Doug Brunk

The Food and Drug Administration has sent letters to all manufacturers of medications approved for treating attention-deficit hyperactivity disorder, instructing them to develop patient medication guides within 30 days to address possible cardiovascular risks and adverse psychiatric symptoms associated with their use.

The ruling builds on regulatory action the FDA took last May when it directed manufacturers to revise product labeling for physicians to reflect concerns about adverse cardiovascular and psychiatric events. The concerns came from an FDA review of reports of sudden unexplained death in patients taking usual doses of ADHD products, said Dr. Tom Laughren, director of the division of psychiatry products at the FDA Center for Drug Evaluation and Research, during a teleconference.

Concern about adverse psychiatric events, principally psychotic symptoms, comes from another FDA review, including spontaneous reports and pooled analyses of placebo-controlled trials.

“The causal link is stronger for this event than it is for cardiovascular events,” Dr. Laughren said, noting that adverse psychiatric events occur in about 1 of every 1,000 patients treated.

The ruling applies to 15 products: Adderall tablets, Adderall XR extended-release capsules, Concerta extended-release tablets, Daytrana transdermal system, Desoxyn tablets, Dexedrine Spansule capsules and tablets, Focalin tablets, Focalin XR extended-release capsules, Metadate CD extended-release capsules, Methylin oral solution, Methylin chewable tablets, Ritalin tablets, Ritalin SR sustained-release tablets, Ritalin LA extended-release capsules, and Strattera capsules.

Draft medication guides for these products can be found at www.fda.gov/cder/drug/infopage/ADHD/default.htm

The Food and Drug Administration has sent letters to all manufacturers of medications approved for treating attention-deficit hyperactivity disorder, instructing them to develop patient medication guides within 30 days to address possible cardiovascular risks and adverse psychiatric symptoms associated with their use.

The ruling builds on regulatory action the FDA took last May when it directed manufacturers to revise product labeling for physicians to reflect concerns about adverse cardiovascular and psychiatric events. The concerns came from an FDA review of reports of sudden unexplained death in patients taking usual doses of ADHD products, said Dr. Tom Laughren, director of the division of psychiatry products at the FDA Center for Drug Evaluation and Research, during a teleconference.

Concern about adverse psychiatric events, principally psychotic symptoms, comes from another FDA review, including spontaneous reports and pooled analyses of placebo-controlled trials.

“The causal link is stronger for this event than it is for cardiovascular events,” Dr. Laughren said, noting that adverse psychiatric events occur in about 1 of every 1,000 patients treated.

The ruling applies to 15 products: Adderall tablets, Adderall XR extended-release capsules, Concerta extended-release tablets, Daytrana transdermal system, Desoxyn tablets, Dexedrine Spansule capsules and tablets, Focalin tablets, Focalin XR extended-release capsules, Metadate CD extended-release capsules, Methylin oral solution, Methylin chewable tablets, Ritalin tablets, Ritalin SR sustained-release tablets, Ritalin LA extended-release capsules, and Strattera capsules.

Draft medication guides for these products can be found at www.fda.gov/cder/drug/infopage/ADHD/default.htm

The Food and Drug Administration has sent letters to all manufacturers of medications approved for treating attention-deficit hyperactivity disorder, instructing them to develop patient medication guides within 30 days to address possible cardiovascular risks and adverse psychiatric symptoms associated with their use.

The ruling builds on regulatory action the FDA took last May when it directed manufacturers to revise product labeling for physicians to reflect concerns about adverse cardiovascular and psychiatric events. The concerns came from an FDA review of reports of sudden unexplained death in patients taking usual doses of ADHD products, said Dr. Tom Laughren, director of the division of psychiatry products at the FDA Center for Drug Evaluation and Research, during a teleconference.

Concern about adverse psychiatric events, principally psychotic symptoms, comes from another FDA review, including spontaneous reports and pooled analyses of placebo-controlled trials.

“The causal link is stronger for this event than it is for cardiovascular events,” Dr. Laughren said, noting that adverse psychiatric events occur in about 1 of every 1,000 patients treated.

The ruling applies to 15 products: Adderall tablets, Adderall XR extended-release capsules, Concerta extended-release tablets, Daytrana transdermal system, Desoxyn tablets, Dexedrine Spansule capsules and tablets, Focalin tablets, Focalin XR extended-release capsules, Metadate CD extended-release capsules, Methylin oral solution, Methylin chewable tablets, Ritalin tablets, Ritalin SR sustained-release tablets, Ritalin LA extended-release capsules, and Strattera capsules.

Draft medication guides for these products can be found at www.fda.gov/cder/drug/infopage/ADHD/default.htm

CARMEL, CALIF. — Low baseline total serum testosterone levels could be a marker for obstructive sleep apnea in older men, Yao Schmidt reported at the Western regional meeting of the American Federation for Medical Research.

Of men aged 60–80 years, 20%–60% have borderline hypogonadism, said Ms. Schmidt, who is a second-year medical student at the University of Colorado Health Sciences Center, Denver.

She and associates evaluated 28 men aged 60–80 years. They recorded apnea-hypopnea index (AHI), baseline total serum testosterone level, age, body mass index (BMI), neck size, and LDL cholesterol level. Mean age was 67 years, mean BMI was 29 kg/m

Patients were divided into two groups: 14 with obstructive sleep apnea, defined as having an AHI of 10 or greater, and 14 men without.

Mean baseline serum testosterone level in the men with obstructive sleep apnea was 262 ng/dL, compared with a mean of 315 ng/dL in the men without, which was statistically significant. There were no significant differences between groups in age, BMI, neck diameter, and LDL cholesterol level.

“Does obstructive sleep apnea cause lower testosterone levels, or do lower testosterone levels cause obstructive sleep apnea?” Ms. Schmidt asked. “It's unclear. Chronic hypoxemia could cause some brief atrophy, which could possibly [affect] the hypothalamus-pituitary axis.”

Limitations of the study include the fact that the range of testosterone levels was limited to 200–350 ng/dL and the evaluation did not include overnight polysomnography.

CARMEL, CALIF. — Low baseline total serum testosterone levels could be a marker for obstructive sleep apnea in older men, Yao Schmidt reported at the Western regional meeting of the American Federation for Medical Research.

Of men aged 60–80 years, 20%–60% have borderline hypogonadism, said Ms. Schmidt, who is a second-year medical student at the University of Colorado Health Sciences Center, Denver.

She and associates evaluated 28 men aged 60–80 years. They recorded apnea-hypopnea index (AHI), baseline total serum testosterone level, age, body mass index (BMI), neck size, and LDL cholesterol level. Mean age was 67 years, mean BMI was 29 kg/m

Patients were divided into two groups: 14 with obstructive sleep apnea, defined as having an AHI of 10 or greater, and 14 men without.

Mean baseline serum testosterone level in the men with obstructive sleep apnea was 262 ng/dL, compared with a mean of 315 ng/dL in the men without, which was statistically significant. There were no significant differences between groups in age, BMI, neck diameter, and LDL cholesterol level.

“Does obstructive sleep apnea cause lower testosterone levels, or do lower testosterone levels cause obstructive sleep apnea?” Ms. Schmidt asked. “It's unclear. Chronic hypoxemia could cause some brief atrophy, which could possibly [affect] the hypothalamus-pituitary axis.”

Limitations of the study include the fact that the range of testosterone levels was limited to 200–350 ng/dL and the evaluation did not include overnight polysomnography.

CARMEL, CALIF. — Low baseline total serum testosterone levels could be a marker for obstructive sleep apnea in older men, Yao Schmidt reported at the Western regional meeting of the American Federation for Medical Research.

Of men aged 60–80 years, 20%–60% have borderline hypogonadism, said Ms. Schmidt, who is a second-year medical student at the University of Colorado Health Sciences Center, Denver.

She and associates evaluated 28 men aged 60–80 years. They recorded apnea-hypopnea index (AHI), baseline total serum testosterone level, age, body mass index (BMI), neck size, and LDL cholesterol level. Mean age was 67 years, mean BMI was 29 kg/m

Patients were divided into two groups: 14 with obstructive sleep apnea, defined as having an AHI of 10 or greater, and 14 men without.

Mean baseline serum testosterone level in the men with obstructive sleep apnea was 262 ng/dL, compared with a mean of 315 ng/dL in the men without, which was statistically significant. There were no significant differences between groups in age, BMI, neck diameter, and LDL cholesterol level.

“Does obstructive sleep apnea cause lower testosterone levels, or do lower testosterone levels cause obstructive sleep apnea?” Ms. Schmidt asked. “It's unclear. Chronic hypoxemia could cause some brief atrophy, which could possibly [affect] the hypothalamus-pituitary axis.”

Limitations of the study include the fact that the range of testosterone levels was limited to 200–350 ng/dL and the evaluation did not include overnight polysomnography.

CORONADO, CALIF. — Dermatoscopy can identify melanomas as small as 3 mm, but should be combined with a careful exam for the best diagnosis, Dr. James W. Steger said at an update on melanoma sponsored by the Scripps Clinic.

Researchers evaluated 349 consecutive patients who had 375 suspicious lesions requiring biopsy. Of these, 161 were 6 mm or smaller and 13 were melanomas. Clinical diagnosis alone detected 10 of 13, for a sensitivity of 77% and a specificity of 74%. Dermatoscopy alone also detected 10 of 13. Clinical and dermatoscopy criteria combined detected all 13 (Eur. J. Dermatol. 2002;12:573–6).

In a follow-up study, the researchers compared clinical exam with dermatoscopy for diagnosing 203 sequential pigmented lesions smaller than 3 mm in diameter (Br. J. Dermatol. 2006;155:570–3). In this study, 10 of 23 melanomas were diagnosed by clinical exam alone while dermatoscopy using Menzies score picked up 19 of the 23, which means that, for “very small melanoma [3 mm and under] the diagnostic rate of dermatoscopy is about double what it is for the naked eye,” said Dr. Steger, chair of the department of dermatology at Naval Medical Center San Diego. He then discussed two easy screening algorithms in dermatoscopy.

The first is the three-color test. After review of 74 pigmented lesions referred for excision, the most powerful criterion correlating with a histopathologic diagnosis of melanoma was the presence of three or more colors seen in the lesion on dermatoscopy. Sensitivity was 92%. Specificity was only 51% (Br. J. Dermatol. 2002;146:481–4).

“That's okay, since this is a screening technique,” Dr. Steger said.

The second algorithm is the three-criteria checklist. Criteria include asymmetry of color or dermoscopic structures, atypical pigment network, a “tennis net-like” pattern of irregular holes and thick lines, and the presence of any type of blue or white colors (Dermatology 2004;208:27–31).

Six nonexperts underwent 1 hour of training and applied the criteria to 231 consecutively excised pigmented lesions. Results were compared with those of an expert who used dermatoscopy with the pattern analysis method of diagnosis.

The nonexperts had a sensitivity of 96% and a specificity of 33%. The expert had a sensitivity of 90% and specificity of 94% using dermatoscopy.

The most powerful criterion correlating with the diagnosis is the presence of three or more colors in the lesion. Courtesy Dr. James W. Steger

CORONADO, CALIF. — Dermatoscopy can identify melanomas as small as 3 mm, but should be combined with a careful exam for the best diagnosis, Dr. James W. Steger said at an update on melanoma sponsored by the Scripps Clinic.

Researchers evaluated 349 consecutive patients who had 375 suspicious lesions requiring biopsy. Of these, 161 were 6 mm or smaller and 13 were melanomas. Clinical diagnosis alone detected 10 of 13, for a sensitivity of 77% and a specificity of 74%. Dermatoscopy alone also detected 10 of 13. Clinical and dermatoscopy criteria combined detected all 13 (Eur. J. Dermatol. 2002;12:573–6).

In a follow-up study, the researchers compared clinical exam with dermatoscopy for diagnosing 203 sequential pigmented lesions smaller than 3 mm in diameter (Br. J. Dermatol. 2006;155:570–3). In this study, 10 of 23 melanomas were diagnosed by clinical exam alone while dermatoscopy using Menzies score picked up 19 of the 23, which means that, for “very small melanoma [3 mm and under] the diagnostic rate of dermatoscopy is about double what it is for the naked eye,” said Dr. Steger, chair of the department of dermatology at Naval Medical Center San Diego. He then discussed two easy screening algorithms in dermatoscopy.

The first is the three-color test. After review of 74 pigmented lesions referred for excision, the most powerful criterion correlating with a histopathologic diagnosis of melanoma was the presence of three or more colors seen in the lesion on dermatoscopy. Sensitivity was 92%. Specificity was only 51% (Br. J. Dermatol. 2002;146:481–4).

“That's okay, since this is a screening technique,” Dr. Steger said.

The second algorithm is the three-criteria checklist. Criteria include asymmetry of color or dermoscopic structures, atypical pigment network, a “tennis net-like” pattern of irregular holes and thick lines, and the presence of any type of blue or white colors (Dermatology 2004;208:27–31).

Six nonexperts underwent 1 hour of training and applied the criteria to 231 consecutively excised pigmented lesions. Results were compared with those of an expert who used dermatoscopy with the pattern analysis method of diagnosis.

The nonexperts had a sensitivity of 96% and a specificity of 33%. The expert had a sensitivity of 90% and specificity of 94% using dermatoscopy.

The most powerful criterion correlating with the diagnosis is the presence of three or more colors in the lesion. Courtesy Dr. James W. Steger

CORONADO, CALIF. — Dermatoscopy can identify melanomas as small as 3 mm, but should be combined with a careful exam for the best diagnosis, Dr. James W. Steger said at an update on melanoma sponsored by the Scripps Clinic.

Researchers evaluated 349 consecutive patients who had 375 suspicious lesions requiring biopsy. Of these, 161 were 6 mm or smaller and 13 were melanomas. Clinical diagnosis alone detected 10 of 13, for a sensitivity of 77% and a specificity of 74%. Dermatoscopy alone also detected 10 of 13. Clinical and dermatoscopy criteria combined detected all 13 (Eur. J. Dermatol. 2002;12:573–6).

In a follow-up study, the researchers compared clinical exam with dermatoscopy for diagnosing 203 sequential pigmented lesions smaller than 3 mm in diameter (Br. J. Dermatol. 2006;155:570–3). In this study, 10 of 23 melanomas were diagnosed by clinical exam alone while dermatoscopy using Menzies score picked up 19 of the 23, which means that, for “very small melanoma [3 mm and under] the diagnostic rate of dermatoscopy is about double what it is for the naked eye,” said Dr. Steger, chair of the department of dermatology at Naval Medical Center San Diego. He then discussed two easy screening algorithms in dermatoscopy.

The first is the three-color test. After review of 74 pigmented lesions referred for excision, the most powerful criterion correlating with a histopathologic diagnosis of melanoma was the presence of three or more colors seen in the lesion on dermatoscopy. Sensitivity was 92%. Specificity was only 51% (Br. J. Dermatol. 2002;146:481–4).

“That's okay, since this is a screening technique,” Dr. Steger said.

The second algorithm is the three-criteria checklist. Criteria include asymmetry of color or dermoscopic structures, atypical pigment network, a “tennis net-like” pattern of irregular holes and thick lines, and the presence of any type of blue or white colors (Dermatology 2004;208:27–31).

Six nonexperts underwent 1 hour of training and applied the criteria to 231 consecutively excised pigmented lesions. Results were compared with those of an expert who used dermatoscopy with the pattern analysis method of diagnosis.

The nonexperts had a sensitivity of 96% and a specificity of 33%. The expert had a sensitivity of 90% and specificity of 94% using dermatoscopy.

The most powerful criterion correlating with the diagnosis is the presence of three or more colors in the lesion. Courtesy Dr. James W. Steger

To access the document, click on “practice parameters” from AACAP's home Web page at www.aacap.org

The American Academy of Child and Adolescent Psychiatry has released an updated version of its 10-year-old practice parameter for the assessment and treatment of children and adolescents with attention-deficit hyperactivity disorder.

An underlying theme of the parameter, released last month, is the recognition that the diagnosis and treatment of ADHD are “in the mainstream of American medicine and American psychiatry,” lead author Dr. Steven R. Pliszka said in an interview.

“ADHD is an international phenomenon now. It's no different from screening for asthma or diabetes or treating those conditions,” he added.

“We have an equal degree of evidence of the biological causes and effective treatments,” said Dr. Pliszka, chief of adolescent psychiatry at the University of Texas, San Antonio. “We want everyone to recognize that and go forward and help their patients.”

In a process that began in late 2004, Dr. Pliszka and his associates assembled 13 recommendations based on a review of nearly 5,000 references related to the diagnosis and treatment of ADHD that were generated between 1996 and 2006. These included references from the 1997 version of the practice parameter, as well as those that appeared in the scientific medical literature, in book chapters, or at scientific meetings.

Two chief developments drove the need to update the parameter, Dr. Pliszka said. One is the proliferation of new treatments for ADHD that have emerged in the last 5–10 years.

Another is what he called “a growth of genetics and neuroimaging studies that are starting to point the way to the underlying causes and brain features of the disorder.”

One recommendation in the 44-page document that differs from the 1997 version is based in part on results from the National Institute of Mental Health-sponsored multimodal treatment study of children with ADHD, which examined different treatment options for the disorder (Arch. Gen. Psychiatry 1999;56:1073–86). It concluded that careful medication management alone was superior to behavioral therapy and to routine community care that included medication.

“While there's debate about exactly how to interpret that study, I think for the child who just has ADHD and no other complicating condition, medication treatment appears to be most effective by itself,” Dr. Pliszka said.

In contrast, if the child has ADHD in combination with other problems like learning disabilities, behavior disorders, or depression, then he or she needs a combined approach: the medication and some type of psychosocial intervention, he noted.

“We don't recommend behavioral intervention alone except in milder cases or in cases where the diagnosis is in question,” said Dr. Pliszka.

Other recommendations address medications used for ADHD. They conclude that stimulant medications are usually the best first-line treatment options.

The current stimulants on the market “tend to be equally efficacious, and it's largely a matter of family and physician preference as to which one you use,” Dr. Pliszka said.

The nonstimulant atomoxetine (Strattera) may be considered as a first-line treatment “in certain situations like co-occurring anxiety and tics,” he said.

Dr. Martin T. Stein, a developmental-behavioral pediatrician at Rady Children's Hospital in San Diego who was not involved in assembling the recommendations, called the new practice parameter a valuable reference for child psychiatrists and general pediatricians alike.

“I think it's quite good,” Dr. Stein, who is also a professor of pediatrics at the University of California, San Diego, said in an interview. “There are so many areas where psychiatric practice and pediatric practice overlap and complement each other in this document.” Any physician who treats children could read this and find it quite valuable for practice, he said.

The document notes that there may be a place in ADHD treatment for medications not approved by the Food and Drug Administration, but which have demonstrated efficacy in some studies. These include bupropion, tricyclic antidepressants, and αagonists.

“These should only be tried if the ones in the approved group have failed,” Dr. Pliszka said.

The document also addresses concerns about the potential for rare side effects from stimulant use, including aggression and mood lability.

“In controlled trials, there is no evidence that the stimulants produce these [side effects] in numbers greater than in the placebo groups,” Dr. Pliszka said. “We acknowledge that they've been reported in postmarketing studies and that physicians should be alert to them, but there's not any undue concern. They shouldn't be a reason that people would shy away from using the medication.”

As for concerns about possible cardiovascular side effects based on reports of sudden deaths in people taking certain agents used in ADHD treatment, Dr. Pliszka and his associates concluded in the document that the rates of sudden death of children on ADHD medications “do not appear to exceed the base rate of sudden death in the general population.”

In the interview, Dr. Pliszka emphasized that he and his associates “do not view cardiovascular side effects as a risk of the stimulants. The one group to be cautious with are those people that already have some pre-existing heart disease.”

He predicted that neuroimaging is going to lead ADHD research efforts in the future, but emphasized that, at this time, neuroimaging “shouldn't be used commercially to diagnose ADHD. The diagnosis is still made by the efforts of the physician talking to the family, talking to the child, and gathering data about behavior.”

Dr. Pliszka disclosed that he receives or has received research support, acted as a consultant, and/or serves on a speakers' bureau for Shire Pharmaceuticals Group, McNeil Pediatrics, and Eli Lilly & Co.

The document notes that there may be a place in ADHD treatment for medications not approved by the FDA. DR. PLISZKA

To access the document, click on “practice parameters” from AACAP's home Web page at www.aacap.org

The American Academy of Child and Adolescent Psychiatry has released an updated version of its 10-year-old practice parameter for the assessment and treatment of children and adolescents with attention-deficit hyperactivity disorder.

An underlying theme of the parameter, released last month, is the recognition that the diagnosis and treatment of ADHD are “in the mainstream of American medicine and American psychiatry,” lead author Dr. Steven R. Pliszka said in an interview.

“ADHD is an international phenomenon now. It's no different from screening for asthma or diabetes or treating those conditions,” he added.

“We have an equal degree of evidence of the biological causes and effective treatments,” said Dr. Pliszka, chief of adolescent psychiatry at the University of Texas, San Antonio. “We want everyone to recognize that and go forward and help their patients.”

In a process that began in late 2004, Dr. Pliszka and his associates assembled 13 recommendations based on a review of nearly 5,000 references related to the diagnosis and treatment of ADHD that were generated between 1996 and 2006. These included references from the 1997 version of the practice parameter, as well as those that appeared in the scientific medical literature, in book chapters, or at scientific meetings.

Two chief developments drove the need to update the parameter, Dr. Pliszka said. One is the proliferation of new treatments for ADHD that have emerged in the last 5–10 years.

Another is what he called “a growth of genetics and neuroimaging studies that are starting to point the way to the underlying causes and brain features of the disorder.”

One recommendation in the 44-page document that differs from the 1997 version is based in part on results from the National Institute of Mental Health-sponsored multimodal treatment study of children with ADHD, which examined different treatment options for the disorder (Arch. Gen. Psychiatry 1999;56:1073–86). It concluded that careful medication management alone was superior to behavioral therapy and to routine community care that included medication.

“While there's debate about exactly how to interpret that study, I think for the child who just has ADHD and no other complicating condition, medication treatment appears to be most effective by itself,” Dr. Pliszka said.

In contrast, if the child has ADHD in combination with other problems like learning disabilities, behavior disorders, or depression, then he or she needs a combined approach: the medication and some type of psychosocial intervention, he noted.

“We don't recommend behavioral intervention alone except in milder cases or in cases where the diagnosis is in question,” said Dr. Pliszka.

Other recommendations address medications used for ADHD. They conclude that stimulant medications are usually the best first-line treatment options.

The current stimulants on the market “tend to be equally efficacious, and it's largely a matter of family and physician preference as to which one you use,” Dr. Pliszka said.

The nonstimulant atomoxetine (Strattera) may be considered as a first-line treatment “in certain situations like co-occurring anxiety and tics,” he said.

Dr. Martin T. Stein, a developmental-behavioral pediatrician at Rady Children's Hospital in San Diego who was not involved in assembling the recommendations, called the new practice parameter a valuable reference for child psychiatrists and general pediatricians alike.

“I think it's quite good,” Dr. Stein, who is also a professor of pediatrics at the University of California, San Diego, said in an interview. “There are so many areas where psychiatric practice and pediatric practice overlap and complement each other in this document.” Any physician who treats children could read this and find it quite valuable for practice, he said.

The document notes that there may be a place in ADHD treatment for medications not approved by the Food and Drug Administration, but which have demonstrated efficacy in some studies. These include bupropion, tricyclic antidepressants, and αagonists.

“These should only be tried if the ones in the approved group have failed,” Dr. Pliszka said.

The document also addresses concerns about the potential for rare side effects from stimulant use, including aggression and mood lability.

“In controlled trials, there is no evidence that the stimulants produce these [side effects] in numbers greater than in the placebo groups,” Dr. Pliszka said. “We acknowledge that they've been reported in postmarketing studies and that physicians should be alert to them, but there's not any undue concern. They shouldn't be a reason that people would shy away from using the medication.”

As for concerns about possible cardiovascular side effects based on reports of sudden deaths in people taking certain agents used in ADHD treatment, Dr. Pliszka and his associates concluded in the document that the rates of sudden death of children on ADHD medications “do not appear to exceed the base rate of sudden death in the general population.”

In the interview, Dr. Pliszka emphasized that he and his associates “do not view cardiovascular side effects as a risk of the stimulants. The one group to be cautious with are those people that already have some pre-existing heart disease.”

He predicted that neuroimaging is going to lead ADHD research efforts in the future, but emphasized that, at this time, neuroimaging “shouldn't be used commercially to diagnose ADHD. The diagnosis is still made by the efforts of the physician talking to the family, talking to the child, and gathering data about behavior.”

Dr. Pliszka disclosed that he receives or has received research support, acted as a consultant, and/or serves on a speakers' bureau for Shire Pharmaceuticals Group, McNeil Pediatrics, and Eli Lilly & Co.

The document notes that there may be a place in ADHD treatment for medications not approved by the FDA. DR. PLISZKA

To access the document, click on “practice parameters” from AACAP's home Web page at www.aacap.org

The American Academy of Child and Adolescent Psychiatry has released an updated version of its 10-year-old practice parameter for the assessment and treatment of children and adolescents with attention-deficit hyperactivity disorder.

An underlying theme of the parameter, released last month, is the recognition that the diagnosis and treatment of ADHD are “in the mainstream of American medicine and American psychiatry,” lead author Dr. Steven R. Pliszka said in an interview.

“ADHD is an international phenomenon now. It's no different from screening for asthma or diabetes or treating those conditions,” he added.

“We have an equal degree of evidence of the biological causes and effective treatments,” said Dr. Pliszka, chief of adolescent psychiatry at the University of Texas, San Antonio. “We want everyone to recognize that and go forward and help their patients.”

In a process that began in late 2004, Dr. Pliszka and his associates assembled 13 recommendations based on a review of nearly 5,000 references related to the diagnosis and treatment of ADHD that were generated between 1996 and 2006. These included references from the 1997 version of the practice parameter, as well as those that appeared in the scientific medical literature, in book chapters, or at scientific meetings.

Two chief developments drove the need to update the parameter, Dr. Pliszka said. One is the proliferation of new treatments for ADHD that have emerged in the last 5–10 years.

Another is what he called “a growth of genetics and neuroimaging studies that are starting to point the way to the underlying causes and brain features of the disorder.”

One recommendation in the 44-page document that differs from the 1997 version is based in part on results from the National Institute of Mental Health-sponsored multimodal treatment study of children with ADHD, which examined different treatment options for the disorder (Arch. Gen. Psychiatry 1999;56:1073–86). It concluded that careful medication management alone was superior to behavioral therapy and to routine community care that included medication.

“While there's debate about exactly how to interpret that study, I think for the child who just has ADHD and no other complicating condition, medication treatment appears to be most effective by itself,” Dr. Pliszka said.

In contrast, if the child has ADHD in combination with other problems like learning disabilities, behavior disorders, or depression, then he or she needs a combined approach: the medication and some type of psychosocial intervention, he noted.

“We don't recommend behavioral intervention alone except in milder cases or in cases where the diagnosis is in question,” said Dr. Pliszka.

Other recommendations address medications used for ADHD. They conclude that stimulant medications are usually the best first-line treatment options.

The current stimulants on the market “tend to be equally efficacious, and it's largely a matter of family and physician preference as to which one you use,” Dr. Pliszka said.

The nonstimulant atomoxetine (Strattera) may be considered as a first-line treatment “in certain situations like co-occurring anxiety and tics,” he said.

Dr. Martin T. Stein, a developmental-behavioral pediatrician at Rady Children's Hospital in San Diego who was not involved in assembling the recommendations, called the new practice parameter a valuable reference for child psychiatrists and general pediatricians alike.

“I think it's quite good,” Dr. Stein, who is also a professor of pediatrics at the University of California, San Diego, said in an interview. “There are so many areas where psychiatric practice and pediatric practice overlap and complement each other in this document.” Any physician who treats children could read this and find it quite valuable for practice, he said.

The document notes that there may be a place in ADHD treatment for medications not approved by the Food and Drug Administration, but which have demonstrated efficacy in some studies. These include bupropion, tricyclic antidepressants, and αagonists.

“These should only be tried if the ones in the approved group have failed,” Dr. Pliszka said.

The document also addresses concerns about the potential for rare side effects from stimulant use, including aggression and mood lability.

“In controlled trials, there is no evidence that the stimulants produce these [side effects] in numbers greater than in the placebo groups,” Dr. Pliszka said. “We acknowledge that they've been reported in postmarketing studies and that physicians should be alert to them, but there's not any undue concern. They shouldn't be a reason that people would shy away from using the medication.”

As for concerns about possible cardiovascular side effects based on reports of sudden deaths in people taking certain agents used in ADHD treatment, Dr. Pliszka and his associates concluded in the document that the rates of sudden death of children on ADHD medications “do not appear to exceed the base rate of sudden death in the general population.”

In the interview, Dr. Pliszka emphasized that he and his associates “do not view cardiovascular side effects as a risk of the stimulants. The one group to be cautious with are those people that already have some pre-existing heart disease.”

He predicted that neuroimaging is going to lead ADHD research efforts in the future, but emphasized that, at this time, neuroimaging “shouldn't be used commercially to diagnose ADHD. The diagnosis is still made by the efforts of the physician talking to the family, talking to the child, and gathering data about behavior.”

Dr. Pliszka disclosed that he receives or has received research support, acted as a consultant, and/or serves on a speakers' bureau for Shire Pharmaceuticals Group, McNeil Pediatrics, and Eli Lilly & Co.

The document notes that there may be a place in ADHD treatment for medications not approved by the FDA. DR. PLISZKA

SAN DIEGO — Current screening and surveillance guidelines for Barrett's esophagus and associated neoplasia are not supported by strong evidence, Dr. Marcia Irene Canto said at a meeting jointly sponsored by the AGA Institute and the Japanese Society of Gastroenterology.

“There is currently insufficient evidence for sedated esophagogastroduodenoscopy [EGD] screening, but it may be more cost effective than surveillance if only Barrett's patients with dysplasia diagnosed by screening are then followed,” said Dr. Canto, director of clinical research in the division of gastroenterology and hepatology at Johns Hopkins University, Baltimore.

As for current surveillance practices, “the biopsy protocol detects cancer, but current guidelines regarding increased surveillance intervals in Barrett's patients without dysplasia would lead to missed high-grade dysplasia and cancer,” she said. “We need better endoscopic techniques and better risk stratification.”

Dr. Canto explained that current practices for screening and surveillance of Barrett's esophagus are not based on randomized, controlled trials (level I evidence) or even well-designed cohort or case-control trials (level II evidence). Rather, current practice is based on decision analyses, case series, case reports, or flawed clinical trials (level III evidence), opinions of expert authorities based on clinical evidence, descriptive studies, or reports of expert committees (level IV evidence), and insufficient evidence to form an opinion (level V evidence).

“The rationale for screening and surveillance is to improve survival, but more and more we are trying to prevent cancer in Barrett's patients,” she said. “It's a different approach, by detecting high-grade dysplasia and intervening with ablation endoscopic mucosal resection or esophagectomy in this precancerous phase.”

Data on 783 patients from five prospective studies and one patient registry suggest that the risk of cancer in Barrett's esophagus is related to the grade of dysplasia. The risk for patients with no dysplasia stands at 2%, while the risk for those with low-grade and high-grade dysplasia is 7% and 22%, respectively.

Dr. Canto noted that there are no randomized, controlled trials on the evidence for surveillance in Barrett's esophagus, only three retrospective case series and one ongoing prospective study. But data from those studies indicate that the 2-year survival rate seems to be improved for patients who undergo surveillance, compared with those who don't (86% vs. 46%). “And an economic analysis of surveillance in general suggests that if you target patients with dysplastic Barrett's, it probably is cost effective,” she said.

The evidence against surveillance is largely based on the fact that most Barrett's patients die from other causes. “When you look prospectively, the risk of cancer in Barrett's is really low: about 0.5%–1.2% per year,” she added. “Therefore, EGD, which is the standard way of doing surveillance, is very costly.”

Moreover, the optimal surveillance technique remains unknown. “Across the United States there is such inconsistency in techniques for surveillance,” she said. “Many practicing gastroenterologists do not follow any particular biopsy or surveillance technique.”

Since clinicians at Johns Hopkins began endoscopic surveillance in 1994, the prevalence of occult cancer in 39 Barrett's patients with high-grade dysplasia has decreased from 43% to 21%. None of the 15 patients who had some type of biopsy protocol or imaging technique implemented in their surveillance had occult cancer, while 8 of the 24 who did not follow a biopsy protocol clearly had occult cancer. “This is even with modern endoscopy techniques, so there is some benefit to trying to do that,” Dr. Canto said.

For a Barrett's patient with no dysplasia, the American Gastroenterological Association (AGA) recommends a second EGD 1 year later, and then surveillance every 5 years (Gastroenterology 2005;128:1468–70).

The American College of Gastroenterology (ACG) guidelines are similar, but recommend surveillance every 3 years (Am. J. Gastroenterol. 2002;97:1888–95).

“Is this evidence-based?” Dr. Canto asked. “Guidelines written by the GI societies are based on current data and decision analyses in terms of what the best surveillance interval is. There will never be the equivalent of the National Polyp Study for colon cancer surveillance.”

For a Barrett's patient with low-grade dysplasia, the AGA recommends an EGD every 6 months for 1 year, then increasing the surveillance interval to every 1–2 years. The ACG guidelines are similar, but they recommend surveillance every year.

For a Barrett's patient with high-grade dysplasia, the American Society for Gastrointestinal Endoscopy recommends confirming the diagnosis with two experienced pathologists and then offering the patient surgery or endoscopic therapy (Gastrointest. Endosc. 2006;63:570–80). The patient should then undergo surveillance every 3 months for at least 2 years.

The ACG guidelines are similar but recommend endoscopic mucosal resection for more severe disease.

Preliminary results from a prospective multicenter study of 618 patients show that the prevalent cancer risk within 1 year of diagnosing the index lesion was 6.7% (Clin. Gastroenterol. Hepatol. 2006;4:566–72). Furthermore, when the researchers followed the patients, the risk of cancer in patients with no dysplasia was 0.5% per year while the risk of cancer in patients with low-grade dysplasia was similar at 0.6% per year.

So far, regression of low-grade dysplasia has occurred in 66% of patients. Dr. Canto pointed out that 53% of the incident high-grade dysplasias or cancers developed after two EGDs with no dysplasia. “So what if you have the patient back at year 5 according to the AGA guidelines, but the patient developed a Barrett's cancer or high-grade dysplasia in year 2?” she asked. “We don't have the evidence for increasing the surveillance intervals. In fact, preliminary evidence from this paper suggests that Barrett's high-grade dysplasia or cancer might be missed if you followed the AGA guidelines.”

Screening for Barrett's esophagus and associated neoplasia presents another quagmire. The ACG guidelines state that patients with chronic GERD symptoms are most likely to have Barrett's esophagus and should undergo upper endoscopy, but an AGA technical review concluded that there is no direct evidence that has validated the use of screening for esophageal cancer in the United States.

Dr. Canto said that this is in part because 40% of Barrett's patients with cancer have no GERD symptoms and fewer than 4% have Barrett's diagnosed before the cancer is diagnosed.

One study concluded that screening 50-year-old men with symptoms of GERD to detect adenocarcinoma associated with Barrett's esophagus is probably cost effective, but continuing surveillance of patients who have Barrett's esophagus but no dysplasia is costly, even if screening occurs at 5-year intervals (Ann. Intern. Med. 2003;138:176–86).

Candidates for screening include patients with erosive esophagitis, those with chronic severe GERD, white males over age 50 regardless of symptoms, those with a family history of Barrett's and adenocarcinoma, those who are obese, and postcholecystectomy patients (Am. J. Gastroenterol. 2004;99:2107–14).

Current endoscopic tools for screening include a standard videoendoscope (sedated or unsedated), an unsedated thin videoendoscope, an office-based thin battery-powered endoscope, and wireless capsule endoscopy.

Histology slide shows low-grade dysplasia in a biopsy sample obtained from a patient with Barrett's esophagus. Courtesy Dr. Marcia Irene Canto

SAN DIEGO — Current screening and surveillance guidelines for Barrett's esophagus and associated neoplasia are not supported by strong evidence, Dr. Marcia Irene Canto said at a meeting jointly sponsored by the AGA Institute and the Japanese Society of Gastroenterology.

“There is currently insufficient evidence for sedated esophagogastroduodenoscopy [EGD] screening, but it may be more cost effective than surveillance if only Barrett's patients with dysplasia diagnosed by screening are then followed,” said Dr. Canto, director of clinical research in the division of gastroenterology and hepatology at Johns Hopkins University, Baltimore.

As for current surveillance practices, “the biopsy protocol detects cancer, but current guidelines regarding increased surveillance intervals in Barrett's patients without dysplasia would lead to missed high-grade dysplasia and cancer,” she said. “We need better endoscopic techniques and better risk stratification.”

Dr. Canto explained that current practices for screening and surveillance of Barrett's esophagus are not based on randomized, controlled trials (level I evidence) or even well-designed cohort or case-control trials (level II evidence). Rather, current practice is based on decision analyses, case series, case reports, or flawed clinical trials (level III evidence), opinions of expert authorities based on clinical evidence, descriptive studies, or reports of expert committees (level IV evidence), and insufficient evidence to form an opinion (level V evidence).

“The rationale for screening and surveillance is to improve survival, but more and more we are trying to prevent cancer in Barrett's patients,” she said. “It's a different approach, by detecting high-grade dysplasia and intervening with ablation endoscopic mucosal resection or esophagectomy in this precancerous phase.”

Data on 783 patients from five prospective studies and one patient registry suggest that the risk of cancer in Barrett's esophagus is related to the grade of dysplasia. The risk for patients with no dysplasia stands at 2%, while the risk for those with low-grade and high-grade dysplasia is 7% and 22%, respectively.

Dr. Canto noted that there are no randomized, controlled trials on the evidence for surveillance in Barrett's esophagus, only three retrospective case series and one ongoing prospective study. But data from those studies indicate that the 2-year survival rate seems to be improved for patients who undergo surveillance, compared with those who don't (86% vs. 46%). “And an economic analysis of surveillance in general suggests that if you target patients with dysplastic Barrett's, it probably is cost effective,” she said.

The evidence against surveillance is largely based on the fact that most Barrett's patients die from other causes. “When you look prospectively, the risk of cancer in Barrett's is really low: about 0.5%–1.2% per year,” she added. “Therefore, EGD, which is the standard way of doing surveillance, is very costly.”

Moreover, the optimal surveillance technique remains unknown. “Across the United States there is such inconsistency in techniques for surveillance,” she said. “Many practicing gastroenterologists do not follow any particular biopsy or surveillance technique.”

Since clinicians at Johns Hopkins began endoscopic surveillance in 1994, the prevalence of occult cancer in 39 Barrett's patients with high-grade dysplasia has decreased from 43% to 21%. None of the 15 patients who had some type of biopsy protocol or imaging technique implemented in their surveillance had occult cancer, while 8 of the 24 who did not follow a biopsy protocol clearly had occult cancer. “This is even with modern endoscopy techniques, so there is some benefit to trying to do that,” Dr. Canto said.

For a Barrett's patient with no dysplasia, the American Gastroenterological Association (AGA) recommends a second EGD 1 year later, and then surveillance every 5 years (Gastroenterology 2005;128:1468–70).

The American College of Gastroenterology (ACG) guidelines are similar, but recommend surveillance every 3 years (Am. J. Gastroenterol. 2002;97:1888–95).

“Is this evidence-based?” Dr. Canto asked. “Guidelines written by the GI societies are based on current data and decision analyses in terms of what the best surveillance interval is. There will never be the equivalent of the National Polyp Study for colon cancer surveillance.”

For a Barrett's patient with low-grade dysplasia, the AGA recommends an EGD every 6 months for 1 year, then increasing the surveillance interval to every 1–2 years. The ACG guidelines are similar, but they recommend surveillance every year.

For a Barrett's patient with high-grade dysplasia, the American Society for Gastrointestinal Endoscopy recommends confirming the diagnosis with two experienced pathologists and then offering the patient surgery or endoscopic therapy (Gastrointest. Endosc. 2006;63:570–80). The patient should then undergo surveillance every 3 months for at least 2 years.

The ACG guidelines are similar but recommend endoscopic mucosal resection for more severe disease.

Preliminary results from a prospective multicenter study of 618 patients show that the prevalent cancer risk within 1 year of diagnosing the index lesion was 6.7% (Clin. Gastroenterol. Hepatol. 2006;4:566–72). Furthermore, when the researchers followed the patients, the risk of cancer in patients with no dysplasia was 0.5% per year while the risk of cancer in patients with low-grade dysplasia was similar at 0.6% per year.

So far, regression of low-grade dysplasia has occurred in 66% of patients. Dr. Canto pointed out that 53% of the incident high-grade dysplasias or cancers developed after two EGDs with no dysplasia. “So what if you have the patient back at year 5 according to the AGA guidelines, but the patient developed a Barrett's cancer or high-grade dysplasia in year 2?” she asked. “We don't have the evidence for increasing the surveillance intervals. In fact, preliminary evidence from this paper suggests that Barrett's high-grade dysplasia or cancer might be missed if you followed the AGA guidelines.”

Screening for Barrett's esophagus and associated neoplasia presents another quagmire. The ACG guidelines state that patients with chronic GERD symptoms are most likely to have Barrett's esophagus and should undergo upper endoscopy, but an AGA technical review concluded that there is no direct evidence that has validated the use of screening for esophageal cancer in the United States.

Dr. Canto said that this is in part because 40% of Barrett's patients with cancer have no GERD symptoms and fewer than 4% have Barrett's diagnosed before the cancer is diagnosed.

One study concluded that screening 50-year-old men with symptoms of GERD to detect adenocarcinoma associated with Barrett's esophagus is probably cost effective, but continuing surveillance of patients who have Barrett's esophagus but no dysplasia is costly, even if screening occurs at 5-year intervals (Ann. Intern. Med. 2003;138:176–86).

Candidates for screening include patients with erosive esophagitis, those with chronic severe GERD, white males over age 50 regardless of symptoms, those with a family history of Barrett's and adenocarcinoma, those who are obese, and postcholecystectomy patients (Am. J. Gastroenterol. 2004;99:2107–14).

Current endoscopic tools for screening include a standard videoendoscope (sedated or unsedated), an unsedated thin videoendoscope, an office-based thin battery-powered endoscope, and wireless capsule endoscopy.

Histology slide shows low-grade dysplasia in a biopsy sample obtained from a patient with Barrett's esophagus. Courtesy Dr. Marcia Irene Canto

SAN DIEGO — Current screening and surveillance guidelines for Barrett's esophagus and associated neoplasia are not supported by strong evidence, Dr. Marcia Irene Canto said at a meeting jointly sponsored by the AGA Institute and the Japanese Society of Gastroenterology.

“There is currently insufficient evidence for sedated esophagogastroduodenoscopy [EGD] screening, but it may be more cost effective than surveillance if only Barrett's patients with dysplasia diagnosed by screening are then followed,” said Dr. Canto, director of clinical research in the division of gastroenterology and hepatology at Johns Hopkins University, Baltimore.

As for current surveillance practices, “the biopsy protocol detects cancer, but current guidelines regarding increased surveillance intervals in Barrett's patients without dysplasia would lead to missed high-grade dysplasia and cancer,” she said. “We need better endoscopic techniques and better risk stratification.”

Dr. Canto explained that current practices for screening and surveillance of Barrett's esophagus are not based on randomized, controlled trials (level I evidence) or even well-designed cohort or case-control trials (level II evidence). Rather, current practice is based on decision analyses, case series, case reports, or flawed clinical trials (level III evidence), opinions of expert authorities based on clinical evidence, descriptive studies, or reports of expert committees (level IV evidence), and insufficient evidence to form an opinion (level V evidence).

“The rationale for screening and surveillance is to improve survival, but more and more we are trying to prevent cancer in Barrett's patients,” she said. “It's a different approach, by detecting high-grade dysplasia and intervening with ablation endoscopic mucosal resection or esophagectomy in this precancerous phase.”

Data on 783 patients from five prospective studies and one patient registry suggest that the risk of cancer in Barrett's esophagus is related to the grade of dysplasia. The risk for patients with no dysplasia stands at 2%, while the risk for those with low-grade and high-grade dysplasia is 7% and 22%, respectively.

Dr. Canto noted that there are no randomized, controlled trials on the evidence for surveillance in Barrett's esophagus, only three retrospective case series and one ongoing prospective study. But data from those studies indicate that the 2-year survival rate seems to be improved for patients who undergo surveillance, compared with those who don't (86% vs. 46%). “And an economic analysis of surveillance in general suggests that if you target patients with dysplastic Barrett's, it probably is cost effective,” she said.

The evidence against surveillance is largely based on the fact that most Barrett's patients die from other causes. “When you look prospectively, the risk of cancer in Barrett's is really low: about 0.5%–1.2% per year,” she added. “Therefore, EGD, which is the standard way of doing surveillance, is very costly.”

Moreover, the optimal surveillance technique remains unknown. “Across the United States there is such inconsistency in techniques for surveillance,” she said. “Many practicing gastroenterologists do not follow any particular biopsy or surveillance technique.”

Since clinicians at Johns Hopkins began endoscopic surveillance in 1994, the prevalence of occult cancer in 39 Barrett's patients with high-grade dysplasia has decreased from 43% to 21%. None of the 15 patients who had some type of biopsy protocol or imaging technique implemented in their surveillance had occult cancer, while 8 of the 24 who did not follow a biopsy protocol clearly had occult cancer. “This is even with modern endoscopy techniques, so there is some benefit to trying to do that,” Dr. Canto said.

For a Barrett's patient with no dysplasia, the American Gastroenterological Association (AGA) recommends a second EGD 1 year later, and then surveillance every 5 years (Gastroenterology 2005;128:1468–70).

The American College of Gastroenterology (ACG) guidelines are similar, but recommend surveillance every 3 years (Am. J. Gastroenterol. 2002;97:1888–95).

“Is this evidence-based?” Dr. Canto asked. “Guidelines written by the GI societies are based on current data and decision analyses in terms of what the best surveillance interval is. There will never be the equivalent of the National Polyp Study for colon cancer surveillance.”

For a Barrett's patient with low-grade dysplasia, the AGA recommends an EGD every 6 months for 1 year, then increasing the surveillance interval to every 1–2 years. The ACG guidelines are similar, but they recommend surveillance every year.

For a Barrett's patient with high-grade dysplasia, the American Society for Gastrointestinal Endoscopy recommends confirming the diagnosis with two experienced pathologists and then offering the patient surgery or endoscopic therapy (Gastrointest. Endosc. 2006;63:570–80). The patient should then undergo surveillance every 3 months for at least 2 years.

The ACG guidelines are similar but recommend endoscopic mucosal resection for more severe disease.

Preliminary results from a prospective multicenter study of 618 patients show that the prevalent cancer risk within 1 year of diagnosing the index lesion was 6.7% (Clin. Gastroenterol. Hepatol. 2006;4:566–72). Furthermore, when the researchers followed the patients, the risk of cancer in patients with no dysplasia was 0.5% per year while the risk of cancer in patients with low-grade dysplasia was similar at 0.6% per year.

So far, regression of low-grade dysplasia has occurred in 66% of patients. Dr. Canto pointed out that 53% of the incident high-grade dysplasias or cancers developed after two EGDs with no dysplasia. “So what if you have the patient back at year 5 according to the AGA guidelines, but the patient developed a Barrett's cancer or high-grade dysplasia in year 2?” she asked. “We don't have the evidence for increasing the surveillance intervals. In fact, preliminary evidence from this paper suggests that Barrett's high-grade dysplasia or cancer might be missed if you followed the AGA guidelines.”

Screening for Barrett's esophagus and associated neoplasia presents another quagmire. The ACG guidelines state that patients with chronic GERD symptoms are most likely to have Barrett's esophagus and should undergo upper endoscopy, but an AGA technical review concluded that there is no direct evidence that has validated the use of screening for esophageal cancer in the United States.

Dr. Canto said that this is in part because 40% of Barrett's patients with cancer have no GERD symptoms and fewer than 4% have Barrett's diagnosed before the cancer is diagnosed.

One study concluded that screening 50-year-old men with symptoms of GERD to detect adenocarcinoma associated with Barrett's esophagus is probably cost effective, but continuing surveillance of patients who have Barrett's esophagus but no dysplasia is costly, even if screening occurs at 5-year intervals (Ann. Intern. Med. 2003;138:176–86).

Candidates for screening include patients with erosive esophagitis, those with chronic severe GERD, white males over age 50 regardless of symptoms, those with a family history of Barrett's and adenocarcinoma, those who are obese, and postcholecystectomy patients (Am. J. Gastroenterol. 2004;99:2107–14).

Current endoscopic tools for screening include a standard videoendoscope (sedated or unsedated), an unsedated thin videoendoscope, an office-based thin battery-powered endoscope, and wireless capsule endoscopy.

Histology slide shows low-grade dysplasia in a biopsy sample obtained from a patient with Barrett's esophagus. Courtesy Dr. Marcia Irene Canto

CARMEL, CALIF. — The evidence for using cholinesterase inhibitors in patients diagnosed with Alzheimer's disease “is pretty darned poor,” Dr. Laura Mosqueda said at the Western regional meeting of the American Federation for Medical Research.

She based her remarks on two recent meta-analyses of the topic. The first was a systematic review of randomized clinical trials of the cholinesterase inhibitors donepezil, rivastigmine, and galantamine.

In a search of the Medline, Embase, and Cochrane databases, researchers led by Dr. Hanna Kaduszkiewicz of Hamburg, Germany, evaluated 412 references published between 1989 and 2004 (BMJ 2005;331:321–7). Of these, 22 were included in the study.

In the 14 trials that used the Alzheimer's disease assessment scale-cognitive subscale, the mean difference between treatment and placebo groups ranged from 1.5 points to 3.9 points, which is a modest effect at best, said Dr. Mosqueda, director of geriatrics and a professor of family medicine at the University of California, Irvine.

In the 12 trials that used the Clinician's Interview-Based Impression of Change scale with caregiver input, the mean differences ranged from 0.26 to 0.54, “which is below what you're even allowed to score on the test,” she said, explaining that the rater is allowed to use only whole integers.

The incidence of adverse effects from the medications was 20% among those in the treatment group and 7% among those who took placebo. The most common adverse events were nausea, vomiting, diarrhea, and weight loss.

“How many times have we had somebody who comes in with Alzheimer's disease, they're losing weight and going through a major work-up, only to realize that they're on donepezil, and that this may be the cause of the weight loss?” Dr. Mosqueda asked.

She also highlighted a more recent Cochrane Review led by Dr. Jacqueline Birks of the University of Oxford (England). It was a meta-analysis of studies also involving the cholinesterase inhibitors donepezil, rivastigmine, and galantamine (Cochrane Database Syst. Rev. 2006;DOI: 10.1002/14651858.CD005593). The meta-analysis concluded that although these three cholinesterase inhibitors are modestly efficacious for mild to moderate Alzheimer's disease, there are no differences among them in terms of efficacy, even though the three drugs work in slightly different ways.

Despite the paucity of data showing efficacy, one factor that motivates physicians to prescribe cholinesterase inhibitors for Alzheimer's patients is the sense that they “really want to do something” for patients and their families, Dr. Mosqueda said. “It's much faster to write that prescription than to sit down, review the evidence, and go over the pros and cons with the patient and family. That takes time to do, but I think it's so important for people to understand, so that they can make an informed decision.”

The cost of medication can also be a downside for some Alzheimer's patients who have to pay out of pocket for cholinesterase inhibitors.

Dr. Mosqueda noted that for families faced with making a financial decision between paying for a cholinesterase inhibitor prescription and enrolling their loved one in an adult day care program, “that adult day care program is much more efficacious. Other, more important issues may not be addressed [with the medication alone]. Sometimes you can spend your time prescribing medicines instead of talking about other issues related to Alzheimer's disease.”

She concluded by saying that cholinesterase inhibitors “are nice, but all of us need comfort, identity, joy, and a big dose of love. That goes a long way when we're caring for people who have Alzheimer's disease and their families. Cholinesterase inhibitors may or may not be an adjunct to that.”

'It's much faster to write that prescription than to sit down … and go over the pros and cons.' DR. MOSQUEDA

CARMEL, CALIF. — The evidence for using cholinesterase inhibitors in patients diagnosed with Alzheimer's disease “is pretty darned poor,” Dr. Laura Mosqueda said at the Western regional meeting of the American Federation for Medical Research.

She based her remarks on two recent meta-analyses of the topic. The first was a systematic review of randomized clinical trials of the cholinesterase inhibitors donepezil, rivastigmine, and galantamine.

In a search of the Medline, Embase, and Cochrane databases, researchers led by Dr. Hanna Kaduszkiewicz of Hamburg, Germany, evaluated 412 references published between 1989 and 2004 (BMJ 2005;331:321–7). Of these, 22 were included in the study.

In the 14 trials that used the Alzheimer's disease assessment scale-cognitive subscale, the mean difference between treatment and placebo groups ranged from 1.5 points to 3.9 points, which is a modest effect at best, said Dr. Mosqueda, director of geriatrics and a professor of family medicine at the University of California, Irvine.

In the 12 trials that used the Clinician's Interview-Based Impression of Change scale with caregiver input, the mean differences ranged from 0.26 to 0.54, “which is below what you're even allowed to score on the test,” she said, explaining that the rater is allowed to use only whole integers.

The incidence of adverse effects from the medications was 20% among those in the treatment group and 7% among those who took placebo. The most common adverse events were nausea, vomiting, diarrhea, and weight loss.

“How many times have we had somebody who comes in with Alzheimer's disease, they're losing weight and going through a major work-up, only to realize that they're on donepezil, and that this may be the cause of the weight loss?” Dr. Mosqueda asked.

She also highlighted a more recent Cochrane Review led by Dr. Jacqueline Birks of the University of Oxford (England). It was a meta-analysis of studies also involving the cholinesterase inhibitors donepezil, rivastigmine, and galantamine (Cochrane Database Syst. Rev. 2006;DOI: 10.1002/14651858.CD005593). The meta-analysis concluded that although these three cholinesterase inhibitors are modestly efficacious for mild to moderate Alzheimer's disease, there are no differences among them in terms of efficacy, even though the three drugs work in slightly different ways.

Despite the paucity of data showing efficacy, one factor that motivates physicians to prescribe cholinesterase inhibitors for Alzheimer's patients is the sense that they “really want to do something” for patients and their families, Dr. Mosqueda said. “It's much faster to write that prescription than to sit down, review the evidence, and go over the pros and cons with the patient and family. That takes time to do, but I think it's so important for people to understand, so that they can make an informed decision.”

The cost of medication can also be a downside for some Alzheimer's patients who have to pay out of pocket for cholinesterase inhibitors.

Dr. Mosqueda noted that for families faced with making a financial decision between paying for a cholinesterase inhibitor prescription and enrolling their loved one in an adult day care program, “that adult day care program is much more efficacious. Other, more important issues may not be addressed [with the medication alone]. Sometimes you can spend your time prescribing medicines instead of talking about other issues related to Alzheimer's disease.”

She concluded by saying that cholinesterase inhibitors “are nice, but all of us need comfort, identity, joy, and a big dose of love. That goes a long way when we're caring for people who have Alzheimer's disease and their families. Cholinesterase inhibitors may or may not be an adjunct to that.”

'It's much faster to write that prescription than to sit down … and go over the pros and cons.' DR. MOSQUEDA

CARMEL, CALIF. — The evidence for using cholinesterase inhibitors in patients diagnosed with Alzheimer's disease “is pretty darned poor,” Dr. Laura Mosqueda said at the Western regional meeting of the American Federation for Medical Research.

She based her remarks on two recent meta-analyses of the topic. The first was a systematic review of randomized clinical trials of the cholinesterase inhibitors donepezil, rivastigmine, and galantamine.

In a search of the Medline, Embase, and Cochrane databases, researchers led by Dr. Hanna Kaduszkiewicz of Hamburg, Germany, evaluated 412 references published between 1989 and 2004 (BMJ 2005;331:321–7). Of these, 22 were included in the study.

In the 14 trials that used the Alzheimer's disease assessment scale-cognitive subscale, the mean difference between treatment and placebo groups ranged from 1.5 points to 3.9 points, which is a modest effect at best, said Dr. Mosqueda, director of geriatrics and a professor of family medicine at the University of California, Irvine.

In the 12 trials that used the Clinician's Interview-Based Impression of Change scale with caregiver input, the mean differences ranged from 0.26 to 0.54, “which is below what you're even allowed to score on the test,” she said, explaining that the rater is allowed to use only whole integers.

The incidence of adverse effects from the medications was 20% among those in the treatment group and 7% among those who took placebo. The most common adverse events were nausea, vomiting, diarrhea, and weight loss.

“How many times have we had somebody who comes in with Alzheimer's disease, they're losing weight and going through a major work-up, only to realize that they're on donepezil, and that this may be the cause of the weight loss?” Dr. Mosqueda asked.

She also highlighted a more recent Cochrane Review led by Dr. Jacqueline Birks of the University of Oxford (England). It was a meta-analysis of studies also involving the cholinesterase inhibitors donepezil, rivastigmine, and galantamine (Cochrane Database Syst. Rev. 2006;DOI: 10.1002/14651858.CD005593). The meta-analysis concluded that although these three cholinesterase inhibitors are modestly efficacious for mild to moderate Alzheimer's disease, there are no differences among them in terms of efficacy, even though the three drugs work in slightly different ways.

Despite the paucity of data showing efficacy, one factor that motivates physicians to prescribe cholinesterase inhibitors for Alzheimer's patients is the sense that they “really want to do something” for patients and their families, Dr. Mosqueda said. “It's much faster to write that prescription than to sit down, review the evidence, and go over the pros and cons with the patient and family. That takes time to do, but I think it's so important for people to understand, so that they can make an informed decision.”

The cost of medication can also be a downside for some Alzheimer's patients who have to pay out of pocket for cholinesterase inhibitors.

Dr. Mosqueda noted that for families faced with making a financial decision between paying for a cholinesterase inhibitor prescription and enrolling their loved one in an adult day care program, “that adult day care program is much more efficacious. Other, more important issues may not be addressed [with the medication alone]. Sometimes you can spend your time prescribing medicines instead of talking about other issues related to Alzheimer's disease.”

She concluded by saying that cholinesterase inhibitors “are nice, but all of us need comfort, identity, joy, and a big dose of love. That goes a long way when we're caring for people who have Alzheimer's disease and their families. Cholinesterase inhibitors may or may not be an adjunct to that.”

'It's much faster to write that prescription than to sit down … and go over the pros and cons.' DR. MOSQUEDA

LAS VEGAS — Not long ago, physicians were taught to believe that chronic back pain does not occur in children.

“But that just isn't true,” Dr. David L. Skaggs said at meeting sponsored by the American Academy of Pediatrics' California Chapters 1, 2, 3, and 4 and the AAP.

“We did a study of kids between the ages of 11 and 14, and found that 37% of them had back pain at any given time,” said Dr. Skaggs, associate director of the Children's Orthopedic Center at Children's Hospital Los Angeles. “So when a child comes in with back pain, it can be difficult to decide what's pathologic and what's not pathologic.”

If a child presents with diffuse back pain that is triggered by physical activity, that comes and goes over time with periods of no pain, and that does not get worse at night, this is probably nothing to worry about.

Worry when a child presents with point tenderness back pain, or what he calls the “positive finger test” on physical exam. The culprit could be spondylolysis, diskitis, or a tumor.

“If the child points at one place and says, 'It hurts there,' that's when you should be concerned,” he said. “Ask, 'Does it ever hurt at night, worse enough to wake you up? Is the pain getting worse?' If they say yes, you should order a MRI of the cervicothoracic lumbar spine.”

Dr. Skaggs also discussed the following spinal problems that can occur in children:

▸ Congenital muscular torticollis. In this condition, the child's head tilts laterally with the ear toward one shoulder while the chin is rotated toward the opposite shoulder. The cause is thought to be fibrosis or compartment syndrome of the sternocleidomastoid muscle. “Oftentimes, when the kids are born they may not have this position, but within a few weeks, it develops,” Dr. Skaggs said. “That's because it takes a while for the sternocleidomastoid muscle to fibrose or develop compartment sydrome after the trauma of birth.”

If picked up early and physical therapy is begun in a timely fashion, the condition remits more than 95% of the time within the first year of life. However, most case series report about a 5% association with developmental dysplasia of the hip, “so I recommend getting a screening ultrasound in an infant who has congenital muscular torticollis. There are not enough studies to make recommendations, but I think it makes common sense,” he said.

▸ Plagiocephaly. This usually is secondary to congenital muscular torticollis. The best treatment for this is to treat the torticollis. “Encourage the child to sleep with the head tilted in the opposite position of normal, and eventually the plagiocephaly will resolve spontaneously,” he said.

If the plagiocephaly doesn't resolve in 6–8 months, referral to a neurosurgeon or an expert in bracing is warranted. “I'm generally not the biggest fan of bracing for most things in orthopedics, but [using a brace for] this really seems to work,” said Dr. Skaggs, who is also a professor of orthopedics at the University of Southern California, Los Angeles.

▸ Late-onset torticollis. In this condition, which is most commonly due to C1-C2 rotatory subluxation, the sternocleidomastoid muscle is tight on the opposite side to where the ear is toward the chin. It's in spasm from being stretched to accommodate the head position.

“Most of the time, it resolves spontaneously in a few days,” he said. “If it does not resolve in a week, that means an instant referral to a specialist in pediatric spine disorders.”

A CT scan of C1-C2 with the head turned to the right and left makes the diagnosis in most cases. If detected within 1 week, treatment involves placement of a soft cervical collar.

If detected within 1 month, treatment involves traction for reduction followed by placement of a cervical collar. Detection after 1 month of onset usually requires surgical fusion.

An infant with suspected torticollis needs screening ultrasound to rule out hip dysplasia. DR. SKAGGS

Brief Neurologic Exam for Back Pain

Dr. Skaggs offered the following way to quickly assess children for back pain:

▸ Have the child jump up and down on one foot, then the other.

▸ Have the child walk on his or her heels with the toes pointed upward. That covers L4 for ankle dorsiflexion. “With these first two tests, you've just covered about all of the strength and balance of the lower extremities,” he said.

▸ Test the reflexes, including the umbilicus. If you lightly stroke the umbilicus on either side, the belly button should move to one side or the other. If it doesn't move, that's normal. “But if it's asymmetrical, there's a great chance there's syrinx.”

▸ Test for ankle clonus. Push up on the ball of the foot, forcibly dorsiflexing the ankle. One or two beats of clonus are normal, he said. “Three or four beats and I'd consider a neurological work-up and/or an MRI.”

▸ Assess hamstring tightness. A popliteal angle up to 30–40 degrees is normal.

▸ Check the feet. “Claw toes or a cavus foot is a sign that something neurological is going on in the spine.”

LAS VEGAS — Not long ago, physicians were taught to believe that chronic back pain does not occur in children.

“But that just isn't true,” Dr. David L. Skaggs said at meeting sponsored by the American Academy of Pediatrics' California Chapters 1, 2, 3, and 4 and the AAP.

“We did a study of kids between the ages of 11 and 14, and found that 37% of them had back pain at any given time,” said Dr. Skaggs, associate director of the Children's Orthopedic Center at Children's Hospital Los Angeles. “So when a child comes in with back pain, it can be difficult to decide what's pathologic and what's not pathologic.”

If a child presents with diffuse back pain that is triggered by physical activity, that comes and goes over time with periods of no pain, and that does not get worse at night, this is probably nothing to worry about.

Worry when a child presents with point tenderness back pain, or what he calls the “positive finger test” on physical exam. The culprit could be spondylolysis, diskitis, or a tumor.

“If the child points at one place and says, 'It hurts there,' that's when you should be concerned,” he said. “Ask, 'Does it ever hurt at night, worse enough to wake you up? Is the pain getting worse?' If they say yes, you should order a MRI of the cervicothoracic lumbar spine.”

Dr. Skaggs also discussed the following spinal problems that can occur in children:

▸ Congenital muscular torticollis. In this condition, the child's head tilts laterally with the ear toward one shoulder while the chin is rotated toward the opposite shoulder. The cause is thought to be fibrosis or compartment syndrome of the sternocleidomastoid muscle. “Oftentimes, when the kids are born they may not have this position, but within a few weeks, it develops,” Dr. Skaggs said. “That's because it takes a while for the sternocleidomastoid muscle to fibrose or develop compartment sydrome after the trauma of birth.”

If picked up early and physical therapy is begun in a timely fashion, the condition remits more than 95% of the time within the first year of life. However, most case series report about a 5% association with developmental dysplasia of the hip, “so I recommend getting a screening ultrasound in an infant who has congenital muscular torticollis. There are not enough studies to make recommendations, but I think it makes common sense,” he said.

▸ Plagiocephaly. This usually is secondary to congenital muscular torticollis. The best treatment for this is to treat the torticollis. “Encourage the child to sleep with the head tilted in the opposite position of normal, and eventually the plagiocephaly will resolve spontaneously,” he said.

If the plagiocephaly doesn't resolve in 6–8 months, referral to a neurosurgeon or an expert in bracing is warranted. “I'm generally not the biggest fan of bracing for most things in orthopedics, but [using a brace for] this really seems to work,” said Dr. Skaggs, who is also a professor of orthopedics at the University of Southern California, Los Angeles.

▸ Late-onset torticollis. In this condition, which is most commonly due to C1-C2 rotatory subluxation, the sternocleidomastoid muscle is tight on the opposite side to where the ear is toward the chin. It's in spasm from being stretched to accommodate the head position.

“Most of the time, it resolves spontaneously in a few days,” he said. “If it does not resolve in a week, that means an instant referral to a specialist in pediatric spine disorders.”

A CT scan of C1-C2 with the head turned to the right and left makes the diagnosis in most cases. If detected within 1 week, treatment involves placement of a soft cervical collar.

If detected within 1 month, treatment involves traction for reduction followed by placement of a cervical collar. Detection after 1 month of onset usually requires surgical fusion.

An infant with suspected torticollis needs screening ultrasound to rule out hip dysplasia. DR. SKAGGS

Brief Neurologic Exam for Back Pain

Dr. Skaggs offered the following way to quickly assess children for back pain:

▸ Have the child jump up and down on one foot, then the other.

▸ Have the child walk on his or her heels with the toes pointed upward. That covers L4 for ankle dorsiflexion. “With these first two tests, you've just covered about all of the strength and balance of the lower extremities,” he said.

▸ Test the reflexes, including the umbilicus. If you lightly stroke the umbilicus on either side, the belly button should move to one side or the other. If it doesn't move, that's normal. “But if it's asymmetrical, there's a great chance there's syrinx.”

▸ Test for ankle clonus. Push up on the ball of the foot, forcibly dorsiflexing the ankle. One or two beats of clonus are normal, he said. “Three or four beats and I'd consider a neurological work-up and/or an MRI.”

▸ Assess hamstring tightness. A popliteal angle up to 30–40 degrees is normal.

▸ Check the feet. “Claw toes or a cavus foot is a sign that something neurological is going on in the spine.”

LAS VEGAS — Not long ago, physicians were taught to believe that chronic back pain does not occur in children.

“But that just isn't true,” Dr. David L. Skaggs said at meeting sponsored by the American Academy of Pediatrics' California Chapters 1, 2, 3, and 4 and the AAP.

“We did a study of kids between the ages of 11 and 14, and found that 37% of them had back pain at any given time,” said Dr. Skaggs, associate director of the Children's Orthopedic Center at Children's Hospital Los Angeles. “So when a child comes in with back pain, it can be difficult to decide what's pathologic and what's not pathologic.”

If a child presents with diffuse back pain that is triggered by physical activity, that comes and goes over time with periods of no pain, and that does not get worse at night, this is probably nothing to worry about.

Worry when a child presents with point tenderness back pain, or what he calls the “positive finger test” on physical exam. The culprit could be spondylolysis, diskitis, or a tumor.

“If the child points at one place and says, 'It hurts there,' that's when you should be concerned,” he said. “Ask, 'Does it ever hurt at night, worse enough to wake you up? Is the pain getting worse?' If they say yes, you should order a MRI of the cervicothoracic lumbar spine.”

Dr. Skaggs also discussed the following spinal problems that can occur in children:

▸ Congenital muscular torticollis. In this condition, the child's head tilts laterally with the ear toward one shoulder while the chin is rotated toward the opposite shoulder. The cause is thought to be fibrosis or compartment syndrome of the sternocleidomastoid muscle. “Oftentimes, when the kids are born they may not have this position, but within a few weeks, it develops,” Dr. Skaggs said. “That's because it takes a while for the sternocleidomastoid muscle to fibrose or develop compartment sydrome after the trauma of birth.”

If picked up early and physical therapy is begun in a timely fashion, the condition remits more than 95% of the time within the first year of life. However, most case series report about a 5% association with developmental dysplasia of the hip, “so I recommend getting a screening ultrasound in an infant who has congenital muscular torticollis. There are not enough studies to make recommendations, but I think it makes common sense,” he said.

▸ Plagiocephaly. This usually is secondary to congenital muscular torticollis. The best treatment for this is to treat the torticollis. “Encourage the child to sleep with the head tilted in the opposite position of normal, and eventually the plagiocephaly will resolve spontaneously,” he said.

If the plagiocephaly doesn't resolve in 6–8 months, referral to a neurosurgeon or an expert in bracing is warranted. “I'm generally not the biggest fan of bracing for most things in orthopedics, but [using a brace for] this really seems to work,” said Dr. Skaggs, who is also a professor of orthopedics at the University of Southern California, Los Angeles.

▸ Late-onset torticollis. In this condition, which is most commonly due to C1-C2 rotatory subluxation, the sternocleidomastoid muscle is tight on the opposite side to where the ear is toward the chin. It's in spasm from being stretched to accommodate the head position.

“Most of the time, it resolves spontaneously in a few days,” he said. “If it does not resolve in a week, that means an instant referral to a specialist in pediatric spine disorders.”

A CT scan of C1-C2 with the head turned to the right and left makes the diagnosis in most cases. If detected within 1 week, treatment involves placement of a soft cervical collar.

If detected within 1 month, treatment involves traction for reduction followed by placement of a cervical collar. Detection after 1 month of onset usually requires surgical fusion.

An infant with suspected torticollis needs screening ultrasound to rule out hip dysplasia. DR. SKAGGS

Brief Neurologic Exam for Back Pain

Dr. Skaggs offered the following way to quickly assess children for back pain:

▸ Have the child jump up and down on one foot, then the other.

▸ Have the child walk on his or her heels with the toes pointed upward. That covers L4 for ankle dorsiflexion. “With these first two tests, you've just covered about all of the strength and balance of the lower extremities,” he said.

▸ Test the reflexes, including the umbilicus. If you lightly stroke the umbilicus on either side, the belly button should move to one side or the other. If it doesn't move, that's normal. “But if it's asymmetrical, there's a great chance there's syrinx.”

▸ Test for ankle clonus. Push up on the ball of the foot, forcibly dorsiflexing the ankle. One or two beats of clonus are normal, he said. “Three or four beats and I'd consider a neurological work-up and/or an MRI.”

▸ Assess hamstring tightness. A popliteal angle up to 30–40 degrees is normal.

▸ Check the feet. “Claw toes or a cavus foot is a sign that something neurological is going on in the spine.”

LAS VEGAS — A radiologist experienced with imaging the pediatric hip and spine is key to evaluation of a limping child, Dr. Melvin O. Senac Jr. advised at a meeting sponsored by the American Academy of Pediatrics' California Chapters 1, 2, 3, and 4 and the AAP.

“The imaging modalities are changing so fast, whether it's the new 64 channel CT scanners or new sequences in MRI, it's hard to really keep up,” said Dr. Senac, medical director and chief of radiology at Children's Hospital San Diego.

He discussed these causes of limping in children:

▸ Diskitis. This condition is marked by back pain, limping, inability to bear weight, and low-grade fever. It can affect infants less than 1 year old as well as teenagers.

In toddlers, nerve root irritation often causes hip pain that is worse than back pain, said Dr. Senac, who is also a professor of radiology at the University of California, San Diego. The white blood cell count is usually normal but the erythrocyte sedimentation rate is usually elevated.

Bacterial infection, usually Staphylococcus aureus, is the most common etiology of diskitis. The primary nidus is the vertebral end plate. Long-term sequelae include normal to severe kyphosis.

“One of the hallmarks of plain film findings in diskitis is narrowing of the disk space with end-plate irregularity” at L 3–4 or L 4–5. It takes 2 weeks for these findings to show on plain film. MRI shows diskitis sooner.

▸ Developmental dysplasia of the hip (DDH). The four radiographic hallmarks of this condition include a small or nonossified femoral head on the affected side, increased acetabular angle, a laterally displaced femoral head, and interruption of Shenton's line.

“The earlier you pick it up, the better that child is going to do,” Dr. Senac said. If the DDH diagnosis is made at under 6 months of age, treatment involves use of a Pavlik restraint harness to position the hip in flexion and abduction. These children “do well and they'll go on to have a normal hip,” he said.

If the diagnosis is made between ages 6 and 24 months, “those kids generally have to be hospitalized, put in traction, then taken to OR,” he said. “Then, under general anesthesia, there's an attempt at reduction. Then they're put in a cast for 6–9 months.” Delayed diagnosis and treatment result in gait problems, Dr. Senac said.

“If you pick it up in the first 6 weeks, the average stay in a harness is about 3.5 months,” he said. “If you don't make the call until 6 weeks to 3 months of age, the average stay in the harness is about 7 months. It goes up to 9 months if you diagnose it between 3 and 6 months.”

To confirm DDH, he recommends ultrasound in children younger than 4 months of age and radiographs in children aged 4 months and older. He pointed out that there is a steep learning curve to performing hip ultrasound on young infants, “so if you don't have a pediatric radiologist who does this, I suggest that the family drive somewhere to a facility that's doing a lot of these.”

▸ Transient synovitis. This is the most common nontraumatic cause of acute limp in children aged 5–10 years. The etiology is thought to be a nonspecific anti-inflammatory response of synovium to an antecedent viral or bacterial infection.

Clinical exam may reveal limp, or hip or knee pain. Affected children have low-grade fever in about 25% of cases and a mildly elevated erythrocyte sedimentation rate in 50% of cases.

“It is a diagnosis of exclusion,” Dr. Senac said. “If we do sophisticated MRI or [ultrasound], we'll find a little fluid in the joint. That's all we see.”

Radiographs are usually normal but may show a small hip effusion. Scintigraphy is more sensitive but nonspecific.

Children can expect complete recovery within a few weeks.

▸ Septic arthritis. He called this condition “the scariest thing that we have to face in this age group [aged 1–4 years] in regard to the limping child.” Affected kids experience severe pain in the involved joint, most often the hip. They usually have a fever and an elevated white blood count. On radiographs, “we're looking for widening of the joint space to see if there's evidence of a hip effusion,” Dr. Senac said.

The condition is hematogenous, “so you commonly have underlying osteomyelitis coupled with the septic joint.”

If conventional radiographs are nondiagnostic and the physical exam is equivocal, then an MRI or a radionuclide bone scan should be obtained on an urgent basis. “Time is of the essence, as the proteolytic enzymes from the hip infection can rapidly destroy cartilage and subsequently the hip joint,” he noted.

Treatment consists of draining the hip surgically and placing the child on intravenous antibiotics. If there is adjacent osteomyelitis, then this bone needs to be drained, generally by drilling.

LAS VEGAS — A radiologist experienced with imaging the pediatric hip and spine is key to evaluation of a limping child, Dr. Melvin O. Senac Jr. advised at a meeting sponsored by the American Academy of Pediatrics' California Chapters 1, 2, 3, and 4 and the AAP.

“The imaging modalities are changing so fast, whether it's the new 64 channel CT scanners or new sequences in MRI, it's hard to really keep up,” said Dr. Senac, medical director and chief of radiology at Children's Hospital San Diego.

He discussed these causes of limping in children:

▸ Diskitis. This condition is marked by back pain, limping, inability to bear weight, and low-grade fever. It can affect infants less than 1 year old as well as teenagers.

In toddlers, nerve root irritation often causes hip pain that is worse than back pain, said Dr. Senac, who is also a professor of radiology at the University of California, San Diego. The white blood cell count is usually normal but the erythrocyte sedimentation rate is usually elevated.

Bacterial infection, usually Staphylococcus aureus, is the most common etiology of diskitis. The primary nidus is the vertebral end plate. Long-term sequelae include normal to severe kyphosis.

“One of the hallmarks of plain film findings in diskitis is narrowing of the disk space with end-plate irregularity” at L 3–4 or L 4–5. It takes 2 weeks for these findings to show on plain film. MRI shows diskitis sooner.

▸ Developmental dysplasia of the hip (DDH). The four radiographic hallmarks of this condition include a small or nonossified femoral head on the affected side, increased acetabular angle, a laterally displaced femoral head, and interruption of Shenton's line.

“The earlier you pick it up, the better that child is going to do,” Dr. Senac said. If the DDH diagnosis is made at under 6 months of age, treatment involves use of a Pavlik restraint harness to position the hip in flexion and abduction. These children “do well and they'll go on to have a normal hip,” he said.

If the diagnosis is made between ages 6 and 24 months, “those kids generally have to be hospitalized, put in traction, then taken to OR,” he said. “Then, under general anesthesia, there's an attempt at reduction. Then they're put in a cast for 6–9 months.” Delayed diagnosis and treatment result in gait problems, Dr. Senac said.

“If you pick it up in the first 6 weeks, the average stay in a harness is about 3.5 months,” he said. “If you don't make the call until 6 weeks to 3 months of age, the average stay in the harness is about 7 months. It goes up to 9 months if you diagnose it between 3 and 6 months.”

To confirm DDH, he recommends ultrasound in children younger than 4 months of age and radiographs in children aged 4 months and older. He pointed out that there is a steep learning curve to performing hip ultrasound on young infants, “so if you don't have a pediatric radiologist who does this, I suggest that the family drive somewhere to a facility that's doing a lot of these.”

▸ Transient synovitis. This is the most common nontraumatic cause of acute limp in children aged 5–10 years. The etiology is thought to be a nonspecific anti-inflammatory response of synovium to an antecedent viral or bacterial infection.

Clinical exam may reveal limp, or hip or knee pain. Affected children have low-grade fever in about 25% of cases and a mildly elevated erythrocyte sedimentation rate in 50% of cases.

“It is a diagnosis of exclusion,” Dr. Senac said. “If we do sophisticated MRI or [ultrasound], we'll find a little fluid in the joint. That's all we see.”

Radiographs are usually normal but may show a small hip effusion. Scintigraphy is more sensitive but nonspecific.

Children can expect complete recovery within a few weeks.

▸ Septic arthritis. He called this condition “the scariest thing that we have to face in this age group [aged 1–4 years] in regard to the limping child.” Affected kids experience severe pain in the involved joint, most often the hip. They usually have a fever and an elevated white blood count. On radiographs, “we're looking for widening of the joint space to see if there's evidence of a hip effusion,” Dr. Senac said.

The condition is hematogenous, “so you commonly have underlying osteomyelitis coupled with the septic joint.”

If conventional radiographs are nondiagnostic and the physical exam is equivocal, then an MRI or a radionuclide bone scan should be obtained on an urgent basis. “Time is of the essence, as the proteolytic enzymes from the hip infection can rapidly destroy cartilage and subsequently the hip joint,” he noted.

Treatment consists of draining the hip surgically and placing the child on intravenous antibiotics. If there is adjacent osteomyelitis, then this bone needs to be drained, generally by drilling.

LAS VEGAS — A radiologist experienced with imaging the pediatric hip and spine is key to evaluation of a limping child, Dr. Melvin O. Senac Jr. advised at a meeting sponsored by the American Academy of Pediatrics' California Chapters 1, 2, 3, and 4 and the AAP.

“The imaging modalities are changing so fast, whether it's the new 64 channel CT scanners or new sequences in MRI, it's hard to really keep up,” said Dr. Senac, medical director and chief of radiology at Children's Hospital San Diego.

He discussed these causes of limping in children:

▸ Diskitis. This condition is marked by back pain, limping, inability to bear weight, and low-grade fever. It can affect infants less than 1 year old as well as teenagers.

In toddlers, nerve root irritation often causes hip pain that is worse than back pain, said Dr. Senac, who is also a professor of radiology at the University of California, San Diego. The white blood cell count is usually normal but the erythrocyte sedimentation rate is usually elevated.

Bacterial infection, usually Staphylococcus aureus, is the most common etiology of diskitis. The primary nidus is the vertebral end plate. Long-term sequelae include normal to severe kyphosis.

“One of the hallmarks of plain film findings in diskitis is narrowing of the disk space with end-plate irregularity” at L 3–4 or L 4–5. It takes 2 weeks for these findings to show on plain film. MRI shows diskitis sooner.

▸ Developmental dysplasia of the hip (DDH). The four radiographic hallmarks of this condition include a small or nonossified femoral head on the affected side, increased acetabular angle, a laterally displaced femoral head, and interruption of Shenton's line.

“The earlier you pick it up, the better that child is going to do,” Dr. Senac said. If the DDH diagnosis is made at under 6 months of age, treatment involves use of a Pavlik restraint harness to position the hip in flexion and abduction. These children “do well and they'll go on to have a normal hip,” he said.

If the diagnosis is made between ages 6 and 24 months, “those kids generally have to be hospitalized, put in traction, then taken to OR,” he said. “Then, under general anesthesia, there's an attempt at reduction. Then they're put in a cast for 6–9 months.” Delayed diagnosis and treatment result in gait problems, Dr. Senac said.

“If you pick it up in the first 6 weeks, the average stay in a harness is about 3.5 months,” he said. “If you don't make the call until 6 weeks to 3 months of age, the average stay in the harness is about 7 months. It goes up to 9 months if you diagnose it between 3 and 6 months.”

To confirm DDH, he recommends ultrasound in children younger than 4 months of age and radiographs in children aged 4 months and older. He pointed out that there is a steep learning curve to performing hip ultrasound on young infants, “so if you don't have a pediatric radiologist who does this, I suggest that the family drive somewhere to a facility that's doing a lot of these.”

▸ Transient synovitis. This is the most common nontraumatic cause of acute limp in children aged 5–10 years. The etiology is thought to be a nonspecific anti-inflammatory response of synovium to an antecedent viral or bacterial infection.

Clinical exam may reveal limp, or hip or knee pain. Affected children have low-grade fever in about 25% of cases and a mildly elevated erythrocyte sedimentation rate in 50% of cases.

“It is a diagnosis of exclusion,” Dr. Senac said. “If we do sophisticated MRI or [ultrasound], we'll find a little fluid in the joint. That's all we see.”

Radiographs are usually normal but may show a small hip effusion. Scintigraphy is more sensitive but nonspecific.

Children can expect complete recovery within a few weeks.

▸ Septic arthritis. He called this condition “the scariest thing that we have to face in this age group [aged 1–4 years] in regard to the limping child.” Affected kids experience severe pain in the involved joint, most often the hip. They usually have a fever and an elevated white blood count. On radiographs, “we're looking for widening of the joint space to see if there's evidence of a hip effusion,” Dr. Senac said.

The condition is hematogenous, “so you commonly have underlying osteomyelitis coupled with the septic joint.”

If conventional radiographs are nondiagnostic and the physical exam is equivocal, then an MRI or a radionuclide bone scan should be obtained on an urgent basis. “Time is of the essence, as the proteolytic enzymes from the hip infection can rapidly destroy cartilage and subsequently the hip joint,” he noted.

Treatment consists of draining the hip surgically and placing the child on intravenous antibiotics. If there is adjacent osteomyelitis, then this bone needs to be drained, generally by drilling.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).