Clinical Inquiries

Evidence summary

The low incidence of ovarian cancer in the general population (40/100,000) makes it a challenge for successful screening. Current screening methods include pelvic examination, CA-125 levels, TVU, or a combination of modalities. Very limited data exist on the usefulness of the bimanual pelvic exam. Palpation can detect some ovarian cancers, but those cancers are usually advanced and associated with a poor prognosis.¹ In general, pelvic exam is not thought to be a useful screening procedure for ovarian cancer in asymptomatic women.

Estimates of the performance of other screening tests are extremely imprecise due to study limitations.² CA-125 has a reported sensitivity of about 80%, a high specificity of 98%–99%, and a false-positive rate of 0.1%–0.6%. Ultrasound has a sensitivity approaching 100%, a lower specificity, and a higher false-positive rate of 1.2%–2.5%. Using ultrasound, more cancers would be identified, but more women would face unnecessary intervention or surgery. Use of multimodal screening (CA-125 followed by TVU if abnormal) can increase specificity to 99.9% but has a lower sensitivity (58%–79%).³ Use of multimodal screening results in a higher rate of false negatives and could therefore create a false sense of security.

Between 5%–17% of women who undergo initial screening with ultrasound and 0.9%–4% of those who undergo multimodal screening will be recalled for further testing, potentially resulting in distress and anxiety. With ultrasound screening, 7–60 women will undergo diagnostic surgery for every 1 cancer detected. Using multimodal screening, 2.5–15 women will undergo diagnostic surgery for every cancer detected.

Before screening is implemented, there should be evidence that early detection and treatment of the disease results in improved outcomes. Several ongoing randomized controlled trials address screening of average-risk women, including one sponsored by the National Institutes of Health (NIH).⁴ There is indirect evidence that early detection prolongs survival, as well as evidence that screening results in an increase in diagnosing a tumor at stage 1.²

A large pilot study showed improved median survival in a screened group compared with a control group (72.9 months vs 41.8 months), but there was no significant difference in either mortality from ovarian cancer or all-cause mortality.³ This is consistent with earlier evidence that screening brings forward the diagnosis of ovarian cancer by about 8 months,¹ but raises the possibility that earlier diagnosis may simply reflect a lead-time bias without any actual improvement in outcome.

Women with 2 or more first-degree family members with ovarian cancer are at risk for one of the rare hereditary cancer syndromes, with lifetime risk of ovarian cancer of 40%. Although there is interest in identifying and screening these very high-risk women, there is no evidence that screening benefits this group in terms of median

Recommendations from others

No organization currently recommends routine ovarian cancer screening of average-risk women. The US Preventive Services Task Force (USPSTF),¹ American College of Obstetricians and Gynecologists (ACOG), American College of Physicians,^5,6 and the Canadian Task Force on Preventive Health Care (CTF)⁷ all recommend against routine use of serum tumor markers or ultrasound for women at average risk.

USPSTF and CTF found insufficient evidence for or against screening women at increased risk. An NIH Consensus Conference recommends comprehensive family history and annual pelvic exam for all women, referral to a specialist for risk counseling for women with 2 or more first-degree relatives, and annual screening with pelvic examination, CA-125, and TVS in women with known hereditary ovarian cancer syndrome.⁸

ACOG recommends an annual pelvic examination for all women as part of routine preventive care.⁹ While the USPSTF does not recommend the use of pelvic exam for ovarian cancer screening, it states it is prudent to do a bimanual examination when performing a gynecologic examination for other reasons.^1,9

Evidence summary

The low incidence of ovarian cancer in the general population (40/100,000) makes it a challenge for successful screening. Current screening methods include pelvic examination, CA-125 levels, TVU, or a combination of modalities. Very limited data exist on the usefulness of the bimanual pelvic exam. Palpation can detect some ovarian cancers, but those cancers are usually advanced and associated with a poor prognosis.¹ In general, pelvic exam is not thought to be a useful screening procedure for ovarian cancer in asymptomatic women.

Estimates of the performance of other screening tests are extremely imprecise due to study limitations.² CA-125 has a reported sensitivity of about 80%, a high specificity of 98%–99%, and a false-positive rate of 0.1%–0.6%. Ultrasound has a sensitivity approaching 100%, a lower specificity, and a higher false-positive rate of 1.2%–2.5%. Using ultrasound, more cancers would be identified, but more women would face unnecessary intervention or surgery. Use of multimodal screening (CA-125 followed by TVU if abnormal) can increase specificity to 99.9% but has a lower sensitivity (58%–79%).³ Use of multimodal screening results in a higher rate of false negatives and could therefore create a false sense of security.

Between 5%–17% of women who undergo initial screening with ultrasound and 0.9%–4% of those who undergo multimodal screening will be recalled for further testing, potentially resulting in distress and anxiety. With ultrasound screening, 7–60 women will undergo diagnostic surgery for every 1 cancer detected. Using multimodal screening, 2.5–15 women will undergo diagnostic surgery for every cancer detected.

Before screening is implemented, there should be evidence that early detection and treatment of the disease results in improved outcomes. Several ongoing randomized controlled trials address screening of average-risk women, including one sponsored by the National Institutes of Health (NIH).⁴ There is indirect evidence that early detection prolongs survival, as well as evidence that screening results in an increase in diagnosing a tumor at stage 1.²

A large pilot study showed improved median survival in a screened group compared with a control group (72.9 months vs 41.8 months), but there was no significant difference in either mortality from ovarian cancer or all-cause mortality.³ This is consistent with earlier evidence that screening brings forward the diagnosis of ovarian cancer by about 8 months,¹ but raises the possibility that earlier diagnosis may simply reflect a lead-time bias without any actual improvement in outcome.

Women with 2 or more first-degree family members with ovarian cancer are at risk for one of the rare hereditary cancer syndromes, with lifetime risk of ovarian cancer of 40%. Although there is interest in identifying and screening these very high-risk women, there is no evidence that screening benefits this group in terms of median

Recommendations from others

No organization currently recommends routine ovarian cancer screening of average-risk women. The US Preventive Services Task Force (USPSTF),¹ American College of Obstetricians and Gynecologists (ACOG), American College of Physicians,^5,6 and the Canadian Task Force on Preventive Health Care (CTF)⁷ all recommend against routine use of serum tumor markers or ultrasound for women at average risk.

USPSTF and CTF found insufficient evidence for or against screening women at increased risk. An NIH Consensus Conference recommends comprehensive family history and annual pelvic exam for all women, referral to a specialist for risk counseling for women with 2 or more first-degree relatives, and annual screening with pelvic examination, CA-125, and TVS in women with known hereditary ovarian cancer syndrome.⁸

ACOG recommends an annual pelvic examination for all women as part of routine preventive care.⁹ While the USPSTF does not recommend the use of pelvic exam for ovarian cancer screening, it states it is prudent to do a bimanual examination when performing a gynecologic examination for other reasons.^1,9

Evidence summary

The low incidence of ovarian cancer in the general population (40/100,000) makes it a challenge for successful screening. Current screening methods include pelvic examination, CA-125 levels, TVU, or a combination of modalities. Very limited data exist on the usefulness of the bimanual pelvic exam. Palpation can detect some ovarian cancers, but those cancers are usually advanced and associated with a poor prognosis.¹ In general, pelvic exam is not thought to be a useful screening procedure for ovarian cancer in asymptomatic women.

Estimates of the performance of other screening tests are extremely imprecise due to study limitations.² CA-125 has a reported sensitivity of about 80%, a high specificity of 98%–99%, and a false-positive rate of 0.1%–0.6%. Ultrasound has a sensitivity approaching 100%, a lower specificity, and a higher false-positive rate of 1.2%–2.5%. Using ultrasound, more cancers would be identified, but more women would face unnecessary intervention or surgery. Use of multimodal screening (CA-125 followed by TVU if abnormal) can increase specificity to 99.9% but has a lower sensitivity (58%–79%).³ Use of multimodal screening results in a higher rate of false negatives and could therefore create a false sense of security.

Between 5%–17% of women who undergo initial screening with ultrasound and 0.9%–4% of those who undergo multimodal screening will be recalled for further testing, potentially resulting in distress and anxiety. With ultrasound screening, 7–60 women will undergo diagnostic surgery for every 1 cancer detected. Using multimodal screening, 2.5–15 women will undergo diagnostic surgery for every cancer detected.

Before screening is implemented, there should be evidence that early detection and treatment of the disease results in improved outcomes. Several ongoing randomized controlled trials address screening of average-risk women, including one sponsored by the National Institutes of Health (NIH).⁴ There is indirect evidence that early detection prolongs survival, as well as evidence that screening results in an increase in diagnosing a tumor at stage 1.²

A large pilot study showed improved median survival in a screened group compared with a control group (72.9 months vs 41.8 months), but there was no significant difference in either mortality from ovarian cancer or all-cause mortality.³ This is consistent with earlier evidence that screening brings forward the diagnosis of ovarian cancer by about 8 months,¹ but raises the possibility that earlier diagnosis may simply reflect a lead-time bias without any actual improvement in outcome.

Women with 2 or more first-degree family members with ovarian cancer are at risk for one of the rare hereditary cancer syndromes, with lifetime risk of ovarian cancer of 40%. Although there is interest in identifying and screening these very high-risk women, there is no evidence that screening benefits this group in terms of median

Recommendations from others

No organization currently recommends routine ovarian cancer screening of average-risk women. The US Preventive Services Task Force (USPSTF),¹ American College of Obstetricians and Gynecologists (ACOG), American College of Physicians,^5,6 and the Canadian Task Force on Preventive Health Care (CTF)⁷ all recommend against routine use of serum tumor markers or ultrasound for women at average risk.

USPSTF and CTF found insufficient evidence for or against screening women at increased risk. An NIH Consensus Conference recommends comprehensive family history and annual pelvic exam for all women, referral to a specialist for risk counseling for women with 2 or more first-degree relatives, and annual screening with pelvic examination, CA-125, and TVS in women with known hereditary ovarian cancer syndrome.⁸

ACOG recommends an annual pelvic examination for all women as part of routine preventive care.⁹ While the USPSTF does not recommend the use of pelvic exam for ovarian cancer screening, it states it is prudent to do a bimanual examination when performing a gynecologic examination for other reasons.^1,9

Evidence summary

Although breastfeeding jaundice is a benign entity, other risk factors for bilirubin toxicity can coexist. These include jaundice in the first day of life, previously jaundiced sibling, early gestational age, significant bruising or cephalohematoma, Rh and ABO incompatibility, G6PD deficiency, and elevated hour-specific serum or transcutaneous bilirubin levels.^2,3

Late initiation of breastfeeding and temporary cessation or supplementation of breastfeeding increase the likelihood of premature breastfeeding termination.⁴ In a prospective cohort study of 138 breastfed term infants, more than twice as many mothers of jaundiced infants had stopped breastfeeding compared with mothers of nonjaundiced infants, at the end of 1 month (42% vs 19%; number needed to harm [NNH]=4; P<.01). In addition, 64% of the jaundiced infants whose nursing had been interrupted in the hospital had stopped breastfeeding by 1 month, compared with only 36% of those who had no interruption (relative risk [RR]=1.8; P<.05; NNH=4).⁵

Whether they require phototherapy or not, continuing breastfeeding in jaundiced infants is not associated with adverse outcomes. In a prospective cohort study of 163 healthy, jaundiced newborn infants undergoing phototherapy (total serum bilirubin ≥17 mg/dL), exclusively breastfed infants had slower response to phototherapy in the first 24 hours than formulafed or formula-supplemented infants (bilirubin decreases of 17.1% vs 18% and 22.9%, respectively; P=.03). However, there were no significant differences in total length of phototherapy among the 3 groups (phototherapy time of 64.5 hours vs 54.1 hours and 54.9 hours, respectively; P=.06).⁶

In a randomized, nonblinded clinical trial, 125 jaundiced breastfed newborns (total serum bilirubin level of ≥17mg/dL) were assigned to 4 treatment groups: (1) continue breastfeeding and observe; (2) discontinue breastfeeding, substitute with formula; (3) discontinue breastfeeding, substitute with formula, and administer phototherapy; and (4) continue breastfeeding, administer phototherapy. The study did not find a clinically significant difference in serum bilirubin reduction to normal levels at 48 hours between breastfed and bottle-fed groups undergoing phototherapy (RR=1.07; 95% confidence interval [CI], 0.6–1.92; P=.818), or between breastfed and bottle-fed groups who did not have phototherapy (RR not calculated; P=.051). No patient required exchange transfusion, and in no case did total serum bilirubin exceed 23 mg/dL.⁷

Recommendations from others

The American Academy of Pediatrics (AAP) has reported numerous positive health outcomes in infants who are breastfed, including reduced incidence and less-severe diarrhea; lower incidence of otitis media, fewer respiratory infections; and lower incidence of bacteremia, bacterial meningitis, botulism, urinary tract infections and necrotizing enterocolitis.

In addition, they reported association between breastfeeding and enhanced cognitive development; and decreased incidence in sudden infant death syndrome, insulin-dependent diabetes mellitus, atopy, and inflammatory bowel diseases. They noted maternal benefits including less postpartum bleeding and lactational amenorrhea; more rapid postpartum weight loss and improved bone remineralization; and reduced risk of ovarian cancer and premenopausal breast cancer.¹

The AAP discourages the termination of breastfeeding in jaundiced healthy term newborns and encourages continued and frequent breastfeeding (at least 8 to 10 times every 24 hours), encouraging physician’s judgment and patient’s preferences to determine final treatment options for breastfeeding jaundiced newborns.²

Evidence summary

Although breastfeeding jaundice is a benign entity, other risk factors for bilirubin toxicity can coexist. These include jaundice in the first day of life, previously jaundiced sibling, early gestational age, significant bruising or cephalohematoma, Rh and ABO incompatibility, G6PD deficiency, and elevated hour-specific serum or transcutaneous bilirubin levels.^2,3

Late initiation of breastfeeding and temporary cessation or supplementation of breastfeeding increase the likelihood of premature breastfeeding termination.⁴ In a prospective cohort study of 138 breastfed term infants, more than twice as many mothers of jaundiced infants had stopped breastfeeding compared with mothers of nonjaundiced infants, at the end of 1 month (42% vs 19%; number needed to harm [NNH]=4; P<.01). In addition, 64% of the jaundiced infants whose nursing had been interrupted in the hospital had stopped breastfeeding by 1 month, compared with only 36% of those who had no interruption (relative risk [RR]=1.8; P<.05; NNH=4).⁵

Whether they require phototherapy or not, continuing breastfeeding in jaundiced infants is not associated with adverse outcomes. In a prospective cohort study of 163 healthy, jaundiced newborn infants undergoing phototherapy (total serum bilirubin ≥17 mg/dL), exclusively breastfed infants had slower response to phototherapy in the first 24 hours than formulafed or formula-supplemented infants (bilirubin decreases of 17.1% vs 18% and 22.9%, respectively; P=.03). However, there were no significant differences in total length of phototherapy among the 3 groups (phototherapy time of 64.5 hours vs 54.1 hours and 54.9 hours, respectively; P=.06).⁶

In a randomized, nonblinded clinical trial, 125 jaundiced breastfed newborns (total serum bilirubin level of ≥17mg/dL) were assigned to 4 treatment groups: (1) continue breastfeeding and observe; (2) discontinue breastfeeding, substitute with formula; (3) discontinue breastfeeding, substitute with formula, and administer phototherapy; and (4) continue breastfeeding, administer phototherapy. The study did not find a clinically significant difference in serum bilirubin reduction to normal levels at 48 hours between breastfed and bottle-fed groups undergoing phototherapy (RR=1.07; 95% confidence interval [CI], 0.6–1.92; P=.818), or between breastfed and bottle-fed groups who did not have phototherapy (RR not calculated; P=.051). No patient required exchange transfusion, and in no case did total serum bilirubin exceed 23 mg/dL.⁷

Recommendations from others

The American Academy of Pediatrics (AAP) has reported numerous positive health outcomes in infants who are breastfed, including reduced incidence and less-severe diarrhea; lower incidence of otitis media, fewer respiratory infections; and lower incidence of bacteremia, bacterial meningitis, botulism, urinary tract infections and necrotizing enterocolitis.

In addition, they reported association between breastfeeding and enhanced cognitive development; and decreased incidence in sudden infant death syndrome, insulin-dependent diabetes mellitus, atopy, and inflammatory bowel diseases. They noted maternal benefits including less postpartum bleeding and lactational amenorrhea; more rapid postpartum weight loss and improved bone remineralization; and reduced risk of ovarian cancer and premenopausal breast cancer.¹

The AAP discourages the termination of breastfeeding in jaundiced healthy term newborns and encourages continued and frequent breastfeeding (at least 8 to 10 times every 24 hours), encouraging physician’s judgment and patient’s preferences to determine final treatment options for breastfeeding jaundiced newborns.²

Evidence summary

Although breastfeeding jaundice is a benign entity, other risk factors for bilirubin toxicity can coexist. These include jaundice in the first day of life, previously jaundiced sibling, early gestational age, significant bruising or cephalohematoma, Rh and ABO incompatibility, G6PD deficiency, and elevated hour-specific serum or transcutaneous bilirubin levels.^2,3

Late initiation of breastfeeding and temporary cessation or supplementation of breastfeeding increase the likelihood of premature breastfeeding termination.⁴ In a prospective cohort study of 138 breastfed term infants, more than twice as many mothers of jaundiced infants had stopped breastfeeding compared with mothers of nonjaundiced infants, at the end of 1 month (42% vs 19%; number needed to harm [NNH]=4; P<.01). In addition, 64% of the jaundiced infants whose nursing had been interrupted in the hospital had stopped breastfeeding by 1 month, compared with only 36% of those who had no interruption (relative risk [RR]=1.8; P<.05; NNH=4).⁵

Whether they require phototherapy or not, continuing breastfeeding in jaundiced infants is not associated with adverse outcomes. In a prospective cohort study of 163 healthy, jaundiced newborn infants undergoing phototherapy (total serum bilirubin ≥17 mg/dL), exclusively breastfed infants had slower response to phototherapy in the first 24 hours than formulafed or formula-supplemented infants (bilirubin decreases of 17.1% vs 18% and 22.9%, respectively; P=.03). However, there were no significant differences in total length of phototherapy among the 3 groups (phototherapy time of 64.5 hours vs 54.1 hours and 54.9 hours, respectively; P=.06).⁶

In a randomized, nonblinded clinical trial, 125 jaundiced breastfed newborns (total serum bilirubin level of ≥17mg/dL) were assigned to 4 treatment groups: (1) continue breastfeeding and observe; (2) discontinue breastfeeding, substitute with formula; (3) discontinue breastfeeding, substitute with formula, and administer phototherapy; and (4) continue breastfeeding, administer phototherapy. The study did not find a clinically significant difference in serum bilirubin reduction to normal levels at 48 hours between breastfed and bottle-fed groups undergoing phototherapy (RR=1.07; 95% confidence interval [CI], 0.6–1.92; P=.818), or between breastfed and bottle-fed groups who did not have phototherapy (RR not calculated; P=.051). No patient required exchange transfusion, and in no case did total serum bilirubin exceed 23 mg/dL.⁷

Recommendations from others

The American Academy of Pediatrics (AAP) has reported numerous positive health outcomes in infants who are breastfed, including reduced incidence and less-severe diarrhea; lower incidence of otitis media, fewer respiratory infections; and lower incidence of bacteremia, bacterial meningitis, botulism, urinary tract infections and necrotizing enterocolitis.

In addition, they reported association between breastfeeding and enhanced cognitive development; and decreased incidence in sudden infant death syndrome, insulin-dependent diabetes mellitus, atopy, and inflammatory bowel diseases. They noted maternal benefits including less postpartum bleeding and lactational amenorrhea; more rapid postpartum weight loss and improved bone remineralization; and reduced risk of ovarian cancer and premenopausal breast cancer.¹

The AAP discourages the termination of breastfeeding in jaundiced healthy term newborns and encourages continued and frequent breastfeeding (at least 8 to 10 times every 24 hours), encouraging physician’s judgment and patient’s preferences to determine final treatment options for breastfeeding jaundiced newborns.²

Evidence summary

The prevalence of urinary tract infection in childhood has been estimated to be roughly 1%.¹ For those children with asymptomatic bacteriuria, fewer than 10% progress to symptomatic urinary tract infections.² The prevalence of other glomelonephropathies is <0.05%.^3,4 Currently vailable screening urinalyses using chemical dipstick testing have reported sensitivities ranging from 53% to 93% and specificities of 72% to 98% for detecting significant bacteriuria.⁵ All positive screening tests for acteriuria require confirmation by standard urine culture.

No prospective randomized trials of screening urinalysis in childhood have been published to date. Expert opinion varies as to the necessity of screening urinalysis. No prospective randomized trials demonstrate improved outcomes, and limited evidence suggests that detection and treatment of asymptomatic bacteriuria improves long-term outcomes such as renal scarring, hypertension, or pyelone phritis.⁶

Recommendations from others

The American Academy of Pediatrics recommends 1 screening dipstick urinalysis at age 5.⁷ The American Academy of Family Physicians,⁸ Bright Futures,⁹ Canadian Task Force on the Periodic Health xamination,¹⁰ and the United States Preventive Services Task Force¹¹ do not recommend screening for asymptomatic bacteriuria in children. The Institute for Clinical Systems Improvement recommends that consideration be given to eliminating routine urinalyses in asymptomatic children.¹²

Evidence summary

The prevalence of urinary tract infection in childhood has been estimated to be roughly 1%.¹ For those children with asymptomatic bacteriuria, fewer than 10% progress to symptomatic urinary tract infections.² The prevalence of other glomelonephropathies is <0.05%.^3,4 Currently vailable screening urinalyses using chemical dipstick testing have reported sensitivities ranging from 53% to 93% and specificities of 72% to 98% for detecting significant bacteriuria.⁵ All positive screening tests for acteriuria require confirmation by standard urine culture.

No prospective randomized trials of screening urinalysis in childhood have been published to date. Expert opinion varies as to the necessity of screening urinalysis. No prospective randomized trials demonstrate improved outcomes, and limited evidence suggests that detection and treatment of asymptomatic bacteriuria improves long-term outcomes such as renal scarring, hypertension, or pyelone phritis.⁶

Recommendations from others

The American Academy of Pediatrics recommends 1 screening dipstick urinalysis at age 5.⁷ The American Academy of Family Physicians,⁸ Bright Futures,⁹ Canadian Task Force on the Periodic Health xamination,¹⁰ and the United States Preventive Services Task Force¹¹ do not recommend screening for asymptomatic bacteriuria in children. The Institute for Clinical Systems Improvement recommends that consideration be given to eliminating routine urinalyses in asymptomatic children.¹²

Evidence summary

The prevalence of urinary tract infection in childhood has been estimated to be roughly 1%.¹ For those children with asymptomatic bacteriuria, fewer than 10% progress to symptomatic urinary tract infections.² The prevalence of other glomelonephropathies is <0.05%.^3,4 Currently vailable screening urinalyses using chemical dipstick testing have reported sensitivities ranging from 53% to 93% and specificities of 72% to 98% for detecting significant bacteriuria.⁵ All positive screening tests for acteriuria require confirmation by standard urine culture.

No prospective randomized trials of screening urinalysis in childhood have been published to date. Expert opinion varies as to the necessity of screening urinalysis. No prospective randomized trials demonstrate improved outcomes, and limited evidence suggests that detection and treatment of asymptomatic bacteriuria improves long-term outcomes such as renal scarring, hypertension, or pyelone phritis.⁶

Recommendations from others

The American Academy of Pediatrics recommends 1 screening dipstick urinalysis at age 5.⁷ The American Academy of Family Physicians,⁸ Bright Futures,⁹ Canadian Task Force on the Periodic Health xamination,¹⁰ and the United States Preventive Services Task Force¹¹ do not recommend screening for asymptomatic bacteriuria in children. The Institute for Clinical Systems Improvement recommends that consideration be given to eliminating routine urinalyses in asymptomatic children.¹²

Evidence summary

A well-done systematic review of 12 trials assessing the efficacy of stimulant therapy in the treatment of adult ADHD did not find sufficient evidence that stimulants were effective.¹ Significant heterogeneity and poor reporting of methodology was seen among the studies.

The 1 study rated as high-quality was a 7-week randomized controlled trial using a crossover comparison of methylphenidate and placebo.² There was a favorable response in 78% (18/23) of subjects while takin methylphenidate, in contrast to 4% (1/23) while taking placebo (number needed to treat [NNT]=1.4; P<.0001). A favorable response was assessed by the Clinical Global Impression Scale, a measure of illness severity and improvement, and a >30% reduction in symptoms as measured by the ADHD Rating Scale. A more recent, but less rigorous, systematic review identified 15 studies of stimulant efficacy in adults.³ Researchers concluded that under controlled conditions, stimulants are efficacious in the treatment of ADHD in adults. The rate of response among the studies ranged from 25% to 78%.

One of the better studies in this review was a randomized, double-blind, 3-phase crossover study of dextroamphetamine, modafinil (a drug used to treat narcolepsy), and placebo.⁴ Each phase was 2 weeks long, with a 4-day washout in between. A favorable response was defined as a reduction of ADHD symptoms by at least 30% on the DSM-IV ADHD Behavior Checklist for Adults. Dextroamphetamine and modafinil showed the same response rate in 10 of 21 patients. Both treatments had a significant improvement over placebo (P<.001). It was unclear from the study what percentage of subjects responded to placebo.

A similar study compared dextroamphetamine, guanfacine (an antihypertensive agent), and placebo in 17 patients.⁵ On the DSM-IV ADHD Behavior Checklist for Adults, subjects taking dextroamphetamine or guanfacine reported similar decreases in mean ADHD scores compared with placebo (24 vs 22 vs 30; P<.05). They did not report the number of subjects who had a 30% reduction in symptoms. Of note: at the end of the study but prior to unblinding, subjects were asked which medication they preferred. Twelve subjects chose dextroamphetamine, 4 chose guanfacine, and 1 chose placebo. Subjects’ stated reason for choosing dextroamphetamine was the positive effect it had on their motivation.

Another study included in this review was a randomized controlled trial of mixed amphetamine salts. Of the 27 adults who completed the study, 19 (70%) responded favorably to mixed amphetamine salts compared with 2 (7.4%) receiving placebo (NNT=1.6; P<.001).⁶ Favorable response was defined as more than a 30% reduction of symptoms on the ADHD Rating Scale. Not included in either review was a 7-week randomized controlled trial comparing methylphenidate with sustained-release buproprion.⁷ Thirty out of 37 subjects completed at least 1 week of the study. The primary indicator of a favorable response was the Clinical Global Impression Scale. The rate of response was 50% for methylphenidate, 64% for sustained-release buproprion, and 27% for placebo (P<.14).

Recommendations from others

The American Academy of Child and Adolescent Psychiatry⁸ concluded that stimulant medication can be used to treat adults who have been carefully evaluated. They recommend starting methylphenidate, dextroamphetamine, or mixed amphetamine salts according to patient and clinician preference (Table). They do not recommend the use of pemoline due to the potential for hepatic failure.

TABLE
Stimulants used to treat ADHD in adults

Evidence summary

A well-done systematic review of 12 trials assessing the efficacy of stimulant therapy in the treatment of adult ADHD did not find sufficient evidence that stimulants were effective.¹ Significant heterogeneity and poor reporting of methodology was seen among the studies.

The 1 study rated as high-quality was a 7-week randomized controlled trial using a crossover comparison of methylphenidate and placebo.² There was a favorable response in 78% (18/23) of subjects while takin methylphenidate, in contrast to 4% (1/23) while taking placebo (number needed to treat [NNT]=1.4; P<.0001). A favorable response was assessed by the Clinical Global Impression Scale, a measure of illness severity and improvement, and a >30% reduction in symptoms as measured by the ADHD Rating Scale. A more recent, but less rigorous, systematic review identified 15 studies of stimulant efficacy in adults.³ Researchers concluded that under controlled conditions, stimulants are efficacious in the treatment of ADHD in adults. The rate of response among the studies ranged from 25% to 78%.

One of the better studies in this review was a randomized, double-blind, 3-phase crossover study of dextroamphetamine, modafinil (a drug used to treat narcolepsy), and placebo.⁴ Each phase was 2 weeks long, with a 4-day washout in between. A favorable response was defined as a reduction of ADHD symptoms by at least 30% on the DSM-IV ADHD Behavior Checklist for Adults. Dextroamphetamine and modafinil showed the same response rate in 10 of 21 patients. Both treatments had a significant improvement over placebo (P<.001). It was unclear from the study what percentage of subjects responded to placebo.

A similar study compared dextroamphetamine, guanfacine (an antihypertensive agent), and placebo in 17 patients.⁵ On the DSM-IV ADHD Behavior Checklist for Adults, subjects taking dextroamphetamine or guanfacine reported similar decreases in mean ADHD scores compared with placebo (24 vs 22 vs 30; P<.05). They did not report the number of subjects who had a 30% reduction in symptoms. Of note: at the end of the study but prior to unblinding, subjects were asked which medication they preferred. Twelve subjects chose dextroamphetamine, 4 chose guanfacine, and 1 chose placebo. Subjects’ stated reason for choosing dextroamphetamine was the positive effect it had on their motivation.

Another study included in this review was a randomized controlled trial of mixed amphetamine salts. Of the 27 adults who completed the study, 19 (70%) responded favorably to mixed amphetamine salts compared with 2 (7.4%) receiving placebo (NNT=1.6; P<.001).⁶ Favorable response was defined as more than a 30% reduction of symptoms on the ADHD Rating Scale. Not included in either review was a 7-week randomized controlled trial comparing methylphenidate with sustained-release buproprion.⁷ Thirty out of 37 subjects completed at least 1 week of the study. The primary indicator of a favorable response was the Clinical Global Impression Scale. The rate of response was 50% for methylphenidate, 64% for sustained-release buproprion, and 27% for placebo (P<.14).

Recommendations from others

The American Academy of Child and Adolescent Psychiatry⁸ concluded that stimulant medication can be used to treat adults who have been carefully evaluated. They recommend starting methylphenidate, dextroamphetamine, or mixed amphetamine salts according to patient and clinician preference (Table). They do not recommend the use of pemoline due to the potential for hepatic failure.

TABLE
Stimulants used to treat ADHD in adults

Evidence summary

A well-done systematic review of 12 trials assessing the efficacy of stimulant therapy in the treatment of adult ADHD did not find sufficient evidence that stimulants were effective.¹ Significant heterogeneity and poor reporting of methodology was seen among the studies.

The 1 study rated as high-quality was a 7-week randomized controlled trial using a crossover comparison of methylphenidate and placebo.² There was a favorable response in 78% (18/23) of subjects while takin methylphenidate, in contrast to 4% (1/23) while taking placebo (number needed to treat [NNT]=1.4; P<.0001). A favorable response was assessed by the Clinical Global Impression Scale, a measure of illness severity and improvement, and a >30% reduction in symptoms as measured by the ADHD Rating Scale. A more recent, but less rigorous, systematic review identified 15 studies of stimulant efficacy in adults.³ Researchers concluded that under controlled conditions, stimulants are efficacious in the treatment of ADHD in adults. The rate of response among the studies ranged from 25% to 78%.

One of the better studies in this review was a randomized, double-blind, 3-phase crossover study of dextroamphetamine, modafinil (a drug used to treat narcolepsy), and placebo.⁴ Each phase was 2 weeks long, with a 4-day washout in between. A favorable response was defined as a reduction of ADHD symptoms by at least 30% on the DSM-IV ADHD Behavior Checklist for Adults. Dextroamphetamine and modafinil showed the same response rate in 10 of 21 patients. Both treatments had a significant improvement over placebo (P<.001). It was unclear from the study what percentage of subjects responded to placebo.

A similar study compared dextroamphetamine, guanfacine (an antihypertensive agent), and placebo in 17 patients.⁵ On the DSM-IV ADHD Behavior Checklist for Adults, subjects taking dextroamphetamine or guanfacine reported similar decreases in mean ADHD scores compared with placebo (24 vs 22 vs 30; P<.05). They did not report the number of subjects who had a 30% reduction in symptoms. Of note: at the end of the study but prior to unblinding, subjects were asked which medication they preferred. Twelve subjects chose dextroamphetamine, 4 chose guanfacine, and 1 chose placebo. Subjects’ stated reason for choosing dextroamphetamine was the positive effect it had on their motivation.

Another study included in this review was a randomized controlled trial of mixed amphetamine salts. Of the 27 adults who completed the study, 19 (70%) responded favorably to mixed amphetamine salts compared with 2 (7.4%) receiving placebo (NNT=1.6; P<.001).⁶ Favorable response was defined as more than a 30% reduction of symptoms on the ADHD Rating Scale. Not included in either review was a 7-week randomized controlled trial comparing methylphenidate with sustained-release buproprion.⁷ Thirty out of 37 subjects completed at least 1 week of the study. The primary indicator of a favorable response was the Clinical Global Impression Scale. The rate of response was 50% for methylphenidate, 64% for sustained-release buproprion, and 27% for placebo (P<.14).

Recommendations from others

The American Academy of Child and Adolescent Psychiatry⁸ concluded that stimulant medication can be used to treat adults who have been carefully evaluated. They recommend starting methylphenidate, dextroamphetamine, or mixed amphetamine salts according to patient and clinician preference (Table). They do not recommend the use of pemoline due to the potential for hepatic failure.

TABLE
Stimulants used to treat ADHD in adults

TABLE
Medications for Parkinson’s disease

Evidence summary

Five randomized controlled trials¹⁵ have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials^1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.⁶ A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.^7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.^11,12 There was no change in off-time with the combination.¹² A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.¹³

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.¹³ There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.^13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.¹⁵ Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.¹⁶ Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.^17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

• selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
• either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
• levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,²⁰ and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).

TABLE
Medications for Parkinson’s disease

Evidence summary

Five randomized controlled trials¹⁵ have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials^1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.⁶ A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.^7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.^11,12 There was no change in off-time with the combination.¹² A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.¹³

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.¹³ There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.^13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.¹⁵ Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.¹⁶ Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.^17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

• selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
• either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
• levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,²⁰ and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).

TABLE
Medications for Parkinson’s disease

Evidence summary

Five randomized controlled trials¹⁵ have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials^1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.⁶ A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.^7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.^11,12 There was no change in off-time with the combination.¹² A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.¹³

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.¹³ There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.^13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.¹⁵ Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.¹⁶ Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.^17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

• selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
• either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
• levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,²⁰ and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).

Evidence summary

The term “dietary fiber” refers to a heterogeneous group of substances that may vary in their biologic effects. Fiber is thought to reduce the risk of colon cancer through the following proposed mechanisms—decreased gastrointestinal transit time, increased stool bulk, and fermentation of volatile fatty acids. Other aspects of diet such as fat content, red meat, and micronutrients may also play a role in the development of colon cancer.

Additional proposed risk factors include sedentary lifestyle, obesity, tobacco use, and alcohol consumption¹ ; while the commonly accepted high-risk groups for colon cancer are those aged >60 years, those with a positive family history of colorectal cancer, and those with familial polyposis syndrome. In summary, it appears that the cause of colon cancer is complex and multifactorial.

No randomized controlled trials of interventions test whether increase dietary fiber affects the development of colon cancer. Recent randomized controlled trials of interventions have used colon polyps as a surrogate endpoint, since it is believed that polyps are precursors to cancer. A Cochrane meta-analysis² of 5 trials (including 4349 subjects) of increased dietary fiber to prevent recurrence of colon adenomas found no difference between intervention and control groups for development of at least 1 adenoma (relative risk [RR]=1.04; 95% confidence interval [CI], 0.95–1.13). In a trial³ of ispaghula husk fiber, the intervention group actually had significantly more recurrent adenomas after 3 years (29.3% vs 20.2%; RR=1.67; 95% CI, 1.01–2.76; P=.04).

Other evidence comes from epidemiological studies, which have limited ability to demonstrate causation. Immigrants to Westernized countries from ethnic groups with lower risk of colon cancer develop colon cancer rates similar to the host country over time. Such data support environmental factors in the risk for colon cancer.

Dietary fiber is 1 of several possible factors, yet epidemiological evidence has not been consistent. A systematic review⁴ of dietary fiber and colorectal neoplasia (which included case-control and cohort studies as well as randomized controlled trials) showed that 13 of 24 case-control studies found an association with high dietary fiber as a possible protective factor, while only 3 of 13 longitudinal studies found such an association.

Recommendations from others

The American Gastroenterological Association states that “currently available evidence from epidemiological, animal, and intervention studies does not unequivocally support the protective role of fiber against development of colorectal cancer.”⁵ They recommend dietary fiber consumption of at least 30–35 g/d from a variety of sources. The intake level of most studies that demonstrate protective effects are in that range, and it is not certain what the best source(s) may be. They state that a high-fiber diet should begin before age 30, because the impact of dietary change may require decades; they also note that a high-fiber diet has other established health benefits.

The American Dietetic Association recommends a diet rich in dietary fiber through consumption of a variety of fruits, vegetables, whole and high-fiber grain products, and legumes for a daily intake of 20–35 g/d for healthy adults and, for children, a daily intake of 5 plus the child’s age in grams.⁶ They cite the epidemiological association of a high-fiber diet and lower colorectal cancer risk as well as many other health benefits.

Evidence summary

The term “dietary fiber” refers to a heterogeneous group of substances that may vary in their biologic effects. Fiber is thought to reduce the risk of colon cancer through the following proposed mechanisms—decreased gastrointestinal transit time, increased stool bulk, and fermentation of volatile fatty acids. Other aspects of diet such as fat content, red meat, and micronutrients may also play a role in the development of colon cancer.

Additional proposed risk factors include sedentary lifestyle, obesity, tobacco use, and alcohol consumption¹ ; while the commonly accepted high-risk groups for colon cancer are those aged >60 years, those with a positive family history of colorectal cancer, and those with familial polyposis syndrome. In summary, it appears that the cause of colon cancer is complex and multifactorial.

No randomized controlled trials of interventions test whether increase dietary fiber affects the development of colon cancer. Recent randomized controlled trials of interventions have used colon polyps as a surrogate endpoint, since it is believed that polyps are precursors to cancer. A Cochrane meta-analysis² of 5 trials (including 4349 subjects) of increased dietary fiber to prevent recurrence of colon adenomas found no difference between intervention and control groups for development of at least 1 adenoma (relative risk [RR]=1.04; 95% confidence interval [CI], 0.95–1.13). In a trial³ of ispaghula husk fiber, the intervention group actually had significantly more recurrent adenomas after 3 years (29.3% vs 20.2%; RR=1.67; 95% CI, 1.01–2.76; P=.04).

Other evidence comes from epidemiological studies, which have limited ability to demonstrate causation. Immigrants to Westernized countries from ethnic groups with lower risk of colon cancer develop colon cancer rates similar to the host country over time. Such data support environmental factors in the risk for colon cancer.

Dietary fiber is 1 of several possible factors, yet epidemiological evidence has not been consistent. A systematic review⁴ of dietary fiber and colorectal neoplasia (which included case-control and cohort studies as well as randomized controlled trials) showed that 13 of 24 case-control studies found an association with high dietary fiber as a possible protective factor, while only 3 of 13 longitudinal studies found such an association.

Recommendations from others

The American Gastroenterological Association states that “currently available evidence from epidemiological, animal, and intervention studies does not unequivocally support the protective role of fiber against development of colorectal cancer.”⁵ They recommend dietary fiber consumption of at least 30–35 g/d from a variety of sources. The intake level of most studies that demonstrate protective effects are in that range, and it is not certain what the best source(s) may be. They state that a high-fiber diet should begin before age 30, because the impact of dietary change may require decades; they also note that a high-fiber diet has other established health benefits.

The American Dietetic Association recommends a diet rich in dietary fiber through consumption of a variety of fruits, vegetables, whole and high-fiber grain products, and legumes for a daily intake of 20–35 g/d for healthy adults and, for children, a daily intake of 5 plus the child’s age in grams.⁶ They cite the epidemiological association of a high-fiber diet and lower colorectal cancer risk as well as many other health benefits.

Evidence summary

The term “dietary fiber” refers to a heterogeneous group of substances that may vary in their biologic effects. Fiber is thought to reduce the risk of colon cancer through the following proposed mechanisms—decreased gastrointestinal transit time, increased stool bulk, and fermentation of volatile fatty acids. Other aspects of diet such as fat content, red meat, and micronutrients may also play a role in the development of colon cancer.

Additional proposed risk factors include sedentary lifestyle, obesity, tobacco use, and alcohol consumption¹ ; while the commonly accepted high-risk groups for colon cancer are those aged >60 years, those with a positive family history of colorectal cancer, and those with familial polyposis syndrome. In summary, it appears that the cause of colon cancer is complex and multifactorial.

No randomized controlled trials of interventions test whether increase dietary fiber affects the development of colon cancer. Recent randomized controlled trials of interventions have used colon polyps as a surrogate endpoint, since it is believed that polyps are precursors to cancer. A Cochrane meta-analysis² of 5 trials (including 4349 subjects) of increased dietary fiber to prevent recurrence of colon adenomas found no difference between intervention and control groups for development of at least 1 adenoma (relative risk [RR]=1.04; 95% confidence interval [CI], 0.95–1.13). In a trial³ of ispaghula husk fiber, the intervention group actually had significantly more recurrent adenomas after 3 years (29.3% vs 20.2%; RR=1.67; 95% CI, 1.01–2.76; P=.04).

Other evidence comes from epidemiological studies, which have limited ability to demonstrate causation. Immigrants to Westernized countries from ethnic groups with lower risk of colon cancer develop colon cancer rates similar to the host country over time. Such data support environmental factors in the risk for colon cancer.

Dietary fiber is 1 of several possible factors, yet epidemiological evidence has not been consistent. A systematic review⁴ of dietary fiber and colorectal neoplasia (which included case-control and cohort studies as well as randomized controlled trials) showed that 13 of 24 case-control studies found an association with high dietary fiber as a possible protective factor, while only 3 of 13 longitudinal studies found such an association.

Recommendations from others

The American Gastroenterological Association states that “currently available evidence from epidemiological, animal, and intervention studies does not unequivocally support the protective role of fiber against development of colorectal cancer.”⁵ They recommend dietary fiber consumption of at least 30–35 g/d from a variety of sources. The intake level of most studies that demonstrate protective effects are in that range, and it is not certain what the best source(s) may be. They state that a high-fiber diet should begin before age 30, because the impact of dietary change may require decades; they also note that a high-fiber diet has other established health benefits.

The American Dietetic Association recommends a diet rich in dietary fiber through consumption of a variety of fruits, vegetables, whole and high-fiber grain products, and legumes for a daily intake of 20–35 g/d for healthy adults and, for children, a daily intake of 5 plus the child’s age in grams.⁶ They cite the epidemiological association of a high-fiber diet and lower colorectal cancer risk as well as many other health benefits.

Evidence summary

Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developed^2-4 and developing^1,5 countries. Many cases of gastroenteritis without a confirmed enteropathogen have viral causes. Rotavirus is a common viral pathogen in children aged <2 years, and much of the evidence about breastfeeding and viral gastroenteritis comes from studies about rotavirus infections.

Prospective cohort studies conducted in Canada⁶ and the United States⁷ showed no difference in the incidence of rotavirus gastroenteritis between infants up to 2 years of age who were breastfed and those who were not. Although differences were not found between either the incidence or the duration of rotavirus infections, these studies showed a significant decrease in the frequency of vomiting among breastfed infants.

A case-control study in Bangladesh suggests that breastfed infants have a higher incidence of rotavirus diarrhea, but selection of diarrhea patients as controls may have underestimated the protective effect.⁸ Although breastfeeding was not found to provide overall protection from developing rotavirus gastroenteritis, exclusive breastfeeding appeared to protect against severe rotavirus diarrhea for infants aged <2 years.

Another US study showed that risk for rotavirus infection did not differ for infants who were exclusively breastfed, partially breastfed, or exclusively formula-fed.¹⁰ However, the breastfed infants were more likely to have milder symptoms.

RECOMMENDATIONS FROM OTHERS

The American Academy of Family Physicians¹¹ and the American Academy of Pediatrics¹² recommend exclusive breastfeeding for a minimum of the first 6 months of life, and continuation of breastfeeding to supplement age-appropriate foods through the next 6 months. The World Health Organization¹³ recommends exclusive breastfeeding for the first 4 to 6 months of life, and continuation of breastfeeding for 2 years of age or beyond.

Evidence summary

Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developed^2-4 and developing^1,5 countries. Many cases of gastroenteritis without a confirmed enteropathogen have viral causes. Rotavirus is a common viral pathogen in children aged <2 years, and much of the evidence about breastfeeding and viral gastroenteritis comes from studies about rotavirus infections.

Prospective cohort studies conducted in Canada⁶ and the United States⁷ showed no difference in the incidence of rotavirus gastroenteritis between infants up to 2 years of age who were breastfed and those who were not. Although differences were not found between either the incidence or the duration of rotavirus infections, these studies showed a significant decrease in the frequency of vomiting among breastfed infants.

A case-control study in Bangladesh suggests that breastfed infants have a higher incidence of rotavirus diarrhea, but selection of diarrhea patients as controls may have underestimated the protective effect.⁸ Although breastfeeding was not found to provide overall protection from developing rotavirus gastroenteritis, exclusive breastfeeding appeared to protect against severe rotavirus diarrhea for infants aged <2 years.

Another US study showed that risk for rotavirus infection did not differ for infants who were exclusively breastfed, partially breastfed, or exclusively formula-fed.¹⁰ However, the breastfed infants were more likely to have milder symptoms.

RECOMMENDATIONS FROM OTHERS

The American Academy of Family Physicians¹¹ and the American Academy of Pediatrics¹² recommend exclusive breastfeeding for a minimum of the first 6 months of life, and continuation of breastfeeding to supplement age-appropriate foods through the next 6 months. The World Health Organization¹³ recommends exclusive breastfeeding for the first 4 to 6 months of life, and continuation of breastfeeding for 2 years of age or beyond.

Evidence summary

Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developed^2-4 and developing^1,5 countries. Many cases of gastroenteritis without a confirmed enteropathogen have viral causes. Rotavirus is a common viral pathogen in children aged <2 years, and much of the evidence about breastfeeding and viral gastroenteritis comes from studies about rotavirus infections.

Prospective cohort studies conducted in Canada⁶ and the United States⁷ showed no difference in the incidence of rotavirus gastroenteritis between infants up to 2 years of age who were breastfed and those who were not. Although differences were not found between either the incidence or the duration of rotavirus infections, these studies showed a significant decrease in the frequency of vomiting among breastfed infants.

A case-control study in Bangladesh suggests that breastfed infants have a higher incidence of rotavirus diarrhea, but selection of diarrhea patients as controls may have underestimated the protective effect.⁸ Although breastfeeding was not found to provide overall protection from developing rotavirus gastroenteritis, exclusive breastfeeding appeared to protect against severe rotavirus diarrhea for infants aged <2 years.

Another US study showed that risk for rotavirus infection did not differ for infants who were exclusively breastfed, partially breastfed, or exclusively formula-fed.¹⁰ However, the breastfed infants were more likely to have milder symptoms.

RECOMMENDATIONS FROM OTHERS

The American Academy of Family Physicians¹¹ and the American Academy of Pediatrics¹² recommend exclusive breastfeeding for a minimum of the first 6 months of life, and continuation of breastfeeding to supplement age-appropriate foods through the next 6 months. The World Health Organization¹³ recommends exclusive breastfeeding for the first 4 to 6 months of life, and continuation of breastfeeding for 2 years of age or beyond.

Evidence summary

Amitryptyline was moderately efficacious in 3 small nonblinded trials.^1,2 The largest and best-designed prospective cohort trial studied 192 children. Of the 146 patients available for the first follow-up visit, 84% noted subjective improvement of symptoms. Headache frequency decreased from 17.1 ± 10.1 to 9.2 ± 10.0 days/month (P<.001).¹

Propranolol, although widely used in children, has conflicting evidence regarding effectiveness. One small randomized controlled trial showed reduced headache frequency in children when compared with placebo.³ However, these results were not duplicated in a larger randomized controlled trial using slightly smaller doses.⁴

A comparative randomized controlled trial with multiple crossovers involving 33 children found that a self-hypnosis placebo decreased mean headache frequency from 13.3 per 3-month interval to 5.8 (P=.045), but found propranolol no different than placebo.⁵ Propranolol was also studied in a 3-armed randomized controlled trial in comparison with flunarizine—a drug likely to be efficacious—and placebo. Both drugs were equally efficacious and superior to placebo according to reviews; however, these results were not published in English and could not be critiqued by this author.²

In 2 small retrospective case studies, valproic acid demonstrated >50% improvement in symptoms in 65%⁶ and 78%⁷ of subjects. A single uncontrolled interventional trial of valproic acid in 10 children showed a significant trend of improvement in frequency (mean of 6 attacks/month to 0.8 attacks/month) and duration (mean 5.5 hours per attack to 1.1 hour).⁸

Two similar vasodilatory calcium channel blockers, flunarizine and nimodipine, have the best evidence as migraine prophylactics in children. Flunarizine was found to be effective in multiple well-designed randomized controlled trials and case series, as well as in multiple comparative trials with other agents.²

In a double-blinded, placebo-controlled randomized controlled trial of 48 children, flunarizine decreased mean headache frequency (3.0 attacks/3 months vs 6.5 [P<.001]).⁹ A repeat randomized controlled trial in 70 children had similar outcomes.¹⁰

Nimodipine, in a single randomized controlled trial with crossover design in 37 children decreased headache frequency from a mean of ~2.7 attacks/month to ~1.9 vs. no change for placebo (P<.05).¹¹ A small, prospective, nonblinded comparative trial found that nimodipine and flunarizine have similar efficacy and are superior to placebo.¹²

Cyproheptadine is widely used in children but is not as effective as amitriptyline and propranolol.² In adults it is not considered a first-line agent due to lack of evidence of efficacy.¹³ Nonsteroidal anti-inflammatory drugs have insufficient data to recommend them as prophylactic medications in children.²

RECOMMENDATIONS FROM OTHERS

Nelson Textbook of Pediatrics recommends propranolol as a first-line agent for prevention.¹⁴

A recent review article15 recommends cyproheptadine as an initial agent in children <10 years of age. This article also has a patient handout discussing nonpharmacologic prophylactics such as regular sleep, exercise, stress reduction, and avoiding certain foods.

UpToDate recommends propranolol, cyproheptadine, valproate, and amitriptyline as prophylactic options based on patient parameters such as age, sex, and comorbid conditions.¹⁶

Evidence summary

Amitryptyline was moderately efficacious in 3 small nonblinded trials.^1,2 The largest and best-designed prospective cohort trial studied 192 children. Of the 146 patients available for the first follow-up visit, 84% noted subjective improvement of symptoms. Headache frequency decreased from 17.1 ± 10.1 to 9.2 ± 10.0 days/month (P<.001).¹

Propranolol, although widely used in children, has conflicting evidence regarding effectiveness. One small randomized controlled trial showed reduced headache frequency in children when compared with placebo.³ However, these results were not duplicated in a larger randomized controlled trial using slightly smaller doses.⁴

A comparative randomized controlled trial with multiple crossovers involving 33 children found that a self-hypnosis placebo decreased mean headache frequency from 13.3 per 3-month interval to 5.8 (P=.045), but found propranolol no different than placebo.⁵ Propranolol was also studied in a 3-armed randomized controlled trial in comparison with flunarizine—a drug likely to be efficacious—and placebo. Both drugs were equally efficacious and superior to placebo according to reviews; however, these results were not published in English and could not be critiqued by this author.²

In 2 small retrospective case studies, valproic acid demonstrated >50% improvement in symptoms in 65%⁶ and 78%⁷ of subjects. A single uncontrolled interventional trial of valproic acid in 10 children showed a significant trend of improvement in frequency (mean of 6 attacks/month to 0.8 attacks/month) and duration (mean 5.5 hours per attack to 1.1 hour).⁸

Two similar vasodilatory calcium channel blockers, flunarizine and nimodipine, have the best evidence as migraine prophylactics in children. Flunarizine was found to be effective in multiple well-designed randomized controlled trials and case series, as well as in multiple comparative trials with other agents.²

In a double-blinded, placebo-controlled randomized controlled trial of 48 children, flunarizine decreased mean headache frequency (3.0 attacks/3 months vs 6.5 [P<.001]).⁹ A repeat randomized controlled trial in 70 children had similar outcomes.¹⁰

Nimodipine, in a single randomized controlled trial with crossover design in 37 children decreased headache frequency from a mean of ~2.7 attacks/month to ~1.9 vs. no change for placebo (P<.05).¹¹ A small, prospective, nonblinded comparative trial found that nimodipine and flunarizine have similar efficacy and are superior to placebo.¹²

Cyproheptadine is widely used in children but is not as effective as amitriptyline and propranolol.² In adults it is not considered a first-line agent due to lack of evidence of efficacy.¹³ Nonsteroidal anti-inflammatory drugs have insufficient data to recommend them as prophylactic medications in children.²

RECOMMENDATIONS FROM OTHERS

Nelson Textbook of Pediatrics recommends propranolol as a first-line agent for prevention.¹⁴

A recent review article15 recommends cyproheptadine as an initial agent in children <10 years of age. This article also has a patient handout discussing nonpharmacologic prophylactics such as regular sleep, exercise, stress reduction, and avoiding certain foods.

UpToDate recommends propranolol, cyproheptadine, valproate, and amitriptyline as prophylactic options based on patient parameters such as age, sex, and comorbid conditions.¹⁶

Evidence summary

Amitryptyline was moderately efficacious in 3 small nonblinded trials.^1,2 The largest and best-designed prospective cohort trial studied 192 children. Of the 146 patients available for the first follow-up visit, 84% noted subjective improvement of symptoms. Headache frequency decreased from 17.1 ± 10.1 to 9.2 ± 10.0 days/month (P<.001).¹

Propranolol, although widely used in children, has conflicting evidence regarding effectiveness. One small randomized controlled trial showed reduced headache frequency in children when compared with placebo.³ However, these results were not duplicated in a larger randomized controlled trial using slightly smaller doses.⁴

A comparative randomized controlled trial with multiple crossovers involving 33 children found that a self-hypnosis placebo decreased mean headache frequency from 13.3 per 3-month interval to 5.8 (P=.045), but found propranolol no different than placebo.⁵ Propranolol was also studied in a 3-armed randomized controlled trial in comparison with flunarizine—a drug likely to be efficacious—and placebo. Both drugs were equally efficacious and superior to placebo according to reviews; however, these results were not published in English and could not be critiqued by this author.²

In 2 small retrospective case studies, valproic acid demonstrated >50% improvement in symptoms in 65%⁶ and 78%⁷ of subjects. A single uncontrolled interventional trial of valproic acid in 10 children showed a significant trend of improvement in frequency (mean of 6 attacks/month to 0.8 attacks/month) and duration (mean 5.5 hours per attack to 1.1 hour).⁸

Two similar vasodilatory calcium channel blockers, flunarizine and nimodipine, have the best evidence as migraine prophylactics in children. Flunarizine was found to be effective in multiple well-designed randomized controlled trials and case series, as well as in multiple comparative trials with other agents.²

In a double-blinded, placebo-controlled randomized controlled trial of 48 children, flunarizine decreased mean headache frequency (3.0 attacks/3 months vs 6.5 [P<.001]).⁹ A repeat randomized controlled trial in 70 children had similar outcomes.¹⁰

Nimodipine, in a single randomized controlled trial with crossover design in 37 children decreased headache frequency from a mean of ~2.7 attacks/month to ~1.9 vs. no change for placebo (P<.05).¹¹ A small, prospective, nonblinded comparative trial found that nimodipine and flunarizine have similar efficacy and are superior to placebo.¹²

Cyproheptadine is widely used in children but is not as effective as amitriptyline and propranolol.² In adults it is not considered a first-line agent due to lack of evidence of efficacy.¹³ Nonsteroidal anti-inflammatory drugs have insufficient data to recommend them as prophylactic medications in children.²

RECOMMENDATIONS FROM OTHERS

Nelson Textbook of Pediatrics recommends propranolol as a first-line agent for prevention.¹⁴

A recent review article15 recommends cyproheptadine as an initial agent in children <10 years of age. This article also has a patient handout discussing nonpharmacologic prophylactics such as regular sleep, exercise, stress reduction, and avoiding certain foods.

UpToDate recommends propranolol, cyproheptadine, valproate, and amitriptyline as prophylactic options based on patient parameters such as age, sex, and comorbid conditions.¹⁶

Evidence summary

Standardized clinical criteria (Table) exist to determine the risk of serious bacterial infection, which includes meningitis; of particular note, these criteria do not require cerebrospinal fluid examination. Infants aged <3 months who fall into the “high-risk” category or appear toxic have 21% probability of a serious bacterial infection, 10% probability of bacteremia, and 2% probability of bacterial meningitis.¹ The “low-risk” infants have a correspondingly lower incidence of serious bacterial infection: the negative predictive value of the Rochester classification is 98.9% (95% confidence interval [CI], 97.2–99.6%).²

The negative predictive value for bacterial meningitis (a subset of serious bacterial infection) is even greater. Five studies applied the standardized criteria to febrile infants and monitored them for the development of serious bacterial infection, including meningitis. Two prospective cohort studies of outpatients aged 0 to 2 months used the Rochester criteria to assign infants to risk groups. They studied a total of 1294 infants; 659 (51%) were low-risk. None of the low-risk infants developed bacterial meningitis.^2,3

One prospective cohort study of infants aged <1 month hospitalized for fever used a similar method for assessing risk, but added a C-reactive protein value <20 mg/L to criteria for low-risk. Of 250 infants studied, 131 (52%) were low-risk; none of these developed bacterial meningitis.⁴

A retrospective chart review of 492 infants aged <3 months who were hospitalized due to fever included 108 infants aged <1 month. Thirty percent (114) of the infants aged 1 to 3 months and 67% (72) of the younger infants underwent lumbar puncture at the discretion of the treating physician. All infants were retrospectively assigned to low- or high-risk groups for serious bacterial infection using the Rochester criteria. Of the 296 infants rated “low-risk,” none developed bacterial meningitis. Ten of these infants subsequently developed evidence of another bacterial focus (predominantly urinary tract infection).⁵

RECOMMENDATIONS FROM OTHERS

The American Academy of Pediatrics has not issued a clinical practice guideline or clinical report addressing this issue. An evidence-based guideline developed at Cincinnati Children’s Hospital Medical Center in 1998 recommends hospitalization and a full sepsis workup (including lumbar puncture) for infants aged <1 month, or infants aged 1 to 2 months who are high-risk.⁶

A clinical review-based guideline published in 1993 gives the same recommendations.⁷ The expert panel that devised this guideline emphasized a full sepsis evaluation (including cerebrospinal fluid cultures) for infants <28 days of age “despite the low probability of serious bacterial infections in this age group and the favorable outcome of the children managed to date with careful observation.” For low-risk infants aged 1 to 2 months, lumbar puncture is not necessary unless empiric antibiotics are given; having a cerebrospinal fluid culture prior to empiric antibiotics reduces the concern of partially treated meningitis in the case of clinical deterioration after hospital discharge.^6,7

TABLE
How to identify infants at low risk of serious bacterial infection: Rochester Classification

Evidence summary

Standardized clinical criteria (Table) exist to determine the risk of serious bacterial infection, which includes meningitis; of particular note, these criteria do not require cerebrospinal fluid examination. Infants aged <3 months who fall into the “high-risk” category or appear toxic have 21% probability of a serious bacterial infection, 10% probability of bacteremia, and 2% probability of bacterial meningitis.¹ The “low-risk” infants have a correspondingly lower incidence of serious bacterial infection: the negative predictive value of the Rochester classification is 98.9% (95% confidence interval [CI], 97.2–99.6%).²

The negative predictive value for bacterial meningitis (a subset of serious bacterial infection) is even greater. Five studies applied the standardized criteria to febrile infants and monitored them for the development of serious bacterial infection, including meningitis. Two prospective cohort studies of outpatients aged 0 to 2 months used the Rochester criteria to assign infants to risk groups. They studied a total of 1294 infants; 659 (51%) were low-risk. None of the low-risk infants developed bacterial meningitis.^2,3

One prospective cohort study of infants aged <1 month hospitalized for fever used a similar method for assessing risk, but added a C-reactive protein value <20 mg/L to criteria for low-risk. Of 250 infants studied, 131 (52%) were low-risk; none of these developed bacterial meningitis.⁴

A retrospective chart review of 492 infants aged <3 months who were hospitalized due to fever included 108 infants aged <1 month. Thirty percent (114) of the infants aged 1 to 3 months and 67% (72) of the younger infants underwent lumbar puncture at the discretion of the treating physician. All infants were retrospectively assigned to low- or high-risk groups for serious bacterial infection using the Rochester criteria. Of the 296 infants rated “low-risk,” none developed bacterial meningitis. Ten of these infants subsequently developed evidence of another bacterial focus (predominantly urinary tract infection).⁵

RECOMMENDATIONS FROM OTHERS

The American Academy of Pediatrics has not issued a clinical practice guideline or clinical report addressing this issue. An evidence-based guideline developed at Cincinnati Children’s Hospital Medical Center in 1998 recommends hospitalization and a full sepsis workup (including lumbar puncture) for infants aged <1 month, or infants aged 1 to 2 months who are high-risk.⁶

A clinical review-based guideline published in 1993 gives the same recommendations.⁷ The expert panel that devised this guideline emphasized a full sepsis evaluation (including cerebrospinal fluid cultures) for infants <28 days of age “despite the low probability of serious bacterial infections in this age group and the favorable outcome of the children managed to date with careful observation.” For low-risk infants aged 1 to 2 months, lumbar puncture is not necessary unless empiric antibiotics are given; having a cerebrospinal fluid culture prior to empiric antibiotics reduces the concern of partially treated meningitis in the case of clinical deterioration after hospital discharge.^6,7

TABLE
How to identify infants at low risk of serious bacterial infection: Rochester Classification

Evidence summary

Standardized clinical criteria (Table) exist to determine the risk of serious bacterial infection, which includes meningitis; of particular note, these criteria do not require cerebrospinal fluid examination. Infants aged <3 months who fall into the “high-risk” category or appear toxic have 21% probability of a serious bacterial infection, 10% probability of bacteremia, and 2% probability of bacterial meningitis.¹ The “low-risk” infants have a correspondingly lower incidence of serious bacterial infection: the negative predictive value of the Rochester classification is 98.9% (95% confidence interval [CI], 97.2–99.6%).²

The negative predictive value for bacterial meningitis (a subset of serious bacterial infection) is even greater. Five studies applied the standardized criteria to febrile infants and monitored them for the development of serious bacterial infection, including meningitis. Two prospective cohort studies of outpatients aged 0 to 2 months used the Rochester criteria to assign infants to risk groups. They studied a total of 1294 infants; 659 (51%) were low-risk. None of the low-risk infants developed bacterial meningitis.^2,3

One prospective cohort study of infants aged <1 month hospitalized for fever used a similar method for assessing risk, but added a C-reactive protein value <20 mg/L to criteria for low-risk. Of 250 infants studied, 131 (52%) were low-risk; none of these developed bacterial meningitis.⁴

A retrospective chart review of 492 infants aged <3 months who were hospitalized due to fever included 108 infants aged <1 month. Thirty percent (114) of the infants aged 1 to 3 months and 67% (72) of the younger infants underwent lumbar puncture at the discretion of the treating physician. All infants were retrospectively assigned to low- or high-risk groups for serious bacterial infection using the Rochester criteria. Of the 296 infants rated “low-risk,” none developed bacterial meningitis. Ten of these infants subsequently developed evidence of another bacterial focus (predominantly urinary tract infection).⁵

RECOMMENDATIONS FROM OTHERS

The American Academy of Pediatrics has not issued a clinical practice guideline or clinical report addressing this issue. An evidence-based guideline developed at Cincinnati Children’s Hospital Medical Center in 1998 recommends hospitalization and a full sepsis workup (including lumbar puncture) for infants aged <1 month, or infants aged 1 to 2 months who are high-risk.⁶

A clinical review-based guideline published in 1993 gives the same recommendations.⁷ The expert panel that devised this guideline emphasized a full sepsis evaluation (including cerebrospinal fluid cultures) for infants <28 days of age “despite the low probability of serious bacterial infections in this age group and the favorable outcome of the children managed to date with careful observation.” For low-risk infants aged 1 to 2 months, lumbar puncture is not necessary unless empiric antibiotics are given; having a cerebrospinal fluid culture prior to empiric antibiotics reduces the concern of partially treated meningitis in the case of clinical deterioration after hospital discharge.^6,7

TABLE
How to identify infants at low risk of serious bacterial infection: Rochester Classification

Evidence summary

Functional braces are designed to provide stability for the unstable knee, but few trials report re-injury rates as an outcome. Cadaver studies show that braces limit tibial rotation and anteroposterior translation. However, the mechanical effects of knee bracing in vivo are controversial.

A study involving 5 patients with chronic unstable ACL injuries showed some limitation of movement with functional bracing, but it was accompanied by slowed muscle performance and used only low-stress forces.¹ Objective findings during physiologic stress loads are inconclusive.²

Three recent randomized controlled trials compared functional bracing with no bracing in rehabilitation after ACL reconstruction. In a prospective study of 62 patients, researchers found no benefit from using a postoperative knee brace at any stage (2 and 6 weeks; 3, 6, and 24 months) after surgery. Moreover, the brace did not contribute to a more stable knee during rehabilitation or 2-year follow-up.³

A similar study of 50 patients demonstrated no significant difference in function or laxity at 2 years.⁴ A 2-year study comparing 30 braced with 30 nonbraced patients showed improved functional stability (P<.05) but increased thigh muscle atrophy (P<.0001) at 3-month follow-up in the braced group. However, no significant differences were seen at other follow-up intervals up to 2 years.⁵

One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace.⁶

RECOMMENDATIONS FROM OTHERS

The American Association of Orthopaedic Surgeons believes that rehabilitative and functional knee braces can be effective in many treatment programs. Rehabilitative braces are more effective in protecting against excessive flexion and extension than against anterior and posterior motion. Functional braces reduce abnormal movement under low load conditions but do not restore normal knee stability under high forces related to certain athletic activities. Physician and patient must guard against a false sense of security.⁷

The American Academy of Pediatrics says that functional braces may help prevent further injury to a previously injured knee. Their use is accepted clinically on the basis of subjective performance. If used, knee braces should complement rehabilitative therapy and required surgery.⁸

Evidence summary

Functional braces are designed to provide stability for the unstable knee, but few trials report re-injury rates as an outcome. Cadaver studies show that braces limit tibial rotation and anteroposterior translation. However, the mechanical effects of knee bracing in vivo are controversial.

A study involving 5 patients with chronic unstable ACL injuries showed some limitation of movement with functional bracing, but it was accompanied by slowed muscle performance and used only low-stress forces.¹ Objective findings during physiologic stress loads are inconclusive.²

Three recent randomized controlled trials compared functional bracing with no bracing in rehabilitation after ACL reconstruction. In a prospective study of 62 patients, researchers found no benefit from using a postoperative knee brace at any stage (2 and 6 weeks; 3, 6, and 24 months) after surgery. Moreover, the brace did not contribute to a more stable knee during rehabilitation or 2-year follow-up.³

A similar study of 50 patients demonstrated no significant difference in function or laxity at 2 years.⁴ A 2-year study comparing 30 braced with 30 nonbraced patients showed improved functional stability (P<.05) but increased thigh muscle atrophy (P<.0001) at 3-month follow-up in the braced group. However, no significant differences were seen at other follow-up intervals up to 2 years.⁵

One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace.⁶

RECOMMENDATIONS FROM OTHERS

The American Association of Orthopaedic Surgeons believes that rehabilitative and functional knee braces can be effective in many treatment programs. Rehabilitative braces are more effective in protecting against excessive flexion and extension than against anterior and posterior motion. Functional braces reduce abnormal movement under low load conditions but do not restore normal knee stability under high forces related to certain athletic activities. Physician and patient must guard against a false sense of security.⁷

The American Academy of Pediatrics says that functional braces may help prevent further injury to a previously injured knee. Their use is accepted clinically on the basis of subjective performance. If used, knee braces should complement rehabilitative therapy and required surgery.⁸

Evidence summary

Functional braces are designed to provide stability for the unstable knee, but few trials report re-injury rates as an outcome. Cadaver studies show that braces limit tibial rotation and anteroposterior translation. However, the mechanical effects of knee bracing in vivo are controversial.

A study involving 5 patients with chronic unstable ACL injuries showed some limitation of movement with functional bracing, but it was accompanied by slowed muscle performance and used only low-stress forces.¹ Objective findings during physiologic stress loads are inconclusive.²

Three recent randomized controlled trials compared functional bracing with no bracing in rehabilitation after ACL reconstruction. In a prospective study of 62 patients, researchers found no benefit from using a postoperative knee brace at any stage (2 and 6 weeks; 3, 6, and 24 months) after surgery. Moreover, the brace did not contribute to a more stable knee during rehabilitation or 2-year follow-up.³

A similar study of 50 patients demonstrated no significant difference in function or laxity at 2 years.⁴ A 2-year study comparing 30 braced with 30 nonbraced patients showed improved functional stability (P<.05) but increased thigh muscle atrophy (P<.0001) at 3-month follow-up in the braced group. However, no significant differences were seen at other follow-up intervals up to 2 years.⁵

One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace.⁶

RECOMMENDATIONS FROM OTHERS

The American Association of Orthopaedic Surgeons believes that rehabilitative and functional knee braces can be effective in many treatment programs. Rehabilitative braces are more effective in protecting against excessive flexion and extension than against anterior and posterior motion. Functional braces reduce abnormal movement under low load conditions but do not restore normal knee stability under high forces related to certain athletic activities. Physician and patient must guard against a false sense of security.⁷

The American Academy of Pediatrics says that functional braces may help prevent further injury to a previously injured knee. Their use is accepted clinically on the basis of subjective performance. If used, knee braces should complement rehabilitative therapy and required surgery.⁸