hours and 96% by 48 hours) as infants whose mothers did not receive prophylaxis.⁶

The duration of adequate intrapartum antibiotic prophylaxis was initially set at 4 hours, based on a study measuring antibiotic penetration into amniotic fluid.⁷ A recent randomized trial, enrolling more than 4500 women, has confirmed this finding. The vertical transmission rate of group B streptococcal disease, as measured by neonatal colonization (as opposed to clinical illness), is 46% when antibiotic prophylaxis is started <1 hour before delivery, 2.9% when prophylaxis is given at 2 to 4 hours, and 1.2% when given at least 4 hours before delivery.⁸

Implementation of these guidelines is aided by the adoption of an institution-wide policy to support point of care decision-making.⁹ A retrospective study after the release of the 1996 Centers for Disease Control (CDC) guidelines concluded that hospitals with established group B streptococcal disease policies had significantly fewer cases of early-onset disease (P=.038).¹⁰

Recommendations from others

The 2002 Prevention of Perinatal Group B Streptococcal Disease Revised Guidelines from the CDC states: “a healthy-appearing infant whose mother received >4 hours of [intrapartum antibiotic prophylaxis] before delivery may be discharged home as early as 24 hours after delivery, assuming other discharge criteria have been met and that a person able to comply fully with instructions for home observation will be present … if these conditions are not met, the infant should remain in the hospital for at least 48 hours of observation and until criteria for discharge are achieved.”¹

These guidelines strongly support universal prenatal screening and the use of intrapartum antibiotic prophylaxis. Both the American Academy of Pediatrics and the American College Obstetrics and Gynecology have endorsed the CDC’s revised guidelines.

EVIDENCE-BASED ANSWER

Asymptomatic term infants whose mothers received adequate intrapartum antibiotic prophylaxis (defined as intravenous penicillin or ampicillin at least 4 hours before delivery) for group B streptococcal disease do not need work-up or treatment (strength of recommendation [SOR]: B, based on retrospective, population-based study). These infants should be observed for 48 hours, but may be discharged after 24 hours in circumstances where close follow-up is available (SOR: D, based on expert opinion).

Symptomatic infants, premature infants (gestational age <35 weeks) of mothers who did not receive prophylaxis, and infants whose mothers had chorioamnionitis should receive a full evaluation (complete blood count, blood culture, and chest x-ray with or without a lumbar puncture) and an initial empiric antibiotic treatment with ampicillin or penicillin and gentamycin. If a term infant is not symptomatic and maternal antibiotic prophylaxis was not adequate, opinions differ as to whether to perform limited evaluation with empiric treatment or close observation (SOR: D, based on expert opinion). See Figure.

FIGURE
Management of infants born to mothers with group B streptococcal disease–positive cultures

Evidence summary

Intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal disease by 65% in the last decade.¹ A multicenter population-based study demonstrated that basing prophylaxis on screening cultures is twice as effective as risk stratification, a previously recommended strategy.²

Intrapartum prophylaxis of women who had positive group B streptococcal disease screening cultures at 35 weeks will prevent 70% of earlyonset disease and 89% of fatalities.^3,4 As demonstrated by multicenter retrospective studies, infants aged <35 weeks are at significantly higher risk of group B streptococcal disease than term infants (relative risk=1.5–2.07), and mortality for premature infants with early-onset disease (25%–30%) is substantially higher than for term infants with early-onset disease (2%–8%).^2,5

A large retrospective study demonstrated that infants who developed early-onset disease despite intrapartum prophylaxis developed the same clinical syndrome in the same time frame (78% of early-onset disease evident in first 24 hours and 96% by 48 hours) as infants whose mothers did not receive prophylaxis.⁶

The duration of adequate intrapartum antibiotic prophylaxis was initially set at 4 hours, based on a study measuring antibiotic penetration into amniotic fluid.⁷ A recent randomized trial, enrolling more than 4500 women, has confirmed this finding. The vertical transmission rate of group B streptococcal disease, as measured by neonatal colonization (as opposed to clinical illness), is 46% when antibiotic prophylaxis is started <1 hour before delivery, 2.9% when prophylaxis is given at 2 to 4 hours, and 1.2% when given at least 4 hours before delivery.⁸

Implementation of these guidelines is aided by the adoption of an institution-wide policy to support point of care decision-making.⁹ A retrospective study after the release of the 1996 Centers for Disease Control (CDC) guidelines concluded that hospitals with established group B streptococcal disease policies had significantly fewer cases of early-onset disease (P=.038).¹⁰

Recommendations from others

The 2002 Prevention of Perinatal Group B Streptococcal Disease Revised Guidelines from the CDC states: “a healthy-appearing infant whose mother received >4 hours of [intrapartum antibiotic prophylaxis] before delivery may be discharged home as early as 24 hours after delivery, assuming other discharge criteria have been met and that a person able to comply fully with instructions for home observation will be present … if these conditions are not met, the infant should remain in the hospital for at least 48 hours of observation and until criteria for discharge are achieved.”¹

These guidelines strongly support universal prenatal screening and the use of intrapartum antibiotic prophylaxis. Both the American Academy of Pediatrics and the American College Obstetrics and Gynecology have endorsed the CDC’s revised guidelines.

EVIDENCE-BASED ANSWER

Asymptomatic term infants whose mothers received adequate intrapartum antibiotic prophylaxis (defined as intravenous penicillin or ampicillin at least 4 hours before delivery) for group B streptococcal disease do not need work-up or treatment (strength of recommendation [SOR]: B, based on retrospective, population-based study). These infants should be observed for 48 hours, but may be discharged after 24 hours in circumstances where close follow-up is available (SOR: D, based on expert opinion).

Symptomatic infants, premature infants (gestational age <35 weeks) of mothers who did not receive prophylaxis, and infants whose mothers had chorioamnionitis should receive a full evaluation (complete blood count, blood culture, and chest x-ray with or without a lumbar puncture) and an initial empiric antibiotic treatment with ampicillin or penicillin and gentamycin. If a term infant is not symptomatic and maternal antibiotic prophylaxis was not adequate, opinions differ as to whether to perform limited evaluation with empiric treatment or close observation (SOR: D, based on expert opinion). See Figure.

FIGURE
Management of infants born to mothers with group B streptococcal disease–positive cultures

Evidence summary

Intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal disease by 65% in the last decade.¹ A multicenter population-based study demonstrated that basing prophylaxis on screening cultures is twice as effective as risk stratification, a previously recommended strategy.²

Intrapartum prophylaxis of women who had positive group B streptococcal disease screening cultures at 35 weeks will prevent 70% of earlyonset disease and 89% of fatalities.^3,4 As demonstrated by multicenter retrospective studies, infants aged <35 weeks are at significantly higher risk of group B streptococcal disease than term infants (relative risk=1.5–2.07), and mortality for premature infants with early-onset disease (25%–30%) is substantially higher than for term infants with early-onset disease (2%–8%).^2,5

A large retrospective study demonstrated that infants who developed early-onset disease despite intrapartum prophylaxis developed the same clinical syndrome in the same time frame (78% of early-onset disease evident in first 24 hours and 96% by 48 hours) as infants whose mothers did not receive prophylaxis.⁶

The duration of adequate intrapartum antibiotic prophylaxis was initially set at 4 hours, based on a study measuring antibiotic penetration into amniotic fluid.⁷ A recent randomized trial, enrolling more than 4500 women, has confirmed this finding. The vertical transmission rate of group B streptococcal disease, as measured by neonatal colonization (as opposed to clinical illness), is 46% when antibiotic prophylaxis is started <1 hour before delivery, 2.9% when prophylaxis is given at 2 to 4 hours, and 1.2% when given at least 4 hours before delivery.⁸

Implementation of these guidelines is aided by the adoption of an institution-wide policy to support point of care decision-making.⁹ A retrospective study after the release of the 1996 Centers for Disease Control (CDC) guidelines concluded that hospitals with established group B streptococcal disease policies had significantly fewer cases of early-onset disease (P=.038).¹⁰

Recommendations from others

The 2002 Prevention of Perinatal Group B Streptococcal Disease Revised Guidelines from the CDC states: “a healthy-appearing infant whose mother received >4 hours of [intrapartum antibiotic prophylaxis] before delivery may be discharged home as early as 24 hours after delivery, assuming other discharge criteria have been met and that a person able to comply fully with instructions for home observation will be present … if these conditions are not met, the infant should remain in the hospital for at least 48 hours of observation and until criteria for discharge are achieved.”¹

These guidelines strongly support universal prenatal screening and the use of intrapartum antibiotic prophylaxis. Both the American Academy of Pediatrics and the American College Obstetrics and Gynecology have endorsed the CDC’s revised guidelines.

Evidence summary

Several randomized controlled trials and a meta-analysis demonstrated that the children most likely to benefit from tympanostomy tubes are those more than 6 months old with middle-ear effusion who have had 3 or more episodes of acute otitis media in 6 months, or 4 or more episodes in 12 months.^1-4 Data are inadequate to determine the lowest rate of recurrence that would suggest a benefit from tube placement.

A meta-analysis of 5 randomized trials comparing no surgery with placement of tubes for recurrent acute otitis media with or without middle-ear effusion showed that the placement of tubes resulted in a mean absolute decrease in acute otitis media incidence of 1.0 per year (95% confidence interval [CI], 0.4–1.6), and a decrease in the prevalence of middle-ear effusion by 115 days per year (95% CI, 11–220).⁴ The benefit of tubes for recurrent acute otitis media was demonstrated only in studies in which middle-ear effusion was present:^2,3 one found 3.01 (95% CI, 2.18–3.84) fewer acute episodes per year;^1,4 the other found 2.27 (95% CI, 1.03–3.51) fewer.^2,4

One randomized controlled trial of 264 children, aged 7 to 35 months, with a history of recurrent acute otitis media but free of middle-ear effusion, compared tubes with medical therapy and found no difference in recurrence over 2 years.³ The medical therapy arm received prophylaxis with either amoxicillin or placebo. The amoxicillin arm had 0.6 fewer episodes of acute otitis media per year compared with the other 2, a statistically significant 40% decrease (relative risk reduction=0.4).³

The average time with otitis media of any type (acute otitis media, otitis media with effusion, or ottorhea) also decreased—15.0% in the placebo group, 10.0% in the amoxicillin group, and 6.6% in the tympanostomy tube group (amoxicillin vs. placebo, P=.03; tubes vs. placebo, P<.001).³ Higher dropout rates occurred in the amoxicillin and medical treatment groups.³

In prospective studies of patients receiving tubes for recurrent acute otitis media and otitis media with effusion, measures of quality of life—physical suffering, emotional distress, activity limitation, hearing loss, speech development, caregiver concern/worry, parental post-tube satisfaction,^4,5,6 and an ear symptom score⁶ —improved after tube placement. Within several weeks of tube placement, 79% of children had improved quality of life, 17% had trivial change, and 4% were worse.⁴

A meta-analysis reporting sequelae of tympanostomy tubes found an absolute complication rate of 26% for transient otorrhea and 4% for chronic otorrhea.⁴

Compared with nonsurgical treatment, complication rates for tube placement were reported in 0.7% of surgically treated ears.⁷ Complications included:

• tympanosclerosis (relative risk [RR]=3.5 [95% CI, 2.6–4.9])
• focal atrophy (RR=1.7 [95% CI, 1.1–2.7])
• perforation (RR=3.5 [95% CI, 1.5–7.1])
  • 2% with short-term tubes
  • 16% with long-term tubes
• cholesteatoma (RR=2.6 [95% CI, 1.5–4.4]).

Recommendations from others

The Institute for Clinical Systems Improvement 2001 guidelines for recurrent acute otitis media treatment in children recommends initial antibiotic prophylaxis with amoxicillin (20 mg/kg/day) for 2 to 6 months (based on randomized controlled trial data). If there are 2 recurrences of acute otitis media during that time, then referral to an otorhinolaryngologist for possible tympanostomy tube placement is recommended.⁸

Evidence summary

Several randomized controlled trials and a meta-analysis demonstrated that the children most likely to benefit from tympanostomy tubes are those more than 6 months old with middle-ear effusion who have had 3 or more episodes of acute otitis media in 6 months, or 4 or more episodes in 12 months.^1-4 Data are inadequate to determine the lowest rate of recurrence that would suggest a benefit from tube placement.

A meta-analysis of 5 randomized trials comparing no surgery with placement of tubes for recurrent acute otitis media with or without middle-ear effusion showed that the placement of tubes resulted in a mean absolute decrease in acute otitis media incidence of 1.0 per year (95% confidence interval [CI], 0.4–1.6), and a decrease in the prevalence of middle-ear effusion by 115 days per year (95% CI, 11–220).⁴ The benefit of tubes for recurrent acute otitis media was demonstrated only in studies in which middle-ear effusion was present:^2,3 one found 3.01 (95% CI, 2.18–3.84) fewer acute episodes per year;^1,4 the other found 2.27 (95% CI, 1.03–3.51) fewer.^2,4

One randomized controlled trial of 264 children, aged 7 to 35 months, with a history of recurrent acute otitis media but free of middle-ear effusion, compared tubes with medical therapy and found no difference in recurrence over 2 years.³ The medical therapy arm received prophylaxis with either amoxicillin or placebo. The amoxicillin arm had 0.6 fewer episodes of acute otitis media per year compared with the other 2, a statistically significant 40% decrease (relative risk reduction=0.4).³

The average time with otitis media of any type (acute otitis media, otitis media with effusion, or ottorhea) also decreased—15.0% in the placebo group, 10.0% in the amoxicillin group, and 6.6% in the tympanostomy tube group (amoxicillin vs. placebo, P=.03; tubes vs. placebo, P<.001).³ Higher dropout rates occurred in the amoxicillin and medical treatment groups.³

In prospective studies of patients receiving tubes for recurrent acute otitis media and otitis media with effusion, measures of quality of life—physical suffering, emotional distress, activity limitation, hearing loss, speech development, caregiver concern/worry, parental post-tube satisfaction,^4,5,6 and an ear symptom score⁶ —improved after tube placement. Within several weeks of tube placement, 79% of children had improved quality of life, 17% had trivial change, and 4% were worse.⁴

A meta-analysis reporting sequelae of tympanostomy tubes found an absolute complication rate of 26% for transient otorrhea and 4% for chronic otorrhea.⁴

Compared with nonsurgical treatment, complication rates for tube placement were reported in 0.7% of surgically treated ears.⁷ Complications included:

• tympanosclerosis (relative risk [RR]=3.5 [95% CI, 2.6–4.9])
• focal atrophy (RR=1.7 [95% CI, 1.1–2.7])
• perforation (RR=3.5 [95% CI, 1.5–7.1])
  • 2% with short-term tubes
  • 16% with long-term tubes
• cholesteatoma (RR=2.6 [95% CI, 1.5–4.4]).

Recommendations from others

The Institute for Clinical Systems Improvement 2001 guidelines for recurrent acute otitis media treatment in children recommends initial antibiotic prophylaxis with amoxicillin (20 mg/kg/day) for 2 to 6 months (based on randomized controlled trial data). If there are 2 recurrences of acute otitis media during that time, then referral to an otorhinolaryngologist for possible tympanostomy tube placement is recommended.⁸

Evidence summary

Several randomized controlled trials and a meta-analysis demonstrated that the children most likely to benefit from tympanostomy tubes are those more than 6 months old with middle-ear effusion who have had 3 or more episodes of acute otitis media in 6 months, or 4 or more episodes in 12 months.^1-4 Data are inadequate to determine the lowest rate of recurrence that would suggest a benefit from tube placement.

A meta-analysis of 5 randomized trials comparing no surgery with placement of tubes for recurrent acute otitis media with or without middle-ear effusion showed that the placement of tubes resulted in a mean absolute decrease in acute otitis media incidence of 1.0 per year (95% confidence interval [CI], 0.4–1.6), and a decrease in the prevalence of middle-ear effusion by 115 days per year (95% CI, 11–220).⁴ The benefit of tubes for recurrent acute otitis media was demonstrated only in studies in which middle-ear effusion was present:^2,3 one found 3.01 (95% CI, 2.18–3.84) fewer acute episodes per year;^1,4 the other found 2.27 (95% CI, 1.03–3.51) fewer.^2,4

One randomized controlled trial of 264 children, aged 7 to 35 months, with a history of recurrent acute otitis media but free of middle-ear effusion, compared tubes with medical therapy and found no difference in recurrence over 2 years.³ The medical therapy arm received prophylaxis with either amoxicillin or placebo. The amoxicillin arm had 0.6 fewer episodes of acute otitis media per year compared with the other 2, a statistically significant 40% decrease (relative risk reduction=0.4).³

The average time with otitis media of any type (acute otitis media, otitis media with effusion, or ottorhea) also decreased—15.0% in the placebo group, 10.0% in the amoxicillin group, and 6.6% in the tympanostomy tube group (amoxicillin vs. placebo, P=.03; tubes vs. placebo, P<.001).³ Higher dropout rates occurred in the amoxicillin and medical treatment groups.³

In prospective studies of patients receiving tubes for recurrent acute otitis media and otitis media with effusion, measures of quality of life—physical suffering, emotional distress, activity limitation, hearing loss, speech development, caregiver concern/worry, parental post-tube satisfaction,^4,5,6 and an ear symptom score⁶ —improved after tube placement. Within several weeks of tube placement, 79% of children had improved quality of life, 17% had trivial change, and 4% were worse.⁴

A meta-analysis reporting sequelae of tympanostomy tubes found an absolute complication rate of 26% for transient otorrhea and 4% for chronic otorrhea.⁴

Compared with nonsurgical treatment, complication rates for tube placement were reported in 0.7% of surgically treated ears.⁷ Complications included:

• tympanosclerosis (relative risk [RR]=3.5 [95% CI, 2.6–4.9])
• focal atrophy (RR=1.7 [95% CI, 1.1–2.7])
• perforation (RR=3.5 [95% CI, 1.5–7.1])
  • 2% with short-term tubes
  • 16% with long-term tubes
• cholesteatoma (RR=2.6 [95% CI, 1.5–4.4]).

Recommendations from others

The Institute for Clinical Systems Improvement 2001 guidelines for recurrent acute otitis media treatment in children recommends initial antibiotic prophylaxis with amoxicillin (20 mg/kg/day) for 2 to 6 months (based on randomized controlled trial data). If there are 2 recurrences of acute otitis media during that time, then referral to an otorhinolaryngologist for possible tympanostomy tube placement is recommended.⁸