Sarah Safranek, MLIS

Evidence summary

Although no studies identify the optimal age or frequency of screening,¹ the American Academy of Pediatrics (AAP) recommends surveillance for developmental delays (including speech and language delay [SLD]) at every preventive visit and additional developmental screening at 9, 18, 24, and 30 months.²

No single standardized tool exists to screen for SLDs; no research compares the tools against each other or offers clear evidence of how sensitive they are.¹ Commonly used brief screening tools include Ages and Stages Parent Questionnaire (ASQ) (1-66 months of age), Denver Developmental Screen II (1-66 months), Early Language Milestone Scale (1-36 months), Clinical Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (<24 months), Infant Developmental Inventory and Child Development Review (1-66 months), and the Fluharty Preschool Speech and Language Screening Tests (3-5 years).

When a child screens positive for speech and language delay
When an SLD is recognized, experts recommend a history and physical examination to evaluate for common causes (TABLE). A detailed history should focus on family, social, and environmental aspects affecting speech. A comprehensive physical examination should evaluate the child’s interaction with the examiner and family members, pronunciation of sounds and words, and include a careful examination of the face, external ears and tympanic membranes, nose, palate, teeth, tongue, and neck.^3,4

Experts recommend full audiologic assessment and vision testing for all children with SLD and an electroencephalogram or chromosomal studies if appropriate. When no cause for the SLD is found, experts recommend consulting a speech pathologist. Consultation with an audiologist, psychologist, neurologist, occupational therapist, or social worker also may be helpful.^1-4

TABLE
Common causes of speech and language delays

How effective are speech and language interventions?
A systematic review of 14 RCTs evaluated speech and language therapy interventions ranging from 3 to 6 months’ duration in pre-school children. Investigators reported significant improvements in speech and language outcomes, including articulation, phonation and syntax, and expressive and receptive language with the interventions. Individual studies were limited by small size, heterogeneity, and varied measures of short-term outcomes.¹

A Cochrane meta-analysis of 25 RCTs (N=1539 children, of whom 986 were <5 years) found that speech and language therapy produced similar improvements for preschool and elementary school children. Therapy improved phonological delays significantly (standard mean difference [SMD]=0.44; 95% confidence interval [CI], 0.01-0.86), and vocabulary difficulties even more (SMD=0.89; 95% CI, 0.21-1.56). However, in this review, therapy didn’t significantly affect receptive speech difficulties (SMD=?0.04; 95% CI, ?0.64 to 0.56).

The analysis didn’t evaluate whether specific age groups would respond better to therapy.⁵ No studies evaluated long-term effectiveness or possible harms associated with screening or intervention.⁴

Recommendations

The AAP Council on Children with Disabilities, Section on Developmental Behavioral Pediatrics recommends general developmental surveillance at every well-child visit for children from birth through 3 years of age and more formal screening tests at the 9-, 18-, and 30-month visits. The AAP doesn’t recommend a specific screening test, however.²

The US Preventive Services Task Force found insufficient evidence that brief formal screening instruments accurately identify pre-school children who would benefit from further evaluation and intervention, but found fair evidence that interventions improve speech in the short term.⁶

Evidence summary

Although no studies identify the optimal age or frequency of screening,¹ the American Academy of Pediatrics (AAP) recommends surveillance for developmental delays (including speech and language delay [SLD]) at every preventive visit and additional developmental screening at 9, 18, 24, and 30 months.²

No single standardized tool exists to screen for SLDs; no research compares the tools against each other or offers clear evidence of how sensitive they are.¹ Commonly used brief screening tools include Ages and Stages Parent Questionnaire (ASQ) (1-66 months of age), Denver Developmental Screen II (1-66 months), Early Language Milestone Scale (1-36 months), Clinical Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (<24 months), Infant Developmental Inventory and Child Development Review (1-66 months), and the Fluharty Preschool Speech and Language Screening Tests (3-5 years).

When a child screens positive for speech and language delay
When an SLD is recognized, experts recommend a history and physical examination to evaluate for common causes (TABLE). A detailed history should focus on family, social, and environmental aspects affecting speech. A comprehensive physical examination should evaluate the child’s interaction with the examiner and family members, pronunciation of sounds and words, and include a careful examination of the face, external ears and tympanic membranes, nose, palate, teeth, tongue, and neck.^3,4

Experts recommend full audiologic assessment and vision testing for all children with SLD and an electroencephalogram or chromosomal studies if appropriate. When no cause for the SLD is found, experts recommend consulting a speech pathologist. Consultation with an audiologist, psychologist, neurologist, occupational therapist, or social worker also may be helpful.^1-4

TABLE
Common causes of speech and language delays

How effective are speech and language interventions?
A systematic review of 14 RCTs evaluated speech and language therapy interventions ranging from 3 to 6 months’ duration in pre-school children. Investigators reported significant improvements in speech and language outcomes, including articulation, phonation and syntax, and expressive and receptive language with the interventions. Individual studies were limited by small size, heterogeneity, and varied measures of short-term outcomes.¹

A Cochrane meta-analysis of 25 RCTs (N=1539 children, of whom 986 were <5 years) found that speech and language therapy produced similar improvements for preschool and elementary school children. Therapy improved phonological delays significantly (standard mean difference [SMD]=0.44; 95% confidence interval [CI], 0.01-0.86), and vocabulary difficulties even more (SMD=0.89; 95% CI, 0.21-1.56). However, in this review, therapy didn’t significantly affect receptive speech difficulties (SMD=?0.04; 95% CI, ?0.64 to 0.56).

The analysis didn’t evaluate whether specific age groups would respond better to therapy.⁵ No studies evaluated long-term effectiveness or possible harms associated with screening or intervention.⁴

Recommendations

The AAP Council on Children with Disabilities, Section on Developmental Behavioral Pediatrics recommends general developmental surveillance at every well-child visit for children from birth through 3 years of age and more formal screening tests at the 9-, 18-, and 30-month visits. The AAP doesn’t recommend a specific screening test, however.²

The US Preventive Services Task Force found insufficient evidence that brief formal screening instruments accurately identify pre-school children who would benefit from further evaluation and intervention, but found fair evidence that interventions improve speech in the short term.⁶

Evidence summary

Although no studies identify the optimal age or frequency of screening,¹ the American Academy of Pediatrics (AAP) recommends surveillance for developmental delays (including speech and language delay [SLD]) at every preventive visit and additional developmental screening at 9, 18, 24, and 30 months.²

No single standardized tool exists to screen for SLDs; no research compares the tools against each other or offers clear evidence of how sensitive they are.¹ Commonly used brief screening tools include Ages and Stages Parent Questionnaire (ASQ) (1-66 months of age), Denver Developmental Screen II (1-66 months), Early Language Milestone Scale (1-36 months), Clinical Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (<24 months), Infant Developmental Inventory and Child Development Review (1-66 months), and the Fluharty Preschool Speech and Language Screening Tests (3-5 years).

When a child screens positive for speech and language delay
When an SLD is recognized, experts recommend a history and physical examination to evaluate for common causes (TABLE). A detailed history should focus on family, social, and environmental aspects affecting speech. A comprehensive physical examination should evaluate the child’s interaction with the examiner and family members, pronunciation of sounds and words, and include a careful examination of the face, external ears and tympanic membranes, nose, palate, teeth, tongue, and neck.^3,4

Experts recommend full audiologic assessment and vision testing for all children with SLD and an electroencephalogram or chromosomal studies if appropriate. When no cause for the SLD is found, experts recommend consulting a speech pathologist. Consultation with an audiologist, psychologist, neurologist, occupational therapist, or social worker also may be helpful.^1-4

TABLE
Common causes of speech and language delays

How effective are speech and language interventions?
A systematic review of 14 RCTs evaluated speech and language therapy interventions ranging from 3 to 6 months’ duration in pre-school children. Investigators reported significant improvements in speech and language outcomes, including articulation, phonation and syntax, and expressive and receptive language with the interventions. Individual studies were limited by small size, heterogeneity, and varied measures of short-term outcomes.¹

A Cochrane meta-analysis of 25 RCTs (N=1539 children, of whom 986 were <5 years) found that speech and language therapy produced similar improvements for preschool and elementary school children. Therapy improved phonological delays significantly (standard mean difference [SMD]=0.44; 95% confidence interval [CI], 0.01-0.86), and vocabulary difficulties even more (SMD=0.89; 95% CI, 0.21-1.56). However, in this review, therapy didn’t significantly affect receptive speech difficulties (SMD=?0.04; 95% CI, ?0.64 to 0.56).

The analysis didn’t evaluate whether specific age groups would respond better to therapy.⁵ No studies evaluated long-term effectiveness or possible harms associated with screening or intervention.⁴

Recommendations

The AAP Council on Children with Disabilities, Section on Developmental Behavioral Pediatrics recommends general developmental surveillance at every well-child visit for children from birth through 3 years of age and more formal screening tests at the 9-, 18-, and 30-month visits. The AAP doesn’t recommend a specific screening test, however.²

The US Preventive Services Task Force found insufficient evidence that brief formal screening instruments accurately identify pre-school children who would benefit from further evaluation and intervention, but found fair evidence that interventions improve speech in the short term.⁶

Evidence summary

A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).¹

Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).²

TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials^1,2

Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.¹ A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.^3,4

Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.^1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)¹

Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.^3,5

Other comparisons that found no significant difference in effectiveness included:

• 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid^1,2
• 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid⁶
• 1 RCT (N=43) that compared topical metronidazole with topical permethrin¹
• 1 RCT (N=40) that compared oral metronidazole with oral tetracycline¹
• 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily⁴
• 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.⁷

Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).¹ Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).⁴

Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).² Another case series with 17 patients reported improvements with photodynamic therapy with red ight.⁸

General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.⁹ Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.^1,2

Recommendations

The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.

The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.¹⁰

Evidence summary

A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).¹

Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).²

TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials^1,2

Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.¹ A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.^3,4

Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.^1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)¹

Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.^3,5

Other comparisons that found no significant difference in effectiveness included:

• 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid^1,2
• 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid⁶
• 1 RCT (N=43) that compared topical metronidazole with topical permethrin¹
• 1 RCT (N=40) that compared oral metronidazole with oral tetracycline¹
• 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily⁴
• 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.⁷

Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).¹ Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).⁴

Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).² Another case series with 17 patients reported improvements with photodynamic therapy with red ight.⁸

General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.⁹ Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.^1,2

Recommendations

The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.

The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.¹⁰

Evidence summary

A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).¹

Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).²

TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials^1,2

Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.¹ A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.^3,4

Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.^1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)¹

Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.^3,5

Other comparisons that found no significant difference in effectiveness included:

• 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid^1,2
• 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid⁶
• 1 RCT (N=43) that compared topical metronidazole with topical permethrin¹
• 1 RCT (N=40) that compared oral metronidazole with oral tetracycline¹
• 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily⁴
• 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.⁷

Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).¹ Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).⁴

Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).² Another case series with 17 patients reported improvements with photodynamic therapy with red ight.⁸

General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.⁹ Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.^1,2

Recommendations

The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.

The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.¹⁰

Evidence summary

A systematic review of 3 RCTs with a total of 649 participants evaluated office spirometry as a motivational tool to improve quit rates by comparing spirometry plus cessation advice with cessation advice alone. All participants were men and women 19 to 75 years of age recruited from outpatient clinics.¹

In 1 trial, the intervention group received repeated counseling at 4 visits and underwent spirometry; the control group had 1 counseling session and was given a brochure. In the other 2 trials, the intervention group had both carbon monoxide measurements and spirometry, and all participants received more extensive counseling, including cessation skills training.

At 9 to 12 months’ follow-up, quit rates ranged from 6% to 24% in the intervention groups vs 5% to 14% in the control groups (not significantly different).¹

A subsequent study randomized 221 smokers to receive either spirometry plus brief cessation advice or advice alone. Researchers recruited patients 15 to 80 years of age who were willing to quit smoking from 16 general practice clinics in Belgium. Fifty-one percent of patients in both groups used nicotine replacement therapy (a larger percentage than is typical in studies done in the United States). At 6, 12, and 24 months, 5%, 2%, and 5% more smokers, respectively, from the spirometry group quit smoking compared with the control group, but this difference was not significant.²

Reporting spirometry results in terms of lung age may spur quitting
One RCT found significantly improved quit rates when patients who smoked were given their office spirometry results in terms of “lung age” (the age of an average healthy person with similar spirometry results) rather than as forced expiratory volume in 1 second (FEV1). Investigators performed office spirometry and gave smoking cessation advice to 561 smokers older than 35 years who were recruited from 5 general practices. They randomized patients to receive their spirometry results as either lung age or FEV1 and recorded quit rates at 12 months (smoking cessation was verified by measuring blood levels of carbon monoxide).

Patients whose spirometry results were reported as lung age were significantly more likely to quit than smokers whose results were given as FEV1 (13.6% vs 6.4%; P=.005; number needed to treat [NNT]=14 smokers counseled using lung age to cause 1 more patient to quit). Smokers with normal lung ages were no more likely to quit than smokers with abnormal results.³

Abnormal results also may be a motivator
However, 3 prospective cohort studies demonstrated that patients with abnormal spirometry results were more likely to quit than patients with normal spirometry. In the first study, 4494 patients with at least 10 pack-years of smoking from 10 outpatient chest clinics in Poland underwent spirometry and were counseled to quit smoking; 1177 had abnormal spirometry results.

One year later, 16.3% of smokers with abnormal results had quit smoking, compared with 12% in the group with normal spirometry (P=.0003; NNT=23).⁴

The second study, also at outpatient chest clinics in Poland, evaluated spirometry plus cessation advice among 558 smokers, 297 of whom had abnormal spirometry results. At 1 year, 10.6% of patients with abnormal results had quit, compared with 8.4% of patients with normal lung function. A subgroup of 109 patients with moderate to severe airflow limitation showed significantly higher quit rates when compared with patients with mildly abnormal spirometry (16.5% vs 6.4%; P<.0001; NNT=10).⁵

In the third study, 6 primary care sites in Sweden provided spirometry and brief cessation advice to 445 smokers, 119 of whom were found to have abnormal lung function. At 3-year follow-up, 29% of patients with abnormal lung function had quit smoking, compared with 14% of patients with normal lung function (P=.001; NNT=7). Forty-five smokers with mildly abnormal lung function were recruited from this study to participate in another study, which may have biased the results toward higher quit rates among smokers with worse spirometry results.⁶

Recommendations

The US Preventive Services Task Force recommends against using spirometry to screen for chronic obstructive pulmonary disease, but advocates screening all adults for tobacco use and encouraging cessation.⁷

The authors of a Cochrane review found insufficient evidence to recommend using biomedical risk assessment (carbon monoxide blood levels, spirometry, genetic testing for alpha-1 antitrypsin deficiency) as a smoking cessation aid.⁸

Evidence summary

A systematic review of 3 RCTs with a total of 649 participants evaluated office spirometry as a motivational tool to improve quit rates by comparing spirometry plus cessation advice with cessation advice alone. All participants were men and women 19 to 75 years of age recruited from outpatient clinics.¹

In 1 trial, the intervention group received repeated counseling at 4 visits and underwent spirometry; the control group had 1 counseling session and was given a brochure. In the other 2 trials, the intervention group had both carbon monoxide measurements and spirometry, and all participants received more extensive counseling, including cessation skills training.

At 9 to 12 months’ follow-up, quit rates ranged from 6% to 24% in the intervention groups vs 5% to 14% in the control groups (not significantly different).¹

A subsequent study randomized 221 smokers to receive either spirometry plus brief cessation advice or advice alone. Researchers recruited patients 15 to 80 years of age who were willing to quit smoking from 16 general practice clinics in Belgium. Fifty-one percent of patients in both groups used nicotine replacement therapy (a larger percentage than is typical in studies done in the United States). At 6, 12, and 24 months, 5%, 2%, and 5% more smokers, respectively, from the spirometry group quit smoking compared with the control group, but this difference was not significant.²

Reporting spirometry results in terms of lung age may spur quitting
One RCT found significantly improved quit rates when patients who smoked were given their office spirometry results in terms of “lung age” (the age of an average healthy person with similar spirometry results) rather than as forced expiratory volume in 1 second (FEV1). Investigators performed office spirometry and gave smoking cessation advice to 561 smokers older than 35 years who were recruited from 5 general practices. They randomized patients to receive their spirometry results as either lung age or FEV1 and recorded quit rates at 12 months (smoking cessation was verified by measuring blood levels of carbon monoxide).

Patients whose spirometry results were reported as lung age were significantly more likely to quit than smokers whose results were given as FEV1 (13.6% vs 6.4%; P=.005; number needed to treat [NNT]=14 smokers counseled using lung age to cause 1 more patient to quit). Smokers with normal lung ages were no more likely to quit than smokers with abnormal results.³

Abnormal results also may be a motivator
However, 3 prospective cohort studies demonstrated that patients with abnormal spirometry results were more likely to quit than patients with normal spirometry. In the first study, 4494 patients with at least 10 pack-years of smoking from 10 outpatient chest clinics in Poland underwent spirometry and were counseled to quit smoking; 1177 had abnormal spirometry results.

One year later, 16.3% of smokers with abnormal results had quit smoking, compared with 12% in the group with normal spirometry (P=.0003; NNT=23).⁴

The second study, also at outpatient chest clinics in Poland, evaluated spirometry plus cessation advice among 558 smokers, 297 of whom had abnormal spirometry results. At 1 year, 10.6% of patients with abnormal results had quit, compared with 8.4% of patients with normal lung function. A subgroup of 109 patients with moderate to severe airflow limitation showed significantly higher quit rates when compared with patients with mildly abnormal spirometry (16.5% vs 6.4%; P<.0001; NNT=10).⁵

In the third study, 6 primary care sites in Sweden provided spirometry and brief cessation advice to 445 smokers, 119 of whom were found to have abnormal lung function. At 3-year follow-up, 29% of patients with abnormal lung function had quit smoking, compared with 14% of patients with normal lung function (P=.001; NNT=7). Forty-five smokers with mildly abnormal lung function were recruited from this study to participate in another study, which may have biased the results toward higher quit rates among smokers with worse spirometry results.⁶

Recommendations

The US Preventive Services Task Force recommends against using spirometry to screen for chronic obstructive pulmonary disease, but advocates screening all adults for tobacco use and encouraging cessation.⁷

The authors of a Cochrane review found insufficient evidence to recommend using biomedical risk assessment (carbon monoxide blood levels, spirometry, genetic testing for alpha-1 antitrypsin deficiency) as a smoking cessation aid.⁸

Evidence summary

A systematic review of 3 RCTs with a total of 649 participants evaluated office spirometry as a motivational tool to improve quit rates by comparing spirometry plus cessation advice with cessation advice alone. All participants were men and women 19 to 75 years of age recruited from outpatient clinics.¹

In 1 trial, the intervention group received repeated counseling at 4 visits and underwent spirometry; the control group had 1 counseling session and was given a brochure. In the other 2 trials, the intervention group had both carbon monoxide measurements and spirometry, and all participants received more extensive counseling, including cessation skills training.

At 9 to 12 months’ follow-up, quit rates ranged from 6% to 24% in the intervention groups vs 5% to 14% in the control groups (not significantly different).¹

A subsequent study randomized 221 smokers to receive either spirometry plus brief cessation advice or advice alone. Researchers recruited patients 15 to 80 years of age who were willing to quit smoking from 16 general practice clinics in Belgium. Fifty-one percent of patients in both groups used nicotine replacement therapy (a larger percentage than is typical in studies done in the United States). At 6, 12, and 24 months, 5%, 2%, and 5% more smokers, respectively, from the spirometry group quit smoking compared with the control group, but this difference was not significant.²

Reporting spirometry results in terms of lung age may spur quitting
One RCT found significantly improved quit rates when patients who smoked were given their office spirometry results in terms of “lung age” (the age of an average healthy person with similar spirometry results) rather than as forced expiratory volume in 1 second (FEV1). Investigators performed office spirometry and gave smoking cessation advice to 561 smokers older than 35 years who were recruited from 5 general practices. They randomized patients to receive their spirometry results as either lung age or FEV1 and recorded quit rates at 12 months (smoking cessation was verified by measuring blood levels of carbon monoxide).

Patients whose spirometry results were reported as lung age were significantly more likely to quit than smokers whose results were given as FEV1 (13.6% vs 6.4%; P=.005; number needed to treat [NNT]=14 smokers counseled using lung age to cause 1 more patient to quit). Smokers with normal lung ages were no more likely to quit than smokers with abnormal results.³

Abnormal results also may be a motivator
However, 3 prospective cohort studies demonstrated that patients with abnormal spirometry results were more likely to quit than patients with normal spirometry. In the first study, 4494 patients with at least 10 pack-years of smoking from 10 outpatient chest clinics in Poland underwent spirometry and were counseled to quit smoking; 1177 had abnormal spirometry results.

One year later, 16.3% of smokers with abnormal results had quit smoking, compared with 12% in the group with normal spirometry (P=.0003; NNT=23).⁴

The second study, also at outpatient chest clinics in Poland, evaluated spirometry plus cessation advice among 558 smokers, 297 of whom had abnormal spirometry results. At 1 year, 10.6% of patients with abnormal results had quit, compared with 8.4% of patients with normal lung function. A subgroup of 109 patients with moderate to severe airflow limitation showed significantly higher quit rates when compared with patients with mildly abnormal spirometry (16.5% vs 6.4%; P<.0001; NNT=10).⁵

In the third study, 6 primary care sites in Sweden provided spirometry and brief cessation advice to 445 smokers, 119 of whom were found to have abnormal lung function. At 3-year follow-up, 29% of patients with abnormal lung function had quit smoking, compared with 14% of patients with normal lung function (P=.001; NNT=7). Forty-five smokers with mildly abnormal lung function were recruited from this study to participate in another study, which may have biased the results toward higher quit rates among smokers with worse spirometry results.⁶

Recommendations

The US Preventive Services Task Force recommends against using spirometry to screen for chronic obstructive pulmonary disease, but advocates screening all adults for tobacco use and encouraging cessation.⁷

The authors of a Cochrane review found insufficient evidence to recommend using biomedical risk assessment (carbon monoxide blood levels, spirometry, genetic testing for alpha-1 antitrypsin deficiency) as a smoking cessation aid.⁸

Evidence summary

A prospective cohort study of 96 symptomatic women, average age 55.8 years, who were referred for coronary angiography, examined the accuracy of ETT compared with the gold standard of conventional coronary angiography.¹ Sensitivity, specificity, and diagnostic accuracy were comparatively low for ETT (TABLE). The authors concluded that ETT has limited diagnostic value in women with suspected CAD. Myocardial perfusion imaging (MPI) is more predictive of CAD, as a prospective cohort study of 68 symptomatic women demonstrated.²

TABLE
Suspect CAD in your female patient? Here’s how various tests compare with coronary angiography

A meta-analysis of 14 studies that compared dobutamine stress echocardiography with conventional coronary angiography in 901 women found an overall sensitivity of 72% and specificity of 88% for echocardiography.³

MDCT has high accuracy, but also some limitations
Three prospective cohort studies compared 64-, 40-, and 16-slice MDCT with conventional coronary angiography in 123, 21, and 70 symptomatic women, respectively, and each study demonstrated high sensitivity and specificity for MDCT in diagnosing CAD.^4-6 Diagnostic accuracy was similar among slice techniques. The studies had multiple limitations, including location (potential population bias), patient symptoms, and setting (potential referral bias).

All the studies of MDCT included symptomatic patients from cardiologists or tertiary care centers in Europe and Israel, potentially lessening the technique’s generalizability to many clinical settings. Moreover, the availability of MDCT is limited, especially compared with stress echocardiogram and MPI.

MDCT requires a heart rate <60 to 70 beats per minute, which necessitates giving beta-blockers to patients with higher heart rates; not all patients can tolerate the medication or lower heart rate. MDCT also requires giving intravenous contrast media to visualize the coronary arteries and exposes the patient to a high level of radiation.

Notably, all studies of ETT, MPI, stress echocardiography, and MDCT enrolled symptomatic patients, limiting their evaluation as screening tools.

Recommendations

The American Heart Association recommends testing symptomatic women with a Framing-ham risk score of 10% or greater. A 2005 consensus statement allows providers to rely on local practices and available tests, with the caveat that ETT is the preferred initial test.⁷

The American College of Radiology expert consensus panel recommends the use of stress nuclear imaging and chest radiography to evaluate patients with chronic chest pain and suspected CAD; the recommendation does not specify testing method based on sex.⁸

Evidence summary

A prospective cohort study of 96 symptomatic women, average age 55.8 years, who were referred for coronary angiography, examined the accuracy of ETT compared with the gold standard of conventional coronary angiography.¹ Sensitivity, specificity, and diagnostic accuracy were comparatively low for ETT (TABLE). The authors concluded that ETT has limited diagnostic value in women with suspected CAD. Myocardial perfusion imaging (MPI) is more predictive of CAD, as a prospective cohort study of 68 symptomatic women demonstrated.²

TABLE
Suspect CAD in your female patient? Here’s how various tests compare with coronary angiography

A meta-analysis of 14 studies that compared dobutamine stress echocardiography with conventional coronary angiography in 901 women found an overall sensitivity of 72% and specificity of 88% for echocardiography.³

MDCT has high accuracy, but also some limitations
Three prospective cohort studies compared 64-, 40-, and 16-slice MDCT with conventional coronary angiography in 123, 21, and 70 symptomatic women, respectively, and each study demonstrated high sensitivity and specificity for MDCT in diagnosing CAD.^4-6 Diagnostic accuracy was similar among slice techniques. The studies had multiple limitations, including location (potential population bias), patient symptoms, and setting (potential referral bias).

All the studies of MDCT included symptomatic patients from cardiologists or tertiary care centers in Europe and Israel, potentially lessening the technique’s generalizability to many clinical settings. Moreover, the availability of MDCT is limited, especially compared with stress echocardiogram and MPI.

MDCT requires a heart rate <60 to 70 beats per minute, which necessitates giving beta-blockers to patients with higher heart rates; not all patients can tolerate the medication or lower heart rate. MDCT also requires giving intravenous contrast media to visualize the coronary arteries and exposes the patient to a high level of radiation.

Notably, all studies of ETT, MPI, stress echocardiography, and MDCT enrolled symptomatic patients, limiting their evaluation as screening tools.

Recommendations

The American Heart Association recommends testing symptomatic women with a Framing-ham risk score of 10% or greater. A 2005 consensus statement allows providers to rely on local practices and available tests, with the caveat that ETT is the preferred initial test.⁷

The American College of Radiology expert consensus panel recommends the use of stress nuclear imaging and chest radiography to evaluate patients with chronic chest pain and suspected CAD; the recommendation does not specify testing method based on sex.⁸

Evidence summary

A prospective cohort study of 96 symptomatic women, average age 55.8 years, who were referred for coronary angiography, examined the accuracy of ETT compared with the gold standard of conventional coronary angiography.¹ Sensitivity, specificity, and diagnostic accuracy were comparatively low for ETT (TABLE). The authors concluded that ETT has limited diagnostic value in women with suspected CAD. Myocardial perfusion imaging (MPI) is more predictive of CAD, as a prospective cohort study of 68 symptomatic women demonstrated.²

TABLE
Suspect CAD in your female patient? Here’s how various tests compare with coronary angiography

A meta-analysis of 14 studies that compared dobutamine stress echocardiography with conventional coronary angiography in 901 women found an overall sensitivity of 72% and specificity of 88% for echocardiography.³

MDCT has high accuracy, but also some limitations
Three prospective cohort studies compared 64-, 40-, and 16-slice MDCT with conventional coronary angiography in 123, 21, and 70 symptomatic women, respectively, and each study demonstrated high sensitivity and specificity for MDCT in diagnosing CAD.^4-6 Diagnostic accuracy was similar among slice techniques. The studies had multiple limitations, including location (potential population bias), patient symptoms, and setting (potential referral bias).

All the studies of MDCT included symptomatic patients from cardiologists or tertiary care centers in Europe and Israel, potentially lessening the technique’s generalizability to many clinical settings. Moreover, the availability of MDCT is limited, especially compared with stress echocardiogram and MPI.

MDCT requires a heart rate <60 to 70 beats per minute, which necessitates giving beta-blockers to patients with higher heart rates; not all patients can tolerate the medication or lower heart rate. MDCT also requires giving intravenous contrast media to visualize the coronary arteries and exposes the patient to a high level of radiation.

Notably, all studies of ETT, MPI, stress echocardiography, and MDCT enrolled symptomatic patients, limiting their evaluation as screening tools.

Recommendations

The American Heart Association recommends testing symptomatic women with a Framing-ham risk score of 10% or greater. A 2005 consensus statement allows providers to rely on local practices and available tests, with the caveat that ETT is the preferred initial test.⁷

The American College of Radiology expert consensus panel recommends the use of stress nuclear imaging and chest radiography to evaluate patients with chronic chest pain and suspected CAD; the recommendation does not specify testing method based on sex.⁸

Evidence summary

A 2009 Cochrane review analyzed the results of 28 RCTs that evaluated the effect of exercise (aerobic, resistance, or mixed aerobic and resistance) compared with no exercise, pharmacotherapy, CBT, and light therapy on symptoms of depression as measured by several validated depression scales.¹ The authors of the review compared pooled data from several different psychometric scales by calculating the standard mean difference (SMD) and used the following “rule of thumb” when interpreting the data: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect.

Pooled analysis of 23 RCTs (N=907) comparing exercise with no exercise found that exercise significantly reduced symptoms of depression (SMD=-0.82; 95% confidence interval [CI], -1.12 to -0.51). However, significant heterogeneity between the studies limits these conclusions. Five RCTs (N= 218) showed a moderate effect of exercise on maintaining the antidepressant effect for 4 to 26 months after the intervention (SMD=-0.44; 95% CI, -0.71 to -0.18).

Subgroup analyses in the same review showed no significant difference between exercise and CBT (6 RCTs, N=152; SMD=-0.17; 95% CI, -0.51 to 0.18) or between exercise and antidepressant drugs in reducing depressive symptoms (2 RCTs, N=201; SMD=-0.04; 95% CI, -0.31 to 0.24). The small size of these studies limits the ability to detect a potentially important clinical difference. One small RCT (N=18) in the review showed that exercise reduced symptoms more effectively than light therapy (SMD=-6.4; 95% CI, -10.2 to -2.6).

Mixed exercise and more of it get better results
Subgroup analyses within the same Cochrane review showed that resistance exercise (SMD=-1.34; 95% CI, -2.07 to -0.61) and mixed exercise (SMD=-1.47; 95% CI, -2.56 to -0.37) reduced symptoms of depression more than aerobic exercise alone (SMD=-0.63; 95% CI, -0.95 to -0.30). A very small RCT (N=23) noted larger reductions in Beck Depression Inventory scores among patients who exercised 3 to 5 times a week—30-minute sessions at 60% to 80% maximum heart rate—compared with patients who exercised only once a week (mean difference=-10.46; 95% CI, -16.06 to -4.85).²

Meditative exercise shows positive effect
A systematic review in 2008 assessed 6 RCTs that evaluated meditative exercises such as yoga, tai chi, and qigong for treating depression. All 6 studies showed a “positive response” to treatment, with 5 studies reporting a statistically significant reduction in depression scores. Because a great deal of heterogeneity existed among study parameters, no quantitative analysis was done to estimate the size of the positive effect.³

Recommendations

The National Institute for Health and Clinical Excellence recommends structured, supervised exercise programs, 3 times a week for 45 to 60 minutes each session over 10 to 14 weeks to treat mild depression.⁴

The Institute for Clinical Systems Improvement guideline recommends physical activity for 30 minutes 3 to 5 days a week to decrease symptoms of major depression.⁵

Evidence summary

A 2009 Cochrane review analyzed the results of 28 RCTs that evaluated the effect of exercise (aerobic, resistance, or mixed aerobic and resistance) compared with no exercise, pharmacotherapy, CBT, and light therapy on symptoms of depression as measured by several validated depression scales.¹ The authors of the review compared pooled data from several different psychometric scales by calculating the standard mean difference (SMD) and used the following “rule of thumb” when interpreting the data: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect.

Pooled analysis of 23 RCTs (N=907) comparing exercise with no exercise found that exercise significantly reduced symptoms of depression (SMD=-0.82; 95% confidence interval [CI], -1.12 to -0.51). However, significant heterogeneity between the studies limits these conclusions. Five RCTs (N= 218) showed a moderate effect of exercise on maintaining the antidepressant effect for 4 to 26 months after the intervention (SMD=-0.44; 95% CI, -0.71 to -0.18).

Subgroup analyses in the same review showed no significant difference between exercise and CBT (6 RCTs, N=152; SMD=-0.17; 95% CI, -0.51 to 0.18) or between exercise and antidepressant drugs in reducing depressive symptoms (2 RCTs, N=201; SMD=-0.04; 95% CI, -0.31 to 0.24). The small size of these studies limits the ability to detect a potentially important clinical difference. One small RCT (N=18) in the review showed that exercise reduced symptoms more effectively than light therapy (SMD=-6.4; 95% CI, -10.2 to -2.6).

Mixed exercise and more of it get better results
Subgroup analyses within the same Cochrane review showed that resistance exercise (SMD=-1.34; 95% CI, -2.07 to -0.61) and mixed exercise (SMD=-1.47; 95% CI, -2.56 to -0.37) reduced symptoms of depression more than aerobic exercise alone (SMD=-0.63; 95% CI, -0.95 to -0.30). A very small RCT (N=23) noted larger reductions in Beck Depression Inventory scores among patients who exercised 3 to 5 times a week—30-minute sessions at 60% to 80% maximum heart rate—compared with patients who exercised only once a week (mean difference=-10.46; 95% CI, -16.06 to -4.85).²

Meditative exercise shows positive effect
A systematic review in 2008 assessed 6 RCTs that evaluated meditative exercises such as yoga, tai chi, and qigong for treating depression. All 6 studies showed a “positive response” to treatment, with 5 studies reporting a statistically significant reduction in depression scores. Because a great deal of heterogeneity existed among study parameters, no quantitative analysis was done to estimate the size of the positive effect.³

Recommendations

The National Institute for Health and Clinical Excellence recommends structured, supervised exercise programs, 3 times a week for 45 to 60 minutes each session over 10 to 14 weeks to treat mild depression.⁴

The Institute for Clinical Systems Improvement guideline recommends physical activity for 30 minutes 3 to 5 days a week to decrease symptoms of major depression.⁵

Evidence summary

A 2009 Cochrane review analyzed the results of 28 RCTs that evaluated the effect of exercise (aerobic, resistance, or mixed aerobic and resistance) compared with no exercise, pharmacotherapy, CBT, and light therapy on symptoms of depression as measured by several validated depression scales.¹ The authors of the review compared pooled data from several different psychometric scales by calculating the standard mean difference (SMD) and used the following “rule of thumb” when interpreting the data: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect.

Pooled analysis of 23 RCTs (N=907) comparing exercise with no exercise found that exercise significantly reduced symptoms of depression (SMD=-0.82; 95% confidence interval [CI], -1.12 to -0.51). However, significant heterogeneity between the studies limits these conclusions. Five RCTs (N= 218) showed a moderate effect of exercise on maintaining the antidepressant effect for 4 to 26 months after the intervention (SMD=-0.44; 95% CI, -0.71 to -0.18).

Subgroup analyses in the same review showed no significant difference between exercise and CBT (6 RCTs, N=152; SMD=-0.17; 95% CI, -0.51 to 0.18) or between exercise and antidepressant drugs in reducing depressive symptoms (2 RCTs, N=201; SMD=-0.04; 95% CI, -0.31 to 0.24). The small size of these studies limits the ability to detect a potentially important clinical difference. One small RCT (N=18) in the review showed that exercise reduced symptoms more effectively than light therapy (SMD=-6.4; 95% CI, -10.2 to -2.6).

Mixed exercise and more of it get better results
Subgroup analyses within the same Cochrane review showed that resistance exercise (SMD=-1.34; 95% CI, -2.07 to -0.61) and mixed exercise (SMD=-1.47; 95% CI, -2.56 to -0.37) reduced symptoms of depression more than aerobic exercise alone (SMD=-0.63; 95% CI, -0.95 to -0.30). A very small RCT (N=23) noted larger reductions in Beck Depression Inventory scores among patients who exercised 3 to 5 times a week—30-minute sessions at 60% to 80% maximum heart rate—compared with patients who exercised only once a week (mean difference=-10.46; 95% CI, -16.06 to -4.85).²

Meditative exercise shows positive effect
A systematic review in 2008 assessed 6 RCTs that evaluated meditative exercises such as yoga, tai chi, and qigong for treating depression. All 6 studies showed a “positive response” to treatment, with 5 studies reporting a statistically significant reduction in depression scores. Because a great deal of heterogeneity existed among study parameters, no quantitative analysis was done to estimate the size of the positive effect.³

Recommendations

The National Institute for Health and Clinical Excellence recommends structured, supervised exercise programs, 3 times a week for 45 to 60 minutes each session over 10 to 14 weeks to treat mild depression.⁴

The Institute for Clinical Systems Improvement guideline recommends physical activity for 30 minutes 3 to 5 days a week to decrease symptoms of major depression.⁵

Evidence summary

The American Academy of Allergy, Asthma and Immunology (AAAAI) states that a double-blind, placebo-controlled OFC is the best test for diagnosing infants clinically suspected of having food allergies (that is, who develop gastrointestinal symptoms after eating a specific food). However, performing an OFC in an infant is often difficult and potentially dangerous, especially if a severe allergy is suspected; testing also may eliminate nutritious foods, such as milk and eggs, from the infant’s diet.¹ For these reasons, physicians have sought simpler alternatives to the OFC.

Comparisons of serum and skin testing with OFCs produce variable, weak results
Two large cohort studies compared OFCs with serum and skin testing in infants, children, and teenagers. Overall, serum and skin testing didn’t produce robust results and the results varied with the antigen (TABLE).

TABLE
How allergy tests in infants and children compare with an oral food challenge

In 1 study, researchers compared specific serum IgE levels with OFC results for 4 foods—milk, eggs, wheat, and soy—in 501 consecutive pediatric patients referred to an allergy ward based on clinical or parental suspicion of food allergy. Children ranged in age from 1 month to 16 years (median age 13 months); results for infants were not provided separately. Eighty-eight percent of the children were atopic. Investigators measured serum IgE (using the Pharmacia CAP-system fluorescence enzyme immunoassay) before administering the OFCs.

Of 992 OFCs performed, 445 (45%) were positive (defined as producing urticaria, angioedema, wheezing, vomiting, diarrhea, abdominal pain, shock, or exacerbation of eczema). Most OFCs (73%) were double-blind placebo-controlled, but investigators performed open OFCs in infants and in children with a history of immediate allergic reactions. Investigators retrospectively analyzed serum-specific IgE levels for the 4 food antigens and compared them with the results of the OFCs. Positive likelihood ratios (LR+) for IgE testing ranged from 1.3 to 2.0 for the 4 antigens; negative likelihood ratios (LR–) ranged from 0.31 to 0.59.²

The second cohort study compared APT and SPT with OFCs for the same 4 food antigens (milk, eggs, wheat, soy) in 437 children. The study population comprised consecutive referrals to a pediatric immunology department based on either parental suspicion of a food allergy or a positive IgE test. The children ranged in age from 3 months to 14 years (median age 13 months); results for infants weren’t provided separately. Ninety percent of the children were atopic. Investigators performed APTs and SPTs for the 4 food antigens on all children and OFCs only for foods that were clinically suspect (total OFCs=873).

As in the previous study, investigators performed open OFCs (23%) in infants and children with a history of immediate reaction. A positive APT was defined by erythema with infiltration or papules, and a positive SPT by a wheal ≥3 mm. For the SPT, the LR+ ranged from 1.9 to 2.8 for the 4 antigens, and the LR–ranged from 0.13 (for egg) to 0.84. For the APT, the LR+ ranged from 1.6 to 6.2 (for milk), whereas the LR– was of little value, ranging from 0.68 to 0.90.³

For milk and eggs, the larger the wheal, the more sensitive the skin test
The size of the wheal may increase the sensitivity of the SPT in some situations. A cohort study similar to the ones described previously compared SPT with OFCs in children with possible food allergies and found that a large SPT wheal was highly correlated with OFC-confirmed allergy to milk and eggs.⁴

Investigators recruited 385 children—3 months to 14 years of age (median age 22 months), results for infants not provided separately—from consecutive referrals to a pediatric immunology department. Most children (87%) were atopic. Investigators performed SPTs, followed by OFCs for milk, egg, wheat, and soy allergens. Overall, 312 (43%) of the OFCs were positive. Wheals measuring ≥13 mm for eggs and ≥12.5 mm for milk correlated well with OFC results (95% positive predictive value). Wheal sizes for wheat and soy were poorly predictive, however.⁴

No validation yet for new techniques to improve accuracy and safety
New techniques to improve the accuracy and safety of allergy testing have yet to be validated clinically. One cohort study of 58 children that used fresh fruit or vegetable preparations for SPT instead of commonly used commercial extracts found added sensitivity.⁵ Another cohort study of 142 children allowed suspect foods to contact only the labial mucosa in order to reduce the risk of systemic reactions (1 case of anaphylaxis occurred nevertheless).⁶

Recommendations

The AAAAI guidelines state that history and physical examination help determine that food is causing symptoms and that an OFC is diagnostic of food allergy (but risks and benefits must be considered, including the possibility of severe adverse reaction).¹ The guidelines note that other available tests, including food-specific IgE and skin tests, are not specific enough for screening but may be used when a particular food allergy is clinically suspected.

Evidence summary

The American Academy of Allergy, Asthma and Immunology (AAAAI) states that a double-blind, placebo-controlled OFC is the best test for diagnosing infants clinically suspected of having food allergies (that is, who develop gastrointestinal symptoms after eating a specific food). However, performing an OFC in an infant is often difficult and potentially dangerous, especially if a severe allergy is suspected; testing also may eliminate nutritious foods, such as milk and eggs, from the infant’s diet.¹ For these reasons, physicians have sought simpler alternatives to the OFC.

Comparisons of serum and skin testing with OFCs produce variable, weak results
Two large cohort studies compared OFCs with serum and skin testing in infants, children, and teenagers. Overall, serum and skin testing didn’t produce robust results and the results varied with the antigen (TABLE).

TABLE
How allergy tests in infants and children compare with an oral food challenge

In 1 study, researchers compared specific serum IgE levels with OFC results for 4 foods—milk, eggs, wheat, and soy—in 501 consecutive pediatric patients referred to an allergy ward based on clinical or parental suspicion of food allergy. Children ranged in age from 1 month to 16 years (median age 13 months); results for infants were not provided separately. Eighty-eight percent of the children were atopic. Investigators measured serum IgE (using the Pharmacia CAP-system fluorescence enzyme immunoassay) before administering the OFCs.

Of 992 OFCs performed, 445 (45%) were positive (defined as producing urticaria, angioedema, wheezing, vomiting, diarrhea, abdominal pain, shock, or exacerbation of eczema). Most OFCs (73%) were double-blind placebo-controlled, but investigators performed open OFCs in infants and in children with a history of immediate allergic reactions. Investigators retrospectively analyzed serum-specific IgE levels for the 4 food antigens and compared them with the results of the OFCs. Positive likelihood ratios (LR+) for IgE testing ranged from 1.3 to 2.0 for the 4 antigens; negative likelihood ratios (LR–) ranged from 0.31 to 0.59.²

The second cohort study compared APT and SPT with OFCs for the same 4 food antigens (milk, eggs, wheat, soy) in 437 children. The study population comprised consecutive referrals to a pediatric immunology department based on either parental suspicion of a food allergy or a positive IgE test. The children ranged in age from 3 months to 14 years (median age 13 months); results for infants weren’t provided separately. Ninety percent of the children were atopic. Investigators performed APTs and SPTs for the 4 food antigens on all children and OFCs only for foods that were clinically suspect (total OFCs=873).

As in the previous study, investigators performed open OFCs (23%) in infants and children with a history of immediate reaction. A positive APT was defined by erythema with infiltration or papules, and a positive SPT by a wheal ≥3 mm. For the SPT, the LR+ ranged from 1.9 to 2.8 for the 4 antigens, and the LR–ranged from 0.13 (for egg) to 0.84. For the APT, the LR+ ranged from 1.6 to 6.2 (for milk), whereas the LR– was of little value, ranging from 0.68 to 0.90.³

For milk and eggs, the larger the wheal, the more sensitive the skin test
The size of the wheal may increase the sensitivity of the SPT in some situations. A cohort study similar to the ones described previously compared SPT with OFCs in children with possible food allergies and found that a large SPT wheal was highly correlated with OFC-confirmed allergy to milk and eggs.⁴

Investigators recruited 385 children—3 months to 14 years of age (median age 22 months), results for infants not provided separately—from consecutive referrals to a pediatric immunology department. Most children (87%) were atopic. Investigators performed SPTs, followed by OFCs for milk, egg, wheat, and soy allergens. Overall, 312 (43%) of the OFCs were positive. Wheals measuring ≥13 mm for eggs and ≥12.5 mm for milk correlated well with OFC results (95% positive predictive value). Wheal sizes for wheat and soy were poorly predictive, however.⁴

No validation yet for new techniques to improve accuracy and safety
New techniques to improve the accuracy and safety of allergy testing have yet to be validated clinically. One cohort study of 58 children that used fresh fruit or vegetable preparations for SPT instead of commonly used commercial extracts found added sensitivity.⁵ Another cohort study of 142 children allowed suspect foods to contact only the labial mucosa in order to reduce the risk of systemic reactions (1 case of anaphylaxis occurred nevertheless).⁶

Recommendations

The AAAAI guidelines state that history and physical examination help determine that food is causing symptoms and that an OFC is diagnostic of food allergy (but risks and benefits must be considered, including the possibility of severe adverse reaction).¹ The guidelines note that other available tests, including food-specific IgE and skin tests, are not specific enough for screening but may be used when a particular food allergy is clinically suspected.

Evidence summary

The American Academy of Allergy, Asthma and Immunology (AAAAI) states that a double-blind, placebo-controlled OFC is the best test for diagnosing infants clinically suspected of having food allergies (that is, who develop gastrointestinal symptoms after eating a specific food). However, performing an OFC in an infant is often difficult and potentially dangerous, especially if a severe allergy is suspected; testing also may eliminate nutritious foods, such as milk and eggs, from the infant’s diet.¹ For these reasons, physicians have sought simpler alternatives to the OFC.

Comparisons of serum and skin testing with OFCs produce variable, weak results
Two large cohort studies compared OFCs with serum and skin testing in infants, children, and teenagers. Overall, serum and skin testing didn’t produce robust results and the results varied with the antigen (TABLE).

TABLE
How allergy tests in infants and children compare with an oral food challenge

In 1 study, researchers compared specific serum IgE levels with OFC results for 4 foods—milk, eggs, wheat, and soy—in 501 consecutive pediatric patients referred to an allergy ward based on clinical or parental suspicion of food allergy. Children ranged in age from 1 month to 16 years (median age 13 months); results for infants were not provided separately. Eighty-eight percent of the children were atopic. Investigators measured serum IgE (using the Pharmacia CAP-system fluorescence enzyme immunoassay) before administering the OFCs.

Of 992 OFCs performed, 445 (45%) were positive (defined as producing urticaria, angioedema, wheezing, vomiting, diarrhea, abdominal pain, shock, or exacerbation of eczema). Most OFCs (73%) were double-blind placebo-controlled, but investigators performed open OFCs in infants and in children with a history of immediate allergic reactions. Investigators retrospectively analyzed serum-specific IgE levels for the 4 food antigens and compared them with the results of the OFCs. Positive likelihood ratios (LR+) for IgE testing ranged from 1.3 to 2.0 for the 4 antigens; negative likelihood ratios (LR–) ranged from 0.31 to 0.59.²

The second cohort study compared APT and SPT with OFCs for the same 4 food antigens (milk, eggs, wheat, soy) in 437 children. The study population comprised consecutive referrals to a pediatric immunology department based on either parental suspicion of a food allergy or a positive IgE test. The children ranged in age from 3 months to 14 years (median age 13 months); results for infants weren’t provided separately. Ninety percent of the children were atopic. Investigators performed APTs and SPTs for the 4 food antigens on all children and OFCs only for foods that were clinically suspect (total OFCs=873).

As in the previous study, investigators performed open OFCs (23%) in infants and children with a history of immediate reaction. A positive APT was defined by erythema with infiltration or papules, and a positive SPT by a wheal ≥3 mm. For the SPT, the LR+ ranged from 1.9 to 2.8 for the 4 antigens, and the LR–ranged from 0.13 (for egg) to 0.84. For the APT, the LR+ ranged from 1.6 to 6.2 (for milk), whereas the LR– was of little value, ranging from 0.68 to 0.90.³

For milk and eggs, the larger the wheal, the more sensitive the skin test
The size of the wheal may increase the sensitivity of the SPT in some situations. A cohort study similar to the ones described previously compared SPT with OFCs in children with possible food allergies and found that a large SPT wheal was highly correlated with OFC-confirmed allergy to milk and eggs.⁴

Investigators recruited 385 children—3 months to 14 years of age (median age 22 months), results for infants not provided separately—from consecutive referrals to a pediatric immunology department. Most children (87%) were atopic. Investigators performed SPTs, followed by OFCs for milk, egg, wheat, and soy allergens. Overall, 312 (43%) of the OFCs were positive. Wheals measuring ≥13 mm for eggs and ≥12.5 mm for milk correlated well with OFC results (95% positive predictive value). Wheal sizes for wheat and soy were poorly predictive, however.⁴

No validation yet for new techniques to improve accuracy and safety
New techniques to improve the accuracy and safety of allergy testing have yet to be validated clinically. One cohort study of 58 children that used fresh fruit or vegetable preparations for SPT instead of commonly used commercial extracts found added sensitivity.⁵ Another cohort study of 142 children allowed suspect foods to contact only the labial mucosa in order to reduce the risk of systemic reactions (1 case of anaphylaxis occurred nevertheless).⁶

Recommendations

The AAAAI guidelines state that history and physical examination help determine that food is causing symptoms and that an OFC is diagnostic of food allergy (but risks and benefits must be considered, including the possibility of severe adverse reaction).¹ The guidelines note that other available tests, including food-specific IgE and skin tests, are not specific enough for screening but may be used when a particular food allergy is clinically suspected.

Evidence summary

A 2-part meta-analysis of 26 studies enrolling men, women, or both, showed a significant inverse association between red wine consumption and fatal and nonfatal cardiovascular events. The first part, encompassing 13 studies (5 prospective cohort and 8 case-control studies with a total of 209,418 participants), compared moderate wine drinkers with non-drinkers and heavy or binge drinkers. Moderate drinkers consumed an average of 1 to 2 drinks per day.¹ This meta-analysis, and other studies described in this summary, defined a drink as 130 mL of wine with 12% ethanol content.

For all 13 studies combined, moderate wine drinking significantly reduced cardiovascular events at 2 to 24 years of follow-up compared with no drinking and heavy drinking (relative risk [RR]=0.68; 95% confidence interval [CI], 0.59-0.77). A pool of the 7 studies that enrolled both male and female participants also found that wine drinking significantly reduced cardiovascular events (RR=0.53; 95% CI, 0.42-0.68). However, pooled results from the 6 studies with exclusively male participants found no difference in cardiovascular events with wine consumption (RR=0.87; 95% CI, 0.68-1.12). Beer drinking, which was also evaluated, produced statistically significant risk reductions in studies of both men and women; the effect was smaller in men-only studies.¹

CV risk decreases with increased wine intake—to a point
The second part of the meta-analysis, 7 prospective cohort and 3 case-control studies with a total of 176,042 participants, found an apparent J-shaped dose-response relationship between wine intake and cardiovascular risk reduction. Daily consumption ranged from 0 to 1738 mL, although most participants had 0 to 3 drinks (390 mL) per day. Data from the 7 prospective studies illustrated a progressive decrease in cardiovascular risk as wine intake increased to 150 mL per day. Consuming larger amounts of wine (as much as 750 mL per day) showed a trend toward further cardiovascular risk reduction, but the trend wasn’t statistically significant.¹

High flavonoid intake is associated with lower CHD mortality

A meta-analysis of 7 prospective cohort studies including 105,000 men and women 30 to 84 years of age indicated that a high dietary intake of flavonoids (present in larger amounts in red wine, chocolate, tea, and other foods) correlated with reduced CHD mortality. Participants whose flavonoid consumption was in the highest third had significantly less CHD mortality than participants in the bottom third (RR=0.80; 95% CI, 0.69-0.93; P<.001). The meta-analysis couldn’t determine whether the flavonoid content of red wine confers additional cardiovascular benefit beyond that of alcohol alone.²

Heavy drinking increases risk of stroke
A meta-analysis of 41 studies (3 cross-sectional, 21 case-control, and 17 cohort studies) enrolling both men and women, correlated heavy alcohol drinking (>4 drinks per day, on average) with increased risk of stroke. Seven of 9 retrospective studies associated heavy drinking with an increase in risk as great as 6.5-fold for hemorrhagic and ischemic stroke, but found no consistent association between stroke and light-to-moderate drinking. Evidence was insufficient to evaluate stroke risks specific to low or moderate wine intake.³

Recommendations

The US Department of Health and Human Services’ Dietary Guidelines for Americans 2005 state that moderate daily wine intake in adults (5 oz for women and 10 oz for men) is associated with the lowest all-cause mortality and CHD. The guidelines warn against drinking by people who are susceptible to the harmful effects of alcohol and participants in activities that require attention, skill, or coordination.⁴

The American Heart Association states that moderate alcohol consumption (1-2 drinks daily) may be considered safe in the absence of contraindications, and recommends consulting a physician first.⁵

The National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health says that moderate drinkers are less likely to die from coronary artery disease than are people who don’t drink any alcohol or who drink more alcohol. It recommends against nondrinkers starting to drink solely to benefit their hearts, however.⁶

Evidence summary

A 2-part meta-analysis of 26 studies enrolling men, women, or both, showed a significant inverse association between red wine consumption and fatal and nonfatal cardiovascular events. The first part, encompassing 13 studies (5 prospective cohort and 8 case-control studies with a total of 209,418 participants), compared moderate wine drinkers with non-drinkers and heavy or binge drinkers. Moderate drinkers consumed an average of 1 to 2 drinks per day.¹ This meta-analysis, and other studies described in this summary, defined a drink as 130 mL of wine with 12% ethanol content.

For all 13 studies combined, moderate wine drinking significantly reduced cardiovascular events at 2 to 24 years of follow-up compared with no drinking and heavy drinking (relative risk [RR]=0.68; 95% confidence interval [CI], 0.59-0.77). A pool of the 7 studies that enrolled both male and female participants also found that wine drinking significantly reduced cardiovascular events (RR=0.53; 95% CI, 0.42-0.68). However, pooled results from the 6 studies with exclusively male participants found no difference in cardiovascular events with wine consumption (RR=0.87; 95% CI, 0.68-1.12). Beer drinking, which was also evaluated, produced statistically significant risk reductions in studies of both men and women; the effect was smaller in men-only studies.¹

CV risk decreases with increased wine intake—to a point
The second part of the meta-analysis, 7 prospective cohort and 3 case-control studies with a total of 176,042 participants, found an apparent J-shaped dose-response relationship between wine intake and cardiovascular risk reduction. Daily consumption ranged from 0 to 1738 mL, although most participants had 0 to 3 drinks (390 mL) per day. Data from the 7 prospective studies illustrated a progressive decrease in cardiovascular risk as wine intake increased to 150 mL per day. Consuming larger amounts of wine (as much as 750 mL per day) showed a trend toward further cardiovascular risk reduction, but the trend wasn’t statistically significant.¹

High flavonoid intake is associated with lower CHD mortality

A meta-analysis of 7 prospective cohort studies including 105,000 men and women 30 to 84 years of age indicated that a high dietary intake of flavonoids (present in larger amounts in red wine, chocolate, tea, and other foods) correlated with reduced CHD mortality. Participants whose flavonoid consumption was in the highest third had significantly less CHD mortality than participants in the bottom third (RR=0.80; 95% CI, 0.69-0.93; P<.001). The meta-analysis couldn’t determine whether the flavonoid content of red wine confers additional cardiovascular benefit beyond that of alcohol alone.²

Heavy drinking increases risk of stroke
A meta-analysis of 41 studies (3 cross-sectional, 21 case-control, and 17 cohort studies) enrolling both men and women, correlated heavy alcohol drinking (>4 drinks per day, on average) with increased risk of stroke. Seven of 9 retrospective studies associated heavy drinking with an increase in risk as great as 6.5-fold for hemorrhagic and ischemic stroke, but found no consistent association between stroke and light-to-moderate drinking. Evidence was insufficient to evaluate stroke risks specific to low or moderate wine intake.³

Recommendations

The US Department of Health and Human Services’ Dietary Guidelines for Americans 2005 state that moderate daily wine intake in adults (5 oz for women and 10 oz for men) is associated with the lowest all-cause mortality and CHD. The guidelines warn against drinking by people who are susceptible to the harmful effects of alcohol and participants in activities that require attention, skill, or coordination.⁴

The American Heart Association states that moderate alcohol consumption (1-2 drinks daily) may be considered safe in the absence of contraindications, and recommends consulting a physician first.⁵

The National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health says that moderate drinkers are less likely to die from coronary artery disease than are people who don’t drink any alcohol or who drink more alcohol. It recommends against nondrinkers starting to drink solely to benefit their hearts, however.⁶

Evidence summary

A 2-part meta-analysis of 26 studies enrolling men, women, or both, showed a significant inverse association between red wine consumption and fatal and nonfatal cardiovascular events. The first part, encompassing 13 studies (5 prospective cohort and 8 case-control studies with a total of 209,418 participants), compared moderate wine drinkers with non-drinkers and heavy or binge drinkers. Moderate drinkers consumed an average of 1 to 2 drinks per day.¹ This meta-analysis, and other studies described in this summary, defined a drink as 130 mL of wine with 12% ethanol content.

For all 13 studies combined, moderate wine drinking significantly reduced cardiovascular events at 2 to 24 years of follow-up compared with no drinking and heavy drinking (relative risk [RR]=0.68; 95% confidence interval [CI], 0.59-0.77). A pool of the 7 studies that enrolled both male and female participants also found that wine drinking significantly reduced cardiovascular events (RR=0.53; 95% CI, 0.42-0.68). However, pooled results from the 6 studies with exclusively male participants found no difference in cardiovascular events with wine consumption (RR=0.87; 95% CI, 0.68-1.12). Beer drinking, which was also evaluated, produced statistically significant risk reductions in studies of both men and women; the effect was smaller in men-only studies.¹

CV risk decreases with increased wine intake—to a point
The second part of the meta-analysis, 7 prospective cohort and 3 case-control studies with a total of 176,042 participants, found an apparent J-shaped dose-response relationship between wine intake and cardiovascular risk reduction. Daily consumption ranged from 0 to 1738 mL, although most participants had 0 to 3 drinks (390 mL) per day. Data from the 7 prospective studies illustrated a progressive decrease in cardiovascular risk as wine intake increased to 150 mL per day. Consuming larger amounts of wine (as much as 750 mL per day) showed a trend toward further cardiovascular risk reduction, but the trend wasn’t statistically significant.¹

High flavonoid intake is associated with lower CHD mortality

A meta-analysis of 7 prospective cohort studies including 105,000 men and women 30 to 84 years of age indicated that a high dietary intake of flavonoids (present in larger amounts in red wine, chocolate, tea, and other foods) correlated with reduced CHD mortality. Participants whose flavonoid consumption was in the highest third had significantly less CHD mortality than participants in the bottom third (RR=0.80; 95% CI, 0.69-0.93; P<.001). The meta-analysis couldn’t determine whether the flavonoid content of red wine confers additional cardiovascular benefit beyond that of alcohol alone.²

Heavy drinking increases risk of stroke
A meta-analysis of 41 studies (3 cross-sectional, 21 case-control, and 17 cohort studies) enrolling both men and women, correlated heavy alcohol drinking (>4 drinks per day, on average) with increased risk of stroke. Seven of 9 retrospective studies associated heavy drinking with an increase in risk as great as 6.5-fold for hemorrhagic and ischemic stroke, but found no consistent association between stroke and light-to-moderate drinking. Evidence was insufficient to evaluate stroke risks specific to low or moderate wine intake.³

Recommendations

The US Department of Health and Human Services’ Dietary Guidelines for Americans 2005 state that moderate daily wine intake in adults (5 oz for women and 10 oz for men) is associated with the lowest all-cause mortality and CHD. The guidelines warn against drinking by people who are susceptible to the harmful effects of alcohol and participants in activities that require attention, skill, or coordination.⁴

The American Heart Association states that moderate alcohol consumption (1-2 drinks daily) may be considered safe in the absence of contraindications, and recommends consulting a physician first.⁵

The National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health says that moderate drinkers are less likely to die from coronary artery disease than are people who don’t drink any alcohol or who drink more alcohol. It recommends against nondrinkers starting to drink solely to benefit their hearts, however.⁶

Evidence Summary

One RCT examined PE rates in 400 patients with acute proximal DVT who were randomized to receive or not receive a permanent IVCF and also randomized to receive either unfractionated heparin or low-molecular-weight heparin for at least the first 3 months.^1,2 Patients with a contraindication to anticoagulation or history of anticoagulation failure were excluded.

After 8 years of follow-up, symptomatic PE occurred less often in the filter group than the nonfilter group (6.2% vs 15.1%; P=.008; hazard ratio [HR]=0.36, 95% confidence interval [CI], 0.17-0.77; number needed to treat [NNT]=11.2). The filter group had a higher incidence of recurrent DVT than the nonfilter group (35.7% vs 27.5%; HR=1.52, 95% CI, 1.02- 2.27; number needed to harm=12.2).^1,2

The study lacked statistical power to draw any conclusion about the efficacy of IVCFs in preventing PE over shorter time periods or in reducing PE-related or overall mortality.³ Further research, including RCTs, needs to be done to determine how the efficacy of endovascular filters compares with standard PE prophylaxis.

How often does PE occur in patients with filters?
Patients with DVT generally have associated PE 10% of the time.⁴ Several cohort studies have examined the prevalence of recurrent PE in pa- tients with IVCFs, but none compared preva- lence in patients with and without filters.

A prospective cohort study followed 481 patients who received an IVCF because of ei- ther a contraindication to anticoagulation or sustained recurrent embolization despite ad- equate anticoagulation. Of the patients who had a filter for 6 months or longer, 2% had clinically suspected PE, but PE was confirmed in only 0.5%.⁵

Another multicenter, prospective cohort study (N=222) found radiographically con- firmed PE after filter placement in only 2% of patients with IVCFs after a mean follow-up of 15 months.⁶

A retrospective cohort study (N=318) concluded that 3.1% of the patients with IVCFs had a recurrent PE, diagnosed radiographically.⁷

A single-center retrospective cohort study of 1731 patients with IVCFs placed for various indications showed PE in 5.6% of patients. Some embolisms were clinically suspected and not confirmed.⁸

Complications of filter placement
Complications from IVCF placement generally occur less than 3% of the time. The most common complication is postthrombotic syndrome (70%). Risks associated with IVCF placement include DVT, postthrombotic syndrome, maldeployed filter, caval thrombosis, retroperitoneal hemorrhage, malposition, filter migration, arrhythmia, insertion site complications (such as infection or hematoma), PE, myocardial infarction, and death.^1,2,5-12

Recommendations

The American College of Chest Physicians recommends considering an IVCF for patients with DVT who have a contraindication to anticoagulation, complication of anticoagulation, or recurrent thromboembolism despite adequate anticoagulation.¹²

Evidence Summary

One RCT examined PE rates in 400 patients with acute proximal DVT who were randomized to receive or not receive a permanent IVCF and also randomized to receive either unfractionated heparin or low-molecular-weight heparin for at least the first 3 months.^1,2 Patients with a contraindication to anticoagulation or history of anticoagulation failure were excluded.

After 8 years of follow-up, symptomatic PE occurred less often in the filter group than the nonfilter group (6.2% vs 15.1%; P=.008; hazard ratio [HR]=0.36, 95% confidence interval [CI], 0.17-0.77; number needed to treat [NNT]=11.2). The filter group had a higher incidence of recurrent DVT than the nonfilter group (35.7% vs 27.5%; HR=1.52, 95% CI, 1.02- 2.27; number needed to harm=12.2).^1,2

The study lacked statistical power to draw any conclusion about the efficacy of IVCFs in preventing PE over shorter time periods or in reducing PE-related or overall mortality.³ Further research, including RCTs, needs to be done to determine how the efficacy of endovascular filters compares with standard PE prophylaxis.

How often does PE occur in patients with filters?
Patients with DVT generally have associated PE 10% of the time.⁴ Several cohort studies have examined the prevalence of recurrent PE in pa- tients with IVCFs, but none compared preva- lence in patients with and without filters.

A prospective cohort study followed 481 patients who received an IVCF because of ei- ther a contraindication to anticoagulation or sustained recurrent embolization despite ad- equate anticoagulation. Of the patients who had a filter for 6 months or longer, 2% had clinically suspected PE, but PE was confirmed in only 0.5%.⁵

Another multicenter, prospective cohort study (N=222) found radiographically con- firmed PE after filter placement in only 2% of patients with IVCFs after a mean follow-up of 15 months.⁶

A retrospective cohort study (N=318) concluded that 3.1% of the patients with IVCFs had a recurrent PE, diagnosed radiographically.⁷

A single-center retrospective cohort study of 1731 patients with IVCFs placed for various indications showed PE in 5.6% of patients. Some embolisms were clinically suspected and not confirmed.⁸

Complications of filter placement
Complications from IVCF placement generally occur less than 3% of the time. The most common complication is postthrombotic syndrome (70%). Risks associated with IVCF placement include DVT, postthrombotic syndrome, maldeployed filter, caval thrombosis, retroperitoneal hemorrhage, malposition, filter migration, arrhythmia, insertion site complications (such as infection or hematoma), PE, myocardial infarction, and death.^1,2,5-12

Recommendations

The American College of Chest Physicians recommends considering an IVCF for patients with DVT who have a contraindication to anticoagulation, complication of anticoagulation, or recurrent thromboembolism despite adequate anticoagulation.¹²

Evidence Summary

One RCT examined PE rates in 400 patients with acute proximal DVT who were randomized to receive or not receive a permanent IVCF and also randomized to receive either unfractionated heparin or low-molecular-weight heparin for at least the first 3 months.^1,2 Patients with a contraindication to anticoagulation or history of anticoagulation failure were excluded.

After 8 years of follow-up, symptomatic PE occurred less often in the filter group than the nonfilter group (6.2% vs 15.1%; P=.008; hazard ratio [HR]=0.36, 95% confidence interval [CI], 0.17-0.77; number needed to treat [NNT]=11.2). The filter group had a higher incidence of recurrent DVT than the nonfilter group (35.7% vs 27.5%; HR=1.52, 95% CI, 1.02- 2.27; number needed to harm=12.2).^1,2

The study lacked statistical power to draw any conclusion about the efficacy of IVCFs in preventing PE over shorter time periods or in reducing PE-related or overall mortality.³ Further research, including RCTs, needs to be done to determine how the efficacy of endovascular filters compares with standard PE prophylaxis.

How often does PE occur in patients with filters?
Patients with DVT generally have associated PE 10% of the time.⁴ Several cohort studies have examined the prevalence of recurrent PE in pa- tients with IVCFs, but none compared preva- lence in patients with and without filters.

A prospective cohort study followed 481 patients who received an IVCF because of ei- ther a contraindication to anticoagulation or sustained recurrent embolization despite ad- equate anticoagulation. Of the patients who had a filter for 6 months or longer, 2% had clinically suspected PE, but PE was confirmed in only 0.5%.⁵

Another multicenter, prospective cohort study (N=222) found radiographically con- firmed PE after filter placement in only 2% of patients with IVCFs after a mean follow-up of 15 months.⁶

A retrospective cohort study (N=318) concluded that 3.1% of the patients with IVCFs had a recurrent PE, diagnosed radiographically.⁷

A single-center retrospective cohort study of 1731 patients with IVCFs placed for various indications showed PE in 5.6% of patients. Some embolisms were clinically suspected and not confirmed.⁸

Complications of filter placement
Complications from IVCF placement generally occur less than 3% of the time. The most common complication is postthrombotic syndrome (70%). Risks associated with IVCF placement include DVT, postthrombotic syndrome, maldeployed filter, caval thrombosis, retroperitoneal hemorrhage, malposition, filter migration, arrhythmia, insertion site complications (such as infection or hematoma), PE, myocardial infarction, and death.^1,2,5-12

Recommendations

The American College of Chest Physicians recommends considering an IVCF for patients with DVT who have a contraindication to anticoagulation, complication of anticoagulation, or recurrent thromboembolism despite adequate anticoagulation.¹²

Evidence summary

Several studies have contrasted physical examination findings associated with testicular torsion with findings related to epididymitis and torsion appendix testis. Neither the presence nor absence of any particular physical examination sign excludes the diagnosis of testicular torsion.

A consecutive case series evaluated 245 boys, newborn to 18 years of age, with acute scrotal swelling. None of the 125 subjects who had an intact cremasteric reflex had ipsilateral testicular torsion. The cremasteric reflex was absent in all 56 subjects with testicular torsion.¹ An absent cremasteric reflex in boys with acute scrotal swelling had a sensitivity of 100% (95% confidence interval [CI], 91%-100%), a specificity of 66% (95% CI, 59%-72%), and a likelihood ratio of a negative test (presence of a cremasteric reflex) of 0.01 (95% CI, 0.001-0.21).

A retrospective study reviewed the records of 90 hospitalized patients, 18 years or younger, who were discharged with a diagnosis of testicular torsion, epididymitis, or torsion appendix testis. The cremasteric reflex was absent, and testicular tenderness present, in all 13 patients with testicular torsion. The presence or absence of other physical exam findings—such as abnormal testicular lie, tender epididymis, and scrotal erythema or edema—didn’t exclude testicular torsion ( TABLE ).²

TABLE
The patients all had testicular torsion, but how helpful were the exam findings?

But cremasteric reflex and testicular torsion can coexist

Isolated case reports have demonstrated the presence of the cremasteric reflex with an eventual diagnosis of testicular torsion.^3,4 All of these studies were limited by a small number of patients and their retrospective nature.

Recommendations

When evaluating patients suspected to have testicular torsion, the European Society for Pediatric Urology (ESPU) recommends looking for absence of a cremasteric reflex and abnormal testicular position.⁵ The ESPU notes that “in many cases it is not easy to determine the cause of acute scrotum based on history and physical examination alone.”⁵ The society recommends using Doppler ultrasound as an adjunct to the history and physical.

UpToDate notes that “the diagnosis of testicular torsion can be made clinically,” but states that “radiologic evaluation (a color Doppler ultrasound or nuclear scan of the scrotum) should be undertaken if the certainty of the diagnosis is in question and the performance of imaging studies will not significantly delay treatment.”⁶

The American College of Radiology recommends color Doppler ultrasound (CDU) or radionuclide scrotal imaging (RNSI) to evaluate testicular perfusion. The group notes that “although some authors still suggest immediate surgical exploration in patients with a strong clinical impression of testicular ischemia, if either CDU or RNSI is readily available and can be performed within 30 to 60 minutes of the request to simultaneously prepare an operating room, there is ample evidence that fewer patients with infection will be operated on.”⁷

Evidence summary

Several studies have contrasted physical examination findings associated with testicular torsion with findings related to epididymitis and torsion appendix testis. Neither the presence nor absence of any particular physical examination sign excludes the diagnosis of testicular torsion.

A consecutive case series evaluated 245 boys, newborn to 18 years of age, with acute scrotal swelling. None of the 125 subjects who had an intact cremasteric reflex had ipsilateral testicular torsion. The cremasteric reflex was absent in all 56 subjects with testicular torsion.¹ An absent cremasteric reflex in boys with acute scrotal swelling had a sensitivity of 100% (95% confidence interval [CI], 91%-100%), a specificity of 66% (95% CI, 59%-72%), and a likelihood ratio of a negative test (presence of a cremasteric reflex) of 0.01 (95% CI, 0.001-0.21).

A retrospective study reviewed the records of 90 hospitalized patients, 18 years or younger, who were discharged with a diagnosis of testicular torsion, epididymitis, or torsion appendix testis. The cremasteric reflex was absent, and testicular tenderness present, in all 13 patients with testicular torsion. The presence or absence of other physical exam findings—such as abnormal testicular lie, tender epididymis, and scrotal erythema or edema—didn’t exclude testicular torsion ( TABLE ).²

TABLE
The patients all had testicular torsion, but how helpful were the exam findings?

But cremasteric reflex and testicular torsion can coexist

Isolated case reports have demonstrated the presence of the cremasteric reflex with an eventual diagnosis of testicular torsion.^3,4 All of these studies were limited by a small number of patients and their retrospective nature.

Recommendations

When evaluating patients suspected to have testicular torsion, the European Society for Pediatric Urology (ESPU) recommends looking for absence of a cremasteric reflex and abnormal testicular position.⁵ The ESPU notes that “in many cases it is not easy to determine the cause of acute scrotum based on history and physical examination alone.”⁵ The society recommends using Doppler ultrasound as an adjunct to the history and physical.

UpToDate notes that “the diagnosis of testicular torsion can be made clinically,” but states that “radiologic evaluation (a color Doppler ultrasound or nuclear scan of the scrotum) should be undertaken if the certainty of the diagnosis is in question and the performance of imaging studies will not significantly delay treatment.”⁶

The American College of Radiology recommends color Doppler ultrasound (CDU) or radionuclide scrotal imaging (RNSI) to evaluate testicular perfusion. The group notes that “although some authors still suggest immediate surgical exploration in patients with a strong clinical impression of testicular ischemia, if either CDU or RNSI is readily available and can be performed within 30 to 60 minutes of the request to simultaneously prepare an operating room, there is ample evidence that fewer patients with infection will be operated on.”⁷

Evidence summary

Several studies have contrasted physical examination findings associated with testicular torsion with findings related to epididymitis and torsion appendix testis. Neither the presence nor absence of any particular physical examination sign excludes the diagnosis of testicular torsion.

A consecutive case series evaluated 245 boys, newborn to 18 years of age, with acute scrotal swelling. None of the 125 subjects who had an intact cremasteric reflex had ipsilateral testicular torsion. The cremasteric reflex was absent in all 56 subjects with testicular torsion.¹ An absent cremasteric reflex in boys with acute scrotal swelling had a sensitivity of 100% (95% confidence interval [CI], 91%-100%), a specificity of 66% (95% CI, 59%-72%), and a likelihood ratio of a negative test (presence of a cremasteric reflex) of 0.01 (95% CI, 0.001-0.21).

A retrospective study reviewed the records of 90 hospitalized patients, 18 years or younger, who were discharged with a diagnosis of testicular torsion, epididymitis, or torsion appendix testis. The cremasteric reflex was absent, and testicular tenderness present, in all 13 patients with testicular torsion. The presence or absence of other physical exam findings—such as abnormal testicular lie, tender epididymis, and scrotal erythema or edema—didn’t exclude testicular torsion ( TABLE ).²

TABLE
The patients all had testicular torsion, but how helpful were the exam findings?

But cremasteric reflex and testicular torsion can coexist

Isolated case reports have demonstrated the presence of the cremasteric reflex with an eventual diagnosis of testicular torsion.^3,4 All of these studies were limited by a small number of patients and their retrospective nature.

Recommendations

When evaluating patients suspected to have testicular torsion, the European Society for Pediatric Urology (ESPU) recommends looking for absence of a cremasteric reflex and abnormal testicular position.⁵ The ESPU notes that “in many cases it is not easy to determine the cause of acute scrotum based on history and physical examination alone.”⁵ The society recommends using Doppler ultrasound as an adjunct to the history and physical.

UpToDate notes that “the diagnosis of testicular torsion can be made clinically,” but states that “radiologic evaluation (a color Doppler ultrasound or nuclear scan of the scrotum) should be undertaken if the certainty of the diagnosis is in question and the performance of imaging studies will not significantly delay treatment.”⁶

The American College of Radiology recommends color Doppler ultrasound (CDU) or radionuclide scrotal imaging (RNSI) to evaluate testicular perfusion. The group notes that “although some authors still suggest immediate surgical exploration in patients with a strong clinical impression of testicular ischemia, if either CDU or RNSI is readily available and can be performed within 30 to 60 minutes of the request to simultaneously prepare an operating room, there is ample evidence that fewer patients with infection will be operated on.”⁷

Evidence summary

Our comprehensive literature search found no systematic reviews, randomized trials, or prospective cohort studies that answer this question. The differential diagnosis of clinical hair loss is large (TABLE). We reviewed indirect evidence and expert opinion to answer this Clinical Inquiry.

Clues in the history

A detailed history—including medication use, systemic illness, endocrine dysfunction, hair care practices, severe diet restriction, and family history—is key to establishing an accurate diagnosis of alopecia.¹ Other significant considerations include the onset, duration, and pattern of hair loss; whether hair is broken or shed at the root; and whether shedding or thinning has increased.^1,2 It’s also important to ascertain whether hair loss is limited to the scalp or affects other areas of the body.

A family history of alopecia areata or androgenic alopecia can point to a genetic cause. Acne or abnormal menses can indicate androgen excess, suggesting androgenic alopecia. Positive answers to thyroid screening questions can point to hypothyroidism, and abnormal diet patterns can suggest iron-deficiency anemia. Unusual hair care practices can cause traction alopecia.¹

TABLE
Causes of nonscarring alopecia

3 stages of the physical exam

All hair-bearing sites should be examined. Clinical examination should be performed in 3 stages:^1,2

• Inspect the scalp for inflammation, scale, and erythema to determine whether scarring is present.
• Examine the hair density and distribution pattern.
• Study the hair shaft quality, looking at caliber, fragility, length, and shape.

The “pull test” is often used to assess ongoing hair loss. If more than 10% of hairs are pulled away from the scalp, the test is positive, suggesting active hair shedding.¹

Beyond the history and physical

Ancillary laboratory evaluation is sometimes necessary if the diagnosis remains unclear.^1,2 Serum ferritin or a complete blood count can be useful to look for iron-deficiency anemia; a thyroid-stimulating hormone test can rule out hypothyroidism.³ According to 1 small study of 50 women with diffuse alopecia, thyroid tests are not routinely warranted without supportive clinical signs.⁴

Check free testosterone, androstenedione, and dehydroepiandrosterone if virilizing signs are present, to assess hyperandrogenism.^1,3 Serum prolactin can be useful if the patient has galactorrhea.⁵ Also, consider a Venereal Disease Research Laboratory test to rule out syphilis.^2,6

No evidence suggests that low serum zinc concentrations cause hair loss. In fact, excessive intake of nutritional supplements may lead to hair loss and aren’t recommended in the absence of a proven deficiency.⁷

If a patient has scarring alopecia, a scalp biopsy is almost always necessary to make a diagnosis.¹ Usually a punch biopsy is sufficient, but it should be no smaller than 4 mm. The preferred location is the central scalp in an area representative of the hair loss.^1,5

Recommendations

The University of Texas Family Nurse Practitioner Program recommends a thorough history and physical examination and, if indicated, selected laboratory evaluation.⁶ The program states that the Women’s Androgenetic Alopecia Quality of Life (WAA-QOL) Questionnaire is useful in evaluating health-related quality of life specific to women.

The American Hair Loss Association recommends checking some screening labs on women with hair loss, but states that the diagnosis is usually a process of elimination as many of the laboratory tests mentioned above will come back in the normal range.⁸

Evidence summary

Our comprehensive literature search found no systematic reviews, randomized trials, or prospective cohort studies that answer this question. The differential diagnosis of clinical hair loss is large (TABLE). We reviewed indirect evidence and expert opinion to answer this Clinical Inquiry.

Clues in the history

A detailed history—including medication use, systemic illness, endocrine dysfunction, hair care practices, severe diet restriction, and family history—is key to establishing an accurate diagnosis of alopecia.¹ Other significant considerations include the onset, duration, and pattern of hair loss; whether hair is broken or shed at the root; and whether shedding or thinning has increased.^1,2 It’s also important to ascertain whether hair loss is limited to the scalp or affects other areas of the body.

A family history of alopecia areata or androgenic alopecia can point to a genetic cause. Acne or abnormal menses can indicate androgen excess, suggesting androgenic alopecia. Positive answers to thyroid screening questions can point to hypothyroidism, and abnormal diet patterns can suggest iron-deficiency anemia. Unusual hair care practices can cause traction alopecia.¹

TABLE
Causes of nonscarring alopecia

3 stages of the physical exam

All hair-bearing sites should be examined. Clinical examination should be performed in 3 stages:^1,2

• Inspect the scalp for inflammation, scale, and erythema to determine whether scarring is present.
• Examine the hair density and distribution pattern.
• Study the hair shaft quality, looking at caliber, fragility, length, and shape.

The “pull test” is often used to assess ongoing hair loss. If more than 10% of hairs are pulled away from the scalp, the test is positive, suggesting active hair shedding.¹

Beyond the history and physical

Ancillary laboratory evaluation is sometimes necessary if the diagnosis remains unclear.^1,2 Serum ferritin or a complete blood count can be useful to look for iron-deficiency anemia; a thyroid-stimulating hormone test can rule out hypothyroidism.³ According to 1 small study of 50 women with diffuse alopecia, thyroid tests are not routinely warranted without supportive clinical signs.⁴

Check free testosterone, androstenedione, and dehydroepiandrosterone if virilizing signs are present, to assess hyperandrogenism.^1,3 Serum prolactin can be useful if the patient has galactorrhea.⁵ Also, consider a Venereal Disease Research Laboratory test to rule out syphilis.^2,6

No evidence suggests that low serum zinc concentrations cause hair loss. In fact, excessive intake of nutritional supplements may lead to hair loss and aren’t recommended in the absence of a proven deficiency.⁷

If a patient has scarring alopecia, a scalp biopsy is almost always necessary to make a diagnosis.¹ Usually a punch biopsy is sufficient, but it should be no smaller than 4 mm. The preferred location is the central scalp in an area representative of the hair loss.^1,5

Recommendations

The University of Texas Family Nurse Practitioner Program recommends a thorough history and physical examination and, if indicated, selected laboratory evaluation.⁶ The program states that the Women’s Androgenetic Alopecia Quality of Life (WAA-QOL) Questionnaire is useful in evaluating health-related quality of life specific to women.

The American Hair Loss Association recommends checking some screening labs on women with hair loss, but states that the diagnosis is usually a process of elimination as many of the laboratory tests mentioned above will come back in the normal range.⁸

Evidence summary

Our comprehensive literature search found no systematic reviews, randomized trials, or prospective cohort studies that answer this question. The differential diagnosis of clinical hair loss is large (TABLE). We reviewed indirect evidence and expert opinion to answer this Clinical Inquiry.

Clues in the history

A detailed history—including medication use, systemic illness, endocrine dysfunction, hair care practices, severe diet restriction, and family history—is key to establishing an accurate diagnosis of alopecia.¹ Other significant considerations include the onset, duration, and pattern of hair loss; whether hair is broken or shed at the root; and whether shedding or thinning has increased.^1,2 It’s also important to ascertain whether hair loss is limited to the scalp or affects other areas of the body.

A family history of alopecia areata or androgenic alopecia can point to a genetic cause. Acne or abnormal menses can indicate androgen excess, suggesting androgenic alopecia. Positive answers to thyroid screening questions can point to hypothyroidism, and abnormal diet patterns can suggest iron-deficiency anemia. Unusual hair care practices can cause traction alopecia.¹

TABLE
Causes of nonscarring alopecia

3 stages of the physical exam

All hair-bearing sites should be examined. Clinical examination should be performed in 3 stages:^1,2

• Inspect the scalp for inflammation, scale, and erythema to determine whether scarring is present.
• Examine the hair density and distribution pattern.
• Study the hair shaft quality, looking at caliber, fragility, length, and shape.

The “pull test” is often used to assess ongoing hair loss. If more than 10% of hairs are pulled away from the scalp, the test is positive, suggesting active hair shedding.¹

Beyond the history and physical

Ancillary laboratory evaluation is sometimes necessary if the diagnosis remains unclear.^1,2 Serum ferritin or a complete blood count can be useful to look for iron-deficiency anemia; a thyroid-stimulating hormone test can rule out hypothyroidism.³ According to 1 small study of 50 women with diffuse alopecia, thyroid tests are not routinely warranted without supportive clinical signs.⁴

Check free testosterone, androstenedione, and dehydroepiandrosterone if virilizing signs are present, to assess hyperandrogenism.^1,3 Serum prolactin can be useful if the patient has galactorrhea.⁵ Also, consider a Venereal Disease Research Laboratory test to rule out syphilis.^2,6

No evidence suggests that low serum zinc concentrations cause hair loss. In fact, excessive intake of nutritional supplements may lead to hair loss and aren’t recommended in the absence of a proven deficiency.⁷

If a patient has scarring alopecia, a scalp biopsy is almost always necessary to make a diagnosis.¹ Usually a punch biopsy is sufficient, but it should be no smaller than 4 mm. The preferred location is the central scalp in an area representative of the hair loss.^1,5

Recommendations

The University of Texas Family Nurse Practitioner Program recommends a thorough history and physical examination and, if indicated, selected laboratory evaluation.⁶ The program states that the Women’s Androgenetic Alopecia Quality of Life (WAA-QOL) Questionnaire is useful in evaluating health-related quality of life specific to women.

The American Hair Loss Association recommends checking some screening labs on women with hair loss, but states that the diagnosis is usually a process of elimination as many of the laboratory tests mentioned above will come back in the normal range.⁸