M. Alexander Otto

MARINA DEL REY, CALIF. — Right ventricle catheterization is essential to confirm a diagnosis of pulmonary artery hypertension in patients with systemic sclerosis, according to Dr. Philip Clements, professor of medicine at the University of California, Los Angeles.

Doppler echocardiogram, which is the method used most often to diagnose pulmonary artery hypertension (PAH), is accurate to within 10 mm Hg only half the time, compared with catheterization.

More than a quarter of the time, it overestimates pulmonary artery pressure by at least 10-30 mm Hg, he said at a rheumatology seminar sponsored by the school. As a result, echocardiogram can lead to misdiagnosis and overtreatment, he said.

On top of that, it cannot distinguish between the causes of elevated pulmonary artery pressure.

In patients with systemic sclerosis, the cause of PAH is narrowed precapillary pulmonary arterioles.

In interstitial lung diseases, the cause is destruction of the pulmonary capillary bed, which elevates pressure.

And in left heart failure, a backup of blood in the pulmonary circulation elevates pressure, causing PAH, Dr. Clements said.

The different causes are treated differently.

“Can echo tell the difference?” Dr. Clements asked. “No. And before you put someone on $100,000 of medications [for PAH], it would be nice to know that the patient actually has what you're about to treat,” he said.

Right heart catheterization is moderately invasive, but in the hands of skilled cardiologists and pulmonologists, the morbidity and mortality are low.

PAH is defined on catheterization as a mean pulmonary artery pressure greater than 25 mm Hg at rest, or 30 mm Hg during exercise.

The prevalence of PAH in scleroderma patients is about 16%-20%; women and older patients are those most affected.

PAH on exercise as well as a reduction in diffusion capacity of carbon monoxide are both early indicators that PAH at rest will eventually develop.

“Left alone, it is likely to progress,” Dr. Clements said.

Whether PAH treatment makes a difference in the survival of scleroderma patients, however, is uncertain.

“The story so far is that the randomized controlled trials are short (3-4 months in duration) and done in small groups of patients. We want our patients to live for years. Unfortunately, we don't have years' worth of data,” he said.

Despite those limits, Dr. Clements said the trial findings suggest that treatment can help, especially if it comes early and involves more than one agent.

In a randomized, placebo-controlled trial that included patients with connective tissue disease, 256 subjects with PAH on long-term background intravenous epoprostenol were randomized to receive either sildenafil (20 mg t.i.d.) or placebo.

At the end of 16 weeks, the sildenafil group had a 28.8-m improvement in their 6-minute walk test distances, compared with the placebo group.

Sildenafil subjects also had greater drops in mean pulmonary arterial pressure, improvements in cardiac output, and longer time to clinical worsening. Quality of life improved as well (Ann. Intern. Med. 2008;149:521-30).

Subgroup analyses of patients who were enrolled in randomized, controlled trials with bosentan, sitaxentan (not yet approved in the United States), and treprostinil have also shown favorable effects in scleroderma PAH patients, although with lower responses than in idiopathic PAH (Eur. Respir. J. 2009;34:1219-63).

Dr. Clements believes that combination therapy is likely to evolve for scleroderma PAH, just as it has for rheumatoid arthritis, hypertension, and a host of other medical problems.

Disclosures: Dr. Clements disclosed that he is a member of Gilead Sciences Inc.'s pulmonary hypertension advisory board.

Scleroderma can affect the upper lobes of the lungs, as seen above.

Source © Bates, M.D./Custom Medical Stock Photo, Inc.

MARINA DEL REY, CALIF. — Right ventricle catheterization is essential to confirm a diagnosis of pulmonary artery hypertension in patients with systemic sclerosis, according to Dr. Philip Clements, professor of medicine at the University of California, Los Angeles.

Doppler echocardiogram, which is the method used most often to diagnose pulmonary artery hypertension (PAH), is accurate to within 10 mm Hg only half the time, compared with catheterization.

More than a quarter of the time, it overestimates pulmonary artery pressure by at least 10-30 mm Hg, he said at a rheumatology seminar sponsored by the school. As a result, echocardiogram can lead to misdiagnosis and overtreatment, he said.

On top of that, it cannot distinguish between the causes of elevated pulmonary artery pressure.

In patients with systemic sclerosis, the cause of PAH is narrowed precapillary pulmonary arterioles.

In interstitial lung diseases, the cause is destruction of the pulmonary capillary bed, which elevates pressure.

And in left heart failure, a backup of blood in the pulmonary circulation elevates pressure, causing PAH, Dr. Clements said.

The different causes are treated differently.

“Can echo tell the difference?” Dr. Clements asked. “No. And before you put someone on $100,000 of medications [for PAH], it would be nice to know that the patient actually has what you're about to treat,” he said.

Right heart catheterization is moderately invasive, but in the hands of skilled cardiologists and pulmonologists, the morbidity and mortality are low.

PAH is defined on catheterization as a mean pulmonary artery pressure greater than 25 mm Hg at rest, or 30 mm Hg during exercise.

The prevalence of PAH in scleroderma patients is about 16%-20%; women and older patients are those most affected.

PAH on exercise as well as a reduction in diffusion capacity of carbon monoxide are both early indicators that PAH at rest will eventually develop.

“Left alone, it is likely to progress,” Dr. Clements said.

Whether PAH treatment makes a difference in the survival of scleroderma patients, however, is uncertain.

“The story so far is that the randomized controlled trials are short (3-4 months in duration) and done in small groups of patients. We want our patients to live for years. Unfortunately, we don't have years' worth of data,” he said.

Despite those limits, Dr. Clements said the trial findings suggest that treatment can help, especially if it comes early and involves more than one agent.

In a randomized, placebo-controlled trial that included patients with connective tissue disease, 256 subjects with PAH on long-term background intravenous epoprostenol were randomized to receive either sildenafil (20 mg t.i.d.) or placebo.

At the end of 16 weeks, the sildenafil group had a 28.8-m improvement in their 6-minute walk test distances, compared with the placebo group.

Sildenafil subjects also had greater drops in mean pulmonary arterial pressure, improvements in cardiac output, and longer time to clinical worsening. Quality of life improved as well (Ann. Intern. Med. 2008;149:521-30).

Subgroup analyses of patients who were enrolled in randomized, controlled trials with bosentan, sitaxentan (not yet approved in the United States), and treprostinil have also shown favorable effects in scleroderma PAH patients, although with lower responses than in idiopathic PAH (Eur. Respir. J. 2009;34:1219-63).

Dr. Clements believes that combination therapy is likely to evolve for scleroderma PAH, just as it has for rheumatoid arthritis, hypertension, and a host of other medical problems.

Disclosures: Dr. Clements disclosed that he is a member of Gilead Sciences Inc.'s pulmonary hypertension advisory board.

Scleroderma can affect the upper lobes of the lungs, as seen above.

Source © Bates, M.D./Custom Medical Stock Photo, Inc.

MARINA DEL REY, CALIF. — Right ventricle catheterization is essential to confirm a diagnosis of pulmonary artery hypertension in patients with systemic sclerosis, according to Dr. Philip Clements, professor of medicine at the University of California, Los Angeles.

Doppler echocardiogram, which is the method used most often to diagnose pulmonary artery hypertension (PAH), is accurate to within 10 mm Hg only half the time, compared with catheterization.

More than a quarter of the time, it overestimates pulmonary artery pressure by at least 10-30 mm Hg, he said at a rheumatology seminar sponsored by the school. As a result, echocardiogram can lead to misdiagnosis and overtreatment, he said.

On top of that, it cannot distinguish between the causes of elevated pulmonary artery pressure.

In patients with systemic sclerosis, the cause of PAH is narrowed precapillary pulmonary arterioles.

In interstitial lung diseases, the cause is destruction of the pulmonary capillary bed, which elevates pressure.

And in left heart failure, a backup of blood in the pulmonary circulation elevates pressure, causing PAH, Dr. Clements said.

The different causes are treated differently.

“Can echo tell the difference?” Dr. Clements asked. “No. And before you put someone on $100,000 of medications [for PAH], it would be nice to know that the patient actually has what you're about to treat,” he said.

Right heart catheterization is moderately invasive, but in the hands of skilled cardiologists and pulmonologists, the morbidity and mortality are low.

PAH is defined on catheterization as a mean pulmonary artery pressure greater than 25 mm Hg at rest, or 30 mm Hg during exercise.

The prevalence of PAH in scleroderma patients is about 16%-20%; women and older patients are those most affected.

PAH on exercise as well as a reduction in diffusion capacity of carbon monoxide are both early indicators that PAH at rest will eventually develop.

“Left alone, it is likely to progress,” Dr. Clements said.

Whether PAH treatment makes a difference in the survival of scleroderma patients, however, is uncertain.

“The story so far is that the randomized controlled trials are short (3-4 months in duration) and done in small groups of patients. We want our patients to live for years. Unfortunately, we don't have years' worth of data,” he said.

Despite those limits, Dr. Clements said the trial findings suggest that treatment can help, especially if it comes early and involves more than one agent.

In a randomized, placebo-controlled trial that included patients with connective tissue disease, 256 subjects with PAH on long-term background intravenous epoprostenol were randomized to receive either sildenafil (20 mg t.i.d.) or placebo.

At the end of 16 weeks, the sildenafil group had a 28.8-m improvement in their 6-minute walk test distances, compared with the placebo group.

Sildenafil subjects also had greater drops in mean pulmonary arterial pressure, improvements in cardiac output, and longer time to clinical worsening. Quality of life improved as well (Ann. Intern. Med. 2008;149:521-30).

Subgroup analyses of patients who were enrolled in randomized, controlled trials with bosentan, sitaxentan (not yet approved in the United States), and treprostinil have also shown favorable effects in scleroderma PAH patients, although with lower responses than in idiopathic PAH (Eur. Respir. J. 2009;34:1219-63).

Dr. Clements believes that combination therapy is likely to evolve for scleroderma PAH, just as it has for rheumatoid arthritis, hypertension, and a host of other medical problems.

Disclosures: Dr. Clements disclosed that he is a member of Gilead Sciences Inc.'s pulmonary hypertension advisory board.

Scleroderma can affect the upper lobes of the lungs, as seen above.

Source © Bates, M.D./Custom Medical Stock Photo, Inc.

MARINA DEL REY, CALIF. — As the debate unfolds over both whether bisphosphonates cause femur fractures and the degree to which the benefits of drugs still outweigh the risks, a phenomenon has emerged.

Women who have taken bisphosphonates for years are being seen in doctors' offices with thigh pain that is easy to mistake for hip or knee arthritis. They have a unique constellation of radiologic findings on imaging, and they either have permanent titanium rods placed in their thigh bones or go on to full femur fractures—sometimes bilaterally—and permanent disability.

No one can yet say for sure whether they would have had those fractures regardless of bisphosphonate use, nor can anyone say if femur fractures are limited to alendronate (Fosamax) users or are a bisphosphonate class effect.

But a trend is emerging, and with it a treatment protocol.

“The thinking [among colleagues] is that this is novel and specific to bisphosphonate treatment, but only time will tell,” Dr. Benjamin C. Bengs, an orthopedic surgeon at the University of California, Los Angeles, said in an interview.

The possibility must be added to the hip pain differential in women with long-standing use of the drugs, according to Dr. Bengs and others who were interviewed for this story.

Unusual Radiology Findings

For many of the doctors who were interviewed, the question isn't so much whether bisphosphonates cause femur fractures, but rather how to care for women with a long history of using the drugs, and how to recognize signs and symptoms of impending trouble.

Any woman with pain over the thigh and those x-ray findings is definitely a candidate for prophylactic rodding, said Dr. Bengs.

The unique findings on x-ray are cortical thickening that is most pronounced on the lateral side of the femur, accompanied by a beaking lesion, also on the lateral side of the femur. Intramedullary edema is often present.

The beaking lesion is the start of a horizontal or oblique stress fracture. In time, there generally develops a “little, lucent, dark line extending from the beak to the middle of the bone,” Dr. Joseph Robinson, a radiology fellow at Cedars-Sinai Medical Center in Los Angeles, said in an interview.

“Lateral stress fractures are unusual. In our area, they are all related to bisphosphonates,” Dr. Kambiz Motamedi, a diagnostic radiologist at UCLA Medical Center.

There is a strong belief “from our sports medicine folks and rheumatologists” that there is a relationship with bisphosphonates, he said.

Both Legs Must be Examined

Standard hip x-rays don't go far enough down to detect the lesion, which is closer to the knee than the typical femur fracture would be, Dr. Robinson said.

When they do a hip series, Cedars-Sinai radiologists are careful to image lower down so they don't miss it, he said, noting that they are also putting markers on skin to identify the source of pain.

If the lesion is found, it is imperative to image the other femur as well, said Dr. Stuart L. Silverman, a rheumatologist in private practice in Beverly Hills, Calif. The other femur can go on to fracture, often within 18 months, he said in an interview.

Dr. Bengs noted that in most case, rodding is the usual treatment. It takes only a matter of weeks to recover from hip-to-knee rod placement, he said. It takes months to recover from a fracture, however, and older patients usually lose 10%-15% of their strength and ambulation during their convalescence, he added.

“The fractures are devastating,” said UCLA and Cedars-Sinai rheumatologist Dr. Solomon N. Forouzesh, who is the medical director of the rehabilitation department at Brotman Medical Center in Culver City, Calif. He said he's seen two cases in his practice.

Osteopenic Women at Risk

Active women who have osteopenia—not osteoporosis—appear to be most at risk, Dr. Nancy Lane, a University of California, Davis, rheumatologist, said in an interview.

“What I think is going on” is that bisphosphonates, by reducing bone turnover, lead to the overmineralization of cortical bone, she explained. “Over time, the bones become brittle [and] fail from too much mineralization. They cannot dissipate the load.”

It's “probably best not [to use bisphosphonates] in people with low risk of fractures who are very active,” she said.

In the past, she added, use of the drugs might have been “too aggressive.”

A Drug Holiday Is Advised

As the story unfolds, doctors are using bisphosphonates for shorter lengths of time than in the past, followed by a drug holiday and ongoing bone-density monitoring.

The risk of fracture seems to “start at about 3 years and peaks between 5 and 6 years,” Dr. Forouzesh said. To be ahead of the game, he advises not waiting until the risk peaks. “Back off ahead of time. I do a drug holiday in 3 or 4 years,” he said.

It's not clear at this point if the phenomenon—if it is truly real—is limited to alendronate or a bisphosphonate class effect.

Alendronate has been on the market the longest and has been the most widely used agent, Dr. Lane noted. “I am sure over time” it will emerge with other members of the class, as well, she said.

Meanwhile, there are efforts to raise awareness of the issue. The American College of Rheumatology issued a bulletin on the matter in March (“Atypical Femoral Fractures With Long-Term Bisphosphonate Use,” which can be accessed online at

www.rheumatology.org/publications/hotline/2010_03_22_bisphosphonate.asp

At Cedars-Sinai, “we are trying to have [a conference] to make rheumatologists and others aware of how to deal with the problem,” Dr. Robinson said.

A New Finding Unraveled, Slowly

Doctors first became aware of the issue a few years ago.

“First, there were a lot of reports in Singapore of unusual hip fractures before the lesser trochanter, [with] unusual x-ray changes,” Dr. Silverman said.

Reports started to be seen in the United States, and physicians across the country began sharing their stories.

Only by reexamining medical records did doctors realize that the patients shared a common history of bisphosphonate use, Dr. Bengs said.

At the present, it's a “slow-rolling snowball. It might be huge, but there still are doctors who do not believe it. I only converted recently because I researched it,” he said.

Many of the physicians who were interviewed for this story said they are concerned that women will go off the drugs because of press reports.

They point out that in a recent bisphosphonate manufacturer–sponsored study, investigators couldn't disprove a connection, but did conclude that the fractures are rare, and that the benefit of taking the drugs still outweighs the risks (N. Engl. J. Med. 2010;362:1761-71).

Another manufacturer-sponsored study showed that subtrochanteric femur fractures have occurred in people who have not used bisphosphonates (Osteoporos. Int. 2010;21[suppl. 1]:s7-24).

“We have a new radiologic finding, but no data that the incidence of the fractures has gone up,” Dr. Silverman said.

The Food and Drug Administration said that it is staying on top of the issue. The agency continues “to evaluate the issue of the use of bisphosphonates and atypical femur fracture,” a press person wrote in response to an e-mail inquiry.

The agency has no plans at present for an advisory committee meeting regarding the issue.

Concerned Women

As the issue continues to be examined, doctors are fielding questions from concerned women.

“My answer [to them] is that it's an unknown and unconfirmed [phenomenon], and that the data are not out there to answer the questions,” said Dr. Eric M. Ruderman of the division of rheumatology at Northwestern University in Chicago.

At present, Dr. Ruderman doesn't stop bisphosphonate use because of fracture concerns, but he does have his patients take a drug holiday after 7 years because evidence is lacking for benefit after that point, he said.

He continues monitoring bone density thereafter to assess the need for further treatment.

Disclosures: Dr. Motamedi, Dr. Robinson, and Dr. Forouzesh said that they had no conflicts to disclose. Dr. Bengs disclosed he is a paid consultant for Amgen Inc. Dr. Lane disclosed research grants, royalties, consulting fees from and positions of influence and ownership interests in Amgen, Eli Lilly & Co. and Pfizer Inc. Dr. Ruderman disclosed that he is a consultant for Amgen and Pfizer. Dr. Silverman disclosed he has served as a speaker, member of a speakers bureau, advisor for Eli Lilly, Novartis Pharmaceuticals Corp., Procter & Gamble, and Roche Inc., and that he has received research support from Eli Lilly, Procter & Gamble, Roche, and Novartis.

This femur fractured 2 days after the image revealed cortical thickening and a beaklike stress fracture, perhaps from bisphosphonates.

Source Courtesy UCLA

MARINA DEL REY, CALIF. — As the debate unfolds over both whether bisphosphonates cause femur fractures and the degree to which the benefits of drugs still outweigh the risks, a phenomenon has emerged.

Women who have taken bisphosphonates for years are being seen in doctors' offices with thigh pain that is easy to mistake for hip or knee arthritis. They have a unique constellation of radiologic findings on imaging, and they either have permanent titanium rods placed in their thigh bones or go on to full femur fractures—sometimes bilaterally—and permanent disability.

No one can yet say for sure whether they would have had those fractures regardless of bisphosphonate use, nor can anyone say if femur fractures are limited to alendronate (Fosamax) users or are a bisphosphonate class effect.

But a trend is emerging, and with it a treatment protocol.

“The thinking [among colleagues] is that this is novel and specific to bisphosphonate treatment, but only time will tell,” Dr. Benjamin C. Bengs, an orthopedic surgeon at the University of California, Los Angeles, said in an interview.

The possibility must be added to the hip pain differential in women with long-standing use of the drugs, according to Dr. Bengs and others who were interviewed for this story.

Unusual Radiology Findings

For many of the doctors who were interviewed, the question isn't so much whether bisphosphonates cause femur fractures, but rather how to care for women with a long history of using the drugs, and how to recognize signs and symptoms of impending trouble.

Any woman with pain over the thigh and those x-ray findings is definitely a candidate for prophylactic rodding, said Dr. Bengs.

The unique findings on x-ray are cortical thickening that is most pronounced on the lateral side of the femur, accompanied by a beaking lesion, also on the lateral side of the femur. Intramedullary edema is often present.

The beaking lesion is the start of a horizontal or oblique stress fracture. In time, there generally develops a “little, lucent, dark line extending from the beak to the middle of the bone,” Dr. Joseph Robinson, a radiology fellow at Cedars-Sinai Medical Center in Los Angeles, said in an interview.

“Lateral stress fractures are unusual. In our area, they are all related to bisphosphonates,” Dr. Kambiz Motamedi, a diagnostic radiologist at UCLA Medical Center.

There is a strong belief “from our sports medicine folks and rheumatologists” that there is a relationship with bisphosphonates, he said.

Both Legs Must be Examined

Standard hip x-rays don't go far enough down to detect the lesion, which is closer to the knee than the typical femur fracture would be, Dr. Robinson said.

When they do a hip series, Cedars-Sinai radiologists are careful to image lower down so they don't miss it, he said, noting that they are also putting markers on skin to identify the source of pain.

If the lesion is found, it is imperative to image the other femur as well, said Dr. Stuart L. Silverman, a rheumatologist in private practice in Beverly Hills, Calif. The other femur can go on to fracture, often within 18 months, he said in an interview.

Dr. Bengs noted that in most case, rodding is the usual treatment. It takes only a matter of weeks to recover from hip-to-knee rod placement, he said. It takes months to recover from a fracture, however, and older patients usually lose 10%-15% of their strength and ambulation during their convalescence, he added.

“The fractures are devastating,” said UCLA and Cedars-Sinai rheumatologist Dr. Solomon N. Forouzesh, who is the medical director of the rehabilitation department at Brotman Medical Center in Culver City, Calif. He said he's seen two cases in his practice.

Osteopenic Women at Risk

Active women who have osteopenia—not osteoporosis—appear to be most at risk, Dr. Nancy Lane, a University of California, Davis, rheumatologist, said in an interview.

“What I think is going on” is that bisphosphonates, by reducing bone turnover, lead to the overmineralization of cortical bone, she explained. “Over time, the bones become brittle [and] fail from too much mineralization. They cannot dissipate the load.”

It's “probably best not [to use bisphosphonates] in people with low risk of fractures who are very active,” she said.

In the past, she added, use of the drugs might have been “too aggressive.”

A Drug Holiday Is Advised

As the story unfolds, doctors are using bisphosphonates for shorter lengths of time than in the past, followed by a drug holiday and ongoing bone-density monitoring.

The risk of fracture seems to “start at about 3 years and peaks between 5 and 6 years,” Dr. Forouzesh said. To be ahead of the game, he advises not waiting until the risk peaks. “Back off ahead of time. I do a drug holiday in 3 or 4 years,” he said.

It's not clear at this point if the phenomenon—if it is truly real—is limited to alendronate or a bisphosphonate class effect.

Alendronate has been on the market the longest and has been the most widely used agent, Dr. Lane noted. “I am sure over time” it will emerge with other members of the class, as well, she said.

Meanwhile, there are efforts to raise awareness of the issue. The American College of Rheumatology issued a bulletin on the matter in March (“Atypical Femoral Fractures With Long-Term Bisphosphonate Use,” which can be accessed online at

www.rheumatology.org/publications/hotline/2010_03_22_bisphosphonate.asp

At Cedars-Sinai, “we are trying to have [a conference] to make rheumatologists and others aware of how to deal with the problem,” Dr. Robinson said.

A New Finding Unraveled, Slowly

Doctors first became aware of the issue a few years ago.

“First, there were a lot of reports in Singapore of unusual hip fractures before the lesser trochanter, [with] unusual x-ray changes,” Dr. Silverman said.

Reports started to be seen in the United States, and physicians across the country began sharing their stories.

Only by reexamining medical records did doctors realize that the patients shared a common history of bisphosphonate use, Dr. Bengs said.

At the present, it's a “slow-rolling snowball. It might be huge, but there still are doctors who do not believe it. I only converted recently because I researched it,” he said.

Many of the physicians who were interviewed for this story said they are concerned that women will go off the drugs because of press reports.

They point out that in a recent bisphosphonate manufacturer–sponsored study, investigators couldn't disprove a connection, but did conclude that the fractures are rare, and that the benefit of taking the drugs still outweighs the risks (N. Engl. J. Med. 2010;362:1761-71).

Another manufacturer-sponsored study showed that subtrochanteric femur fractures have occurred in people who have not used bisphosphonates (Osteoporos. Int. 2010;21[suppl. 1]:s7-24).

“We have a new radiologic finding, but no data that the incidence of the fractures has gone up,” Dr. Silverman said.

The Food and Drug Administration said that it is staying on top of the issue. The agency continues “to evaluate the issue of the use of bisphosphonates and atypical femur fracture,” a press person wrote in response to an e-mail inquiry.

The agency has no plans at present for an advisory committee meeting regarding the issue.

Concerned Women

As the issue continues to be examined, doctors are fielding questions from concerned women.

“My answer [to them] is that it's an unknown and unconfirmed [phenomenon], and that the data are not out there to answer the questions,” said Dr. Eric M. Ruderman of the division of rheumatology at Northwestern University in Chicago.

At present, Dr. Ruderman doesn't stop bisphosphonate use because of fracture concerns, but he does have his patients take a drug holiday after 7 years because evidence is lacking for benefit after that point, he said.

He continues monitoring bone density thereafter to assess the need for further treatment.

Disclosures: Dr. Motamedi, Dr. Robinson, and Dr. Forouzesh said that they had no conflicts to disclose. Dr. Bengs disclosed he is a paid consultant for Amgen Inc. Dr. Lane disclosed research grants, royalties, consulting fees from and positions of influence and ownership interests in Amgen, Eli Lilly & Co. and Pfizer Inc. Dr. Ruderman disclosed that he is a consultant for Amgen and Pfizer. Dr. Silverman disclosed he has served as a speaker, member of a speakers bureau, advisor for Eli Lilly, Novartis Pharmaceuticals Corp., Procter & Gamble, and Roche Inc., and that he has received research support from Eli Lilly, Procter & Gamble, Roche, and Novartis.

This femur fractured 2 days after the image revealed cortical thickening and a beaklike stress fracture, perhaps from bisphosphonates.

Source Courtesy UCLA

MARINA DEL REY, CALIF. — As the debate unfolds over both whether bisphosphonates cause femur fractures and the degree to which the benefits of drugs still outweigh the risks, a phenomenon has emerged.

Women who have taken bisphosphonates for years are being seen in doctors' offices with thigh pain that is easy to mistake for hip or knee arthritis. They have a unique constellation of radiologic findings on imaging, and they either have permanent titanium rods placed in their thigh bones or go on to full femur fractures—sometimes bilaterally—and permanent disability.

No one can yet say for sure whether they would have had those fractures regardless of bisphosphonate use, nor can anyone say if femur fractures are limited to alendronate (Fosamax) users or are a bisphosphonate class effect.

But a trend is emerging, and with it a treatment protocol.

“The thinking [among colleagues] is that this is novel and specific to bisphosphonate treatment, but only time will tell,” Dr. Benjamin C. Bengs, an orthopedic surgeon at the University of California, Los Angeles, said in an interview.

The possibility must be added to the hip pain differential in women with long-standing use of the drugs, according to Dr. Bengs and others who were interviewed for this story.

Unusual Radiology Findings

For many of the doctors who were interviewed, the question isn't so much whether bisphosphonates cause femur fractures, but rather how to care for women with a long history of using the drugs, and how to recognize signs and symptoms of impending trouble.

Any woman with pain over the thigh and those x-ray findings is definitely a candidate for prophylactic rodding, said Dr. Bengs.

The unique findings on x-ray are cortical thickening that is most pronounced on the lateral side of the femur, accompanied by a beaking lesion, also on the lateral side of the femur. Intramedullary edema is often present.

The beaking lesion is the start of a horizontal or oblique stress fracture. In time, there generally develops a “little, lucent, dark line extending from the beak to the middle of the bone,” Dr. Joseph Robinson, a radiology fellow at Cedars-Sinai Medical Center in Los Angeles, said in an interview.

“Lateral stress fractures are unusual. In our area, they are all related to bisphosphonates,” Dr. Kambiz Motamedi, a diagnostic radiologist at UCLA Medical Center.

There is a strong belief “from our sports medicine folks and rheumatologists” that there is a relationship with bisphosphonates, he said.

Both Legs Must be Examined

Standard hip x-rays don't go far enough down to detect the lesion, which is closer to the knee than the typical femur fracture would be, Dr. Robinson said.

When they do a hip series, Cedars-Sinai radiologists are careful to image lower down so they don't miss it, he said, noting that they are also putting markers on skin to identify the source of pain.

If the lesion is found, it is imperative to image the other femur as well, said Dr. Stuart L. Silverman, a rheumatologist in private practice in Beverly Hills, Calif. The other femur can go on to fracture, often within 18 months, he said in an interview.

Dr. Bengs noted that in most case, rodding is the usual treatment. It takes only a matter of weeks to recover from hip-to-knee rod placement, he said. It takes months to recover from a fracture, however, and older patients usually lose 10%-15% of their strength and ambulation during their convalescence, he added.

“The fractures are devastating,” said UCLA and Cedars-Sinai rheumatologist Dr. Solomon N. Forouzesh, who is the medical director of the rehabilitation department at Brotman Medical Center in Culver City, Calif. He said he's seen two cases in his practice.

Osteopenic Women at Risk

Active women who have osteopenia—not osteoporosis—appear to be most at risk, Dr. Nancy Lane, a University of California, Davis, rheumatologist, said in an interview.

“What I think is going on” is that bisphosphonates, by reducing bone turnover, lead to the overmineralization of cortical bone, she explained. “Over time, the bones become brittle [and] fail from too much mineralization. They cannot dissipate the load.”

It's “probably best not [to use bisphosphonates] in people with low risk of fractures who are very active,” she said.

In the past, she added, use of the drugs might have been “too aggressive.”

A Drug Holiday Is Advised

As the story unfolds, doctors are using bisphosphonates for shorter lengths of time than in the past, followed by a drug holiday and ongoing bone-density monitoring.

The risk of fracture seems to “start at about 3 years and peaks between 5 and 6 years,” Dr. Forouzesh said. To be ahead of the game, he advises not waiting until the risk peaks. “Back off ahead of time. I do a drug holiday in 3 or 4 years,” he said.

It's not clear at this point if the phenomenon—if it is truly real—is limited to alendronate or a bisphosphonate class effect.

Alendronate has been on the market the longest and has been the most widely used agent, Dr. Lane noted. “I am sure over time” it will emerge with other members of the class, as well, she said.

Meanwhile, there are efforts to raise awareness of the issue. The American College of Rheumatology issued a bulletin on the matter in March (“Atypical Femoral Fractures With Long-Term Bisphosphonate Use,” which can be accessed online at

www.rheumatology.org/publications/hotline/2010_03_22_bisphosphonate.asp

At Cedars-Sinai, “we are trying to have [a conference] to make rheumatologists and others aware of how to deal with the problem,” Dr. Robinson said.

A New Finding Unraveled, Slowly

Doctors first became aware of the issue a few years ago.

“First, there were a lot of reports in Singapore of unusual hip fractures before the lesser trochanter, [with] unusual x-ray changes,” Dr. Silverman said.

Reports started to be seen in the United States, and physicians across the country began sharing their stories.

Only by reexamining medical records did doctors realize that the patients shared a common history of bisphosphonate use, Dr. Bengs said.

At the present, it's a “slow-rolling snowball. It might be huge, but there still are doctors who do not believe it. I only converted recently because I researched it,” he said.

Many of the physicians who were interviewed for this story said they are concerned that women will go off the drugs because of press reports.

They point out that in a recent bisphosphonate manufacturer–sponsored study, investigators couldn't disprove a connection, but did conclude that the fractures are rare, and that the benefit of taking the drugs still outweighs the risks (N. Engl. J. Med. 2010;362:1761-71).

Another manufacturer-sponsored study showed that subtrochanteric femur fractures have occurred in people who have not used bisphosphonates (Osteoporos. Int. 2010;21[suppl. 1]:s7-24).

“We have a new radiologic finding, but no data that the incidence of the fractures has gone up,” Dr. Silverman said.

The Food and Drug Administration said that it is staying on top of the issue. The agency continues “to evaluate the issue of the use of bisphosphonates and atypical femur fracture,” a press person wrote in response to an e-mail inquiry.

The agency has no plans at present for an advisory committee meeting regarding the issue.

Concerned Women

As the issue continues to be examined, doctors are fielding questions from concerned women.

“My answer [to them] is that it's an unknown and unconfirmed [phenomenon], and that the data are not out there to answer the questions,” said Dr. Eric M. Ruderman of the division of rheumatology at Northwestern University in Chicago.

At present, Dr. Ruderman doesn't stop bisphosphonate use because of fracture concerns, but he does have his patients take a drug holiday after 7 years because evidence is lacking for benefit after that point, he said.

He continues monitoring bone density thereafter to assess the need for further treatment.

Disclosures: Dr. Motamedi, Dr. Robinson, and Dr. Forouzesh said that they had no conflicts to disclose. Dr. Bengs disclosed he is a paid consultant for Amgen Inc. Dr. Lane disclosed research grants, royalties, consulting fees from and positions of influence and ownership interests in Amgen, Eli Lilly & Co. and Pfizer Inc. Dr. Ruderman disclosed that he is a consultant for Amgen and Pfizer. Dr. Silverman disclosed he has served as a speaker, member of a speakers bureau, advisor for Eli Lilly, Novartis Pharmaceuticals Corp., Procter & Gamble, and Roche Inc., and that he has received research support from Eli Lilly, Procter & Gamble, Roche, and Novartis.

This femur fractured 2 days after the image revealed cortical thickening and a beaklike stress fracture, perhaps from bisphosphonates.

Source Courtesy UCLA

SEATTLE — Even without apnea, snoring, or other obvious signs of sleeping problems, sleep can be disturbed enough in children to cause attention-deficit/hyperactivity disorder–like symptoms during the day, said Dr. Maida Chen of the pediatric sleep center at Seattle Children's Hospital.

Sleep specialists have carved out a diagnostic niche called upper airways resistance syndrome (UARS) for children (and adults) who don't have overt sleep apnea and may not even snore but still can't get a good night's sleep.

The term captures the middle ground between obstructive sleep apnea and primary snoring, Dr. Chen said at the meeting. Sleep experts coined the term about 20 years ago when they realized they were missing a group of patients.

“A normal apnea-hypopnea index [during sleep studies] did not always correlate with doing okay during the day,” she said. “But people are not as aware of UARS since it is not as well quantified by research findings” as obstructive sleep apnea is.

Sleep apnea, snoring, and UARS are all different manifestations of what Dr. Chen referred to as sleep-disordered breathing. Sleep medicine isn't “just obstructive sleep apnea anymore,” she noted.

Different forms of sleep-disordered breathing share in common a narrowing of the upper airways during sleep that can be caused by enlarged adenoids and tonsils, airway inflammation, obesity, and other problems. Whatever its cause, fragmented sleep in children, as in adults, can cause daytime dysfunction.

It's important during any office visit to assess how children are functioning during the day and sleeping at night. “Less-than-optimal academic performance or behavior” is why most children are referred to the sleep clinic at Children's Hospital, Dr. Chen said.

Hyperactivity and inattention are early signs of sleep trouble in younger children. Fatigue is typically a later finding, although it can be the primary symptom of sleep apnea in older, obese kids.

Obstructive sleep apnea has been associated with hypertension, impaired growth, and other significant problems.

Abnormal overnight pulse oximetry has high predictive value for sleep apnea, but normal readings do not rule out sleep-disordered breathing, Dr. Chen said. There's less information on the effects of snoring and UARS, because they have not been studied as intensely as sleep apnea.

UARS is defined by sleep fragmentation without episodes of apnea either with or without mild gas exchange abnormalities. Most UARS kids snore, but not all do; they may just breathe loudly or through their mouths. Nasal airflow tends to be abnormal, as well.

But the syndrome is still being defined. “We need more research,” Dr. Chen said. “Snoring is abnormal in every circumstance,” and signals upper airway resistance at some level, he said. Snoring falls within the spectrum of sleep-disordered breathing if it is present more than 3 nights a week for more than a month.

An overnight polysomnogram is the preferred method for diagnosing sleep issues, Dr. Chen said. Brain waves, airflow, breathing effort measures, number of apneic episodes per hour, and movement are among the things monitored.

Treatment depends on cause. In most children, adenotonsillectomy resolves obstructive sleep apnea and, presumably, UARS and snoring in children, she said. Treating underlying airway inflammation can help, too.

Sleeping inclined or on the side can help in mild cases. A tennis ball can even be taped to the back of a child's pajama top to keep the child from sleeping on his or her back, which makes symptoms worse.

Positive airway pressure is another option. It is most commonly used—along with inclined sleeping—in obese children and children with underlying medical conditions, and when adenotonsillectomy fails to fix nighttime breathing issues.

Sometimes children will grow out of the problem; as they grow, so do their upper airways.

Disclosures: None were reported.

SEATTLE — Even without apnea, snoring, or other obvious signs of sleeping problems, sleep can be disturbed enough in children to cause attention-deficit/hyperactivity disorder–like symptoms during the day, said Dr. Maida Chen of the pediatric sleep center at Seattle Children's Hospital.

Sleep specialists have carved out a diagnostic niche called upper airways resistance syndrome (UARS) for children (and adults) who don't have overt sleep apnea and may not even snore but still can't get a good night's sleep.

The term captures the middle ground between obstructive sleep apnea and primary snoring, Dr. Chen said at the meeting. Sleep experts coined the term about 20 years ago when they realized they were missing a group of patients.

“A normal apnea-hypopnea index [during sleep studies] did not always correlate with doing okay during the day,” she said. “But people are not as aware of UARS since it is not as well quantified by research findings” as obstructive sleep apnea is.

Sleep apnea, snoring, and UARS are all different manifestations of what Dr. Chen referred to as sleep-disordered breathing. Sleep medicine isn't “just obstructive sleep apnea anymore,” she noted.

Different forms of sleep-disordered breathing share in common a narrowing of the upper airways during sleep that can be caused by enlarged adenoids and tonsils, airway inflammation, obesity, and other problems. Whatever its cause, fragmented sleep in children, as in adults, can cause daytime dysfunction.

It's important during any office visit to assess how children are functioning during the day and sleeping at night. “Less-than-optimal academic performance or behavior” is why most children are referred to the sleep clinic at Children's Hospital, Dr. Chen said.

Hyperactivity and inattention are early signs of sleep trouble in younger children. Fatigue is typically a later finding, although it can be the primary symptom of sleep apnea in older, obese kids.

Obstructive sleep apnea has been associated with hypertension, impaired growth, and other significant problems.

Abnormal overnight pulse oximetry has high predictive value for sleep apnea, but normal readings do not rule out sleep-disordered breathing, Dr. Chen said. There's less information on the effects of snoring and UARS, because they have not been studied as intensely as sleep apnea.

UARS is defined by sleep fragmentation without episodes of apnea either with or without mild gas exchange abnormalities. Most UARS kids snore, but not all do; they may just breathe loudly or through their mouths. Nasal airflow tends to be abnormal, as well.

But the syndrome is still being defined. “We need more research,” Dr. Chen said. “Snoring is abnormal in every circumstance,” and signals upper airway resistance at some level, he said. Snoring falls within the spectrum of sleep-disordered breathing if it is present more than 3 nights a week for more than a month.

An overnight polysomnogram is the preferred method for diagnosing sleep issues, Dr. Chen said. Brain waves, airflow, breathing effort measures, number of apneic episodes per hour, and movement are among the things monitored.

Treatment depends on cause. In most children, adenotonsillectomy resolves obstructive sleep apnea and, presumably, UARS and snoring in children, she said. Treating underlying airway inflammation can help, too.

Sleeping inclined or on the side can help in mild cases. A tennis ball can even be taped to the back of a child's pajama top to keep the child from sleeping on his or her back, which makes symptoms worse.

Positive airway pressure is another option. It is most commonly used—along with inclined sleeping—in obese children and children with underlying medical conditions, and when adenotonsillectomy fails to fix nighttime breathing issues.

Sometimes children will grow out of the problem; as they grow, so do their upper airways.

Disclosures: None were reported.

SEATTLE — Even without apnea, snoring, or other obvious signs of sleeping problems, sleep can be disturbed enough in children to cause attention-deficit/hyperactivity disorder–like symptoms during the day, said Dr. Maida Chen of the pediatric sleep center at Seattle Children's Hospital.

Sleep specialists have carved out a diagnostic niche called upper airways resistance syndrome (UARS) for children (and adults) who don't have overt sleep apnea and may not even snore but still can't get a good night's sleep.

The term captures the middle ground between obstructive sleep apnea and primary snoring, Dr. Chen said at the meeting. Sleep experts coined the term about 20 years ago when they realized they were missing a group of patients.

“A normal apnea-hypopnea index [during sleep studies] did not always correlate with doing okay during the day,” she said. “But people are not as aware of UARS since it is not as well quantified by research findings” as obstructive sleep apnea is.

Sleep apnea, snoring, and UARS are all different manifestations of what Dr. Chen referred to as sleep-disordered breathing. Sleep medicine isn't “just obstructive sleep apnea anymore,” she noted.

Different forms of sleep-disordered breathing share in common a narrowing of the upper airways during sleep that can be caused by enlarged adenoids and tonsils, airway inflammation, obesity, and other problems. Whatever its cause, fragmented sleep in children, as in adults, can cause daytime dysfunction.

It's important during any office visit to assess how children are functioning during the day and sleeping at night. “Less-than-optimal academic performance or behavior” is why most children are referred to the sleep clinic at Children's Hospital, Dr. Chen said.

Hyperactivity and inattention are early signs of sleep trouble in younger children. Fatigue is typically a later finding, although it can be the primary symptom of sleep apnea in older, obese kids.

Obstructive sleep apnea has been associated with hypertension, impaired growth, and other significant problems.

Abnormal overnight pulse oximetry has high predictive value for sleep apnea, but normal readings do not rule out sleep-disordered breathing, Dr. Chen said. There's less information on the effects of snoring and UARS, because they have not been studied as intensely as sleep apnea.

UARS is defined by sleep fragmentation without episodes of apnea either with or without mild gas exchange abnormalities. Most UARS kids snore, but not all do; they may just breathe loudly or through their mouths. Nasal airflow tends to be abnormal, as well.

But the syndrome is still being defined. “We need more research,” Dr. Chen said. “Snoring is abnormal in every circumstance,” and signals upper airway resistance at some level, he said. Snoring falls within the spectrum of sleep-disordered breathing if it is present more than 3 nights a week for more than a month.

An overnight polysomnogram is the preferred method for diagnosing sleep issues, Dr. Chen said. Brain waves, airflow, breathing effort measures, number of apneic episodes per hour, and movement are among the things monitored.

Treatment depends on cause. In most children, adenotonsillectomy resolves obstructive sleep apnea and, presumably, UARS and snoring in children, she said. Treating underlying airway inflammation can help, too.

Sleeping inclined or on the side can help in mild cases. A tennis ball can even be taped to the back of a child's pajama top to keep the child from sleeping on his or her back, which makes symptoms worse.

Positive airway pressure is another option. It is most commonly used—along with inclined sleeping—in obese children and children with underlying medical conditions, and when adenotonsillectomy fails to fix nighttime breathing issues.

Sometimes children will grow out of the problem; as they grow, so do their upper airways.

Disclosures: None were reported.

SEATTLE — Take-home, ambulatory blood pressure monitors for children ensure more accurate blood pressure assessments and rule out white-coat hypertension, nephrologists at Seattle Children's Hospital's hypertension clinic have found.

The clinic ruled out white-coat hypertension in about 30%–40% of the roughly 200 children sent home with the monitors in 2009, according to Dr. Jodi Smith of the clinic.

Although more expensive than an office blood pressure reading, “if used as first-line, before doing a bunch of other diagnostic tests, it can decrease costs” overall, Dr. Smith said at a conference sponsored by the North Pacific Pediatric Society.

The clinic uses ambulatory monitors made by SpaceLabs Medical, Inc., of Issaquah, Wash. They cost about $3,000 each.

Dr. Smith, along with her nephrologist colleagues, sees patients in the hospital's hypertension clinic due to the correlation of pediatric hypertension and renal problems. The hypertension clinic started using the monitors about a year ago, switching from office readings and automated blood pressure cuffs that caretakers used to take a few measurements a day at home.

The units consist of a blood pressure cuff and an iPod-sized monitor that is worn around the waist and easily concealed under a sweatshirt. The cuffs inflate every 20–30 minutes for 24 hours. Older children adapt well to the frequent squeezes, Dr. Smith said, but the approach would not be appropriate for children under age 7.

The read-outs go far beyond a listing of systolic and diastolic pressures, and are complicated to interpret, she said. “They look for patterns,” including blood pressure load, and the presence—or not—of a normal drop in blood pressure at night.

Children also keep an activity log, so a spike in blood pressure during a soccer game, for instance, isn't misinterpreted.

It's a first-line assessment at the clinic, especially to confirm hypertension in otherwise healthy children.

Schedulers get prior insurance authorization for an ambulatory monitor before the child comes in, so they can be sent home with one after the first visit.

Her clinic matches readings to a chart in the National Heart, Lung, and Blood Institute's Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Pediatrics 2004;114:555-76).

“We get calls all the time [from pediatricians wondering] what's normal and what's not,” she said. “Normals change through childhood. It is hard to define what level is dangerous.”

The chart helps. At her clinic, blood pressures at or above the 90th percentile trigger intervention. Kids who fall between the 90th and 94th percentile are considered pre-hypertensive, the point at which lifestyle changes are initiated along with medication if there are comorbidities.

At or above the 95th percentile, children are deemed hypertensive. Treatment and drug selection depends on cause, symptoms, the presence of end-organ damage or diabetes, and other considerations.

With increasing rates of obesity, primary hypertension is on the rise in the pediatric population, but hypertensive children are still more likely than adults to have definable causes for the condition.

Renal problems are most likely, followed by renovascular, endocrine, and genetic problems, Dr. Smith said.

Although rare, post-streptococcal glomerulonephritis is the most common cause of acute glomerulonephritis in kids. Other causes of acute nephritis, with more uncertain outcomes—lupus, bacterial endocarditis, shunt nephritis, membranoproliferative glomerulonephritis—will typically depress both C3 and C4.

IgA nephropathy and Henoch-Schnlein purpura nephritis are associated with normal C3 and C4, said Dr. Smith, who had no conflicts of interest to report.

SEATTLE — Take-home, ambulatory blood pressure monitors for children ensure more accurate blood pressure assessments and rule out white-coat hypertension, nephrologists at Seattle Children's Hospital's hypertension clinic have found.

The clinic ruled out white-coat hypertension in about 30%–40% of the roughly 200 children sent home with the monitors in 2009, according to Dr. Jodi Smith of the clinic.

Although more expensive than an office blood pressure reading, “if used as first-line, before doing a bunch of other diagnostic tests, it can decrease costs” overall, Dr. Smith said at a conference sponsored by the North Pacific Pediatric Society.

The clinic uses ambulatory monitors made by SpaceLabs Medical, Inc., of Issaquah, Wash. They cost about $3,000 each.

Dr. Smith, along with her nephrologist colleagues, sees patients in the hospital's hypertension clinic due to the correlation of pediatric hypertension and renal problems. The hypertension clinic started using the monitors about a year ago, switching from office readings and automated blood pressure cuffs that caretakers used to take a few measurements a day at home.

The units consist of a blood pressure cuff and an iPod-sized monitor that is worn around the waist and easily concealed under a sweatshirt. The cuffs inflate every 20–30 minutes for 24 hours. Older children adapt well to the frequent squeezes, Dr. Smith said, but the approach would not be appropriate for children under age 7.

The read-outs go far beyond a listing of systolic and diastolic pressures, and are complicated to interpret, she said. “They look for patterns,” including blood pressure load, and the presence—or not—of a normal drop in blood pressure at night.

Children also keep an activity log, so a spike in blood pressure during a soccer game, for instance, isn't misinterpreted.

It's a first-line assessment at the clinic, especially to confirm hypertension in otherwise healthy children.

Schedulers get prior insurance authorization for an ambulatory monitor before the child comes in, so they can be sent home with one after the first visit.

Her clinic matches readings to a chart in the National Heart, Lung, and Blood Institute's Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Pediatrics 2004;114:555-76).

“We get calls all the time [from pediatricians wondering] what's normal and what's not,” she said. “Normals change through childhood. It is hard to define what level is dangerous.”

The chart helps. At her clinic, blood pressures at or above the 90th percentile trigger intervention. Kids who fall between the 90th and 94th percentile are considered pre-hypertensive, the point at which lifestyle changes are initiated along with medication if there are comorbidities.

At or above the 95th percentile, children are deemed hypertensive. Treatment and drug selection depends on cause, symptoms, the presence of end-organ damage or diabetes, and other considerations.

With increasing rates of obesity, primary hypertension is on the rise in the pediatric population, but hypertensive children are still more likely than adults to have definable causes for the condition.

Renal problems are most likely, followed by renovascular, endocrine, and genetic problems, Dr. Smith said.

Although rare, post-streptococcal glomerulonephritis is the most common cause of acute glomerulonephritis in kids. Other causes of acute nephritis, with more uncertain outcomes—lupus, bacterial endocarditis, shunt nephritis, membranoproliferative glomerulonephritis—will typically depress both C3 and C4.

IgA nephropathy and Henoch-Schnlein purpura nephritis are associated with normal C3 and C4, said Dr. Smith, who had no conflicts of interest to report.

SEATTLE — Take-home, ambulatory blood pressure monitors for children ensure more accurate blood pressure assessments and rule out white-coat hypertension, nephrologists at Seattle Children's Hospital's hypertension clinic have found.

The clinic ruled out white-coat hypertension in about 30%–40% of the roughly 200 children sent home with the monitors in 2009, according to Dr. Jodi Smith of the clinic.

Although more expensive than an office blood pressure reading, “if used as first-line, before doing a bunch of other diagnostic tests, it can decrease costs” overall, Dr. Smith said at a conference sponsored by the North Pacific Pediatric Society.

The clinic uses ambulatory monitors made by SpaceLabs Medical, Inc., of Issaquah, Wash. They cost about $3,000 each.

Dr. Smith, along with her nephrologist colleagues, sees patients in the hospital's hypertension clinic due to the correlation of pediatric hypertension and renal problems. The hypertension clinic started using the monitors about a year ago, switching from office readings and automated blood pressure cuffs that caretakers used to take a few measurements a day at home.

The units consist of a blood pressure cuff and an iPod-sized monitor that is worn around the waist and easily concealed under a sweatshirt. The cuffs inflate every 20–30 minutes for 24 hours. Older children adapt well to the frequent squeezes, Dr. Smith said, but the approach would not be appropriate for children under age 7.

The read-outs go far beyond a listing of systolic and diastolic pressures, and are complicated to interpret, she said. “They look for patterns,” including blood pressure load, and the presence—or not—of a normal drop in blood pressure at night.

Children also keep an activity log, so a spike in blood pressure during a soccer game, for instance, isn't misinterpreted.

It's a first-line assessment at the clinic, especially to confirm hypertension in otherwise healthy children.

Schedulers get prior insurance authorization for an ambulatory monitor before the child comes in, so they can be sent home with one after the first visit.

Her clinic matches readings to a chart in the National Heart, Lung, and Blood Institute's Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Pediatrics 2004;114:555-76).

“We get calls all the time [from pediatricians wondering] what's normal and what's not,” she said. “Normals change through childhood. It is hard to define what level is dangerous.”

The chart helps. At her clinic, blood pressures at or above the 90th percentile trigger intervention. Kids who fall between the 90th and 94th percentile are considered pre-hypertensive, the point at which lifestyle changes are initiated along with medication if there are comorbidities.

At or above the 95th percentile, children are deemed hypertensive. Treatment and drug selection depends on cause, symptoms, the presence of end-organ damage or diabetes, and other considerations.

With increasing rates of obesity, primary hypertension is on the rise in the pediatric population, but hypertensive children are still more likely than adults to have definable causes for the condition.

Renal problems are most likely, followed by renovascular, endocrine, and genetic problems, Dr. Smith said.

Although rare, post-streptococcal glomerulonephritis is the most common cause of acute glomerulonephritis in kids. Other causes of acute nephritis, with more uncertain outcomes—lupus, bacterial endocarditis, shunt nephritis, membranoproliferative glomerulonephritis—will typically depress both C3 and C4.

IgA nephropathy and Henoch-Schnlein purpura nephritis are associated with normal C3 and C4, said Dr. Smith, who had no conflicts of interest to report.

SEATTLE — Proton-pump inhibitors are often the wrong choice when it comes to treating abdominal pain in children, according to Dr. Ghassan Wahbeh.

Dr. Wahbeh, director of the inflammatory bowel disease program at Seattle Children's Hospital, sees many children referred to him with gastrointestinal complaints who are on proton-pump inhibitors (PPIs) when they are not indicated. He suspects the drugs are overused.

Some PPIs are indicated for Helicobacter pylori–related gastric complications and pediatric gastroesophageal reflux disease (GERD), which has a definable triad of symptoms—chest pain, heartburn, and dysphagia—but Dr. Wahbeh said patients with abdominal pain come to him on PPIs even though they have none of those classic GERD symptoms or evidence of H. pylori infections.

On work-up, those children most often turn out to have functional constipation and functional abdominal pain, both of which are underrecognized, Dr. Wahbeh said at a conference sponsored by the North Pacific Pediatric Society.

The pain is thought to be related to gastrointestinal nerve inflammation and hypersensitivity, triggered by infection, medication reaction, or some other insult. Constipation can make it worse. The two often go together, he said.

Pain location in constipated children varies. When it's epigastric pain, it's often incorrectly presumed to be GERD related. “Epigastric pain does not mean gastroesophageal reflux. The presumed relation of epigastric pain to gastroesophageal reflux is unproven,” Dr. Wahbeh said.

“It is possible that severe reflux esophagitis with ulceration can cause upper abdominal pain. However, this is quite rarely seen in clinical practice, and if so, quite specific to children with neuromuscular disorders [such as] cerebral palsy or large diaphragmatic hernias,” he said.

But “we are harpooned by ads for acid blocker. They are imbedded in mind,” he said, so they are turned to a bit too often.

Although PPIs may have a temporary laxative effect, their use otherwise in functional abdominal pain and constipation is problematic, he said.

A month of treatment with a branded PPI can run $500, he said. Once the drug is stopped, there's the risk of oversecretion of stomach acid (Gastroenterology 2009;137:80-7).

Also, incorrectly labeling a child with a pre-existing condition like GERD can cause problems with insurance coverage later on and trap a child into an algorithm of GERD treatments.

When working up a child with suspected functional constipation and abdominal pain, a blood panel makes sense to rule out anemia, hypoalbuminemia, celiac disease, inflammatory markers, and other problems, and also to calm the nerves of patients and families. Imaging will help rule out gallstones, abdominal masses, and anatomic abnormalities, if symptoms warrant it, Dr. Wahbeh said.

Along with a comprehensive history and physical, a digital rectal exam is essential. It is the only effective and accurate way to determine if a child is constipated, but “it's not comfortable, and it's not something most of us jump at,” he said. However, if its importance is explained to patients and caretakers, it's “rarely turned down,” he added. Having a medical assistant or nurse chaperone present during the digital exam will help avoid problems in case the exam is misinterpreted by patients and families.

Functional abdominal pain and constipation can be a frustrating diagnosis for clinicians, caretakers, and children alike. It seems strange to patients and families that such severe and long-lasting pain can be caused by something as common as constipation, or made worse by fructose or lactose intolerance.

Adding to the frustration, treatment is conservative and improvements are slow in coming. Depression and anxiety during the process are not uncommon, Dr. Wahbeh said.

Because of that, he said it is essential to establish trust in the therapeutic relationship. Tell patients and caretakers that things will “get better, but not any time soon,” and that it will take a multidisciplinary approach that sometimes includes a psychologist, social worker, pain specialist, and dietician, among others, he said.

In addition to diet modifications and other interventions, a child with functional constipation will be on daily laxatives, sometimes for over a year. Biofeedback and exercise also help, and there's some support in the literature for gabapentin, amitriptyline, or clonidine to help with the presumed nerve inflammation and hypersensitivity, Dr. Wahbeh said.

Dr. Wahbeh disclosed research or grant support from Abbott Laboratories, Centocor Inc., and UCB.

SEATTLE — Proton-pump inhibitors are often the wrong choice when it comes to treating abdominal pain in children, according to Dr. Ghassan Wahbeh.

Dr. Wahbeh, director of the inflammatory bowel disease program at Seattle Children's Hospital, sees many children referred to him with gastrointestinal complaints who are on proton-pump inhibitors (PPIs) when they are not indicated. He suspects the drugs are overused.

Some PPIs are indicated for Helicobacter pylori–related gastric complications and pediatric gastroesophageal reflux disease (GERD), which has a definable triad of symptoms—chest pain, heartburn, and dysphagia—but Dr. Wahbeh said patients with abdominal pain come to him on PPIs even though they have none of those classic GERD symptoms or evidence of H. pylori infections.

On work-up, those children most often turn out to have functional constipation and functional abdominal pain, both of which are underrecognized, Dr. Wahbeh said at a conference sponsored by the North Pacific Pediatric Society.

The pain is thought to be related to gastrointestinal nerve inflammation and hypersensitivity, triggered by infection, medication reaction, or some other insult. Constipation can make it worse. The two often go together, he said.

Pain location in constipated children varies. When it's epigastric pain, it's often incorrectly presumed to be GERD related. “Epigastric pain does not mean gastroesophageal reflux. The presumed relation of epigastric pain to gastroesophageal reflux is unproven,” Dr. Wahbeh said.

“It is possible that severe reflux esophagitis with ulceration can cause upper abdominal pain. However, this is quite rarely seen in clinical practice, and if so, quite specific to children with neuromuscular disorders [such as] cerebral palsy or large diaphragmatic hernias,” he said.

But “we are harpooned by ads for acid blocker. They are imbedded in mind,” he said, so they are turned to a bit too often.

Although PPIs may have a temporary laxative effect, their use otherwise in functional abdominal pain and constipation is problematic, he said.

A month of treatment with a branded PPI can run $500, he said. Once the drug is stopped, there's the risk of oversecretion of stomach acid (Gastroenterology 2009;137:80-7).

Also, incorrectly labeling a child with a pre-existing condition like GERD can cause problems with insurance coverage later on and trap a child into an algorithm of GERD treatments.

When working up a child with suspected functional constipation and abdominal pain, a blood panel makes sense to rule out anemia, hypoalbuminemia, celiac disease, inflammatory markers, and other problems, and also to calm the nerves of patients and families. Imaging will help rule out gallstones, abdominal masses, and anatomic abnormalities, if symptoms warrant it, Dr. Wahbeh said.

Along with a comprehensive history and physical, a digital rectal exam is essential. It is the only effective and accurate way to determine if a child is constipated, but “it's not comfortable, and it's not something most of us jump at,” he said. However, if its importance is explained to patients and caretakers, it's “rarely turned down,” he added. Having a medical assistant or nurse chaperone present during the digital exam will help avoid problems in case the exam is misinterpreted by patients and families.

Functional abdominal pain and constipation can be a frustrating diagnosis for clinicians, caretakers, and children alike. It seems strange to patients and families that such severe and long-lasting pain can be caused by something as common as constipation, or made worse by fructose or lactose intolerance.

Adding to the frustration, treatment is conservative and improvements are slow in coming. Depression and anxiety during the process are not uncommon, Dr. Wahbeh said.

Because of that, he said it is essential to establish trust in the therapeutic relationship. Tell patients and caretakers that things will “get better, but not any time soon,” and that it will take a multidisciplinary approach that sometimes includes a psychologist, social worker, pain specialist, and dietician, among others, he said.

In addition to diet modifications and other interventions, a child with functional constipation will be on daily laxatives, sometimes for over a year. Biofeedback and exercise also help, and there's some support in the literature for gabapentin, amitriptyline, or clonidine to help with the presumed nerve inflammation and hypersensitivity, Dr. Wahbeh said.

Dr. Wahbeh disclosed research or grant support from Abbott Laboratories, Centocor Inc., and UCB.

SEATTLE — Proton-pump inhibitors are often the wrong choice when it comes to treating abdominal pain in children, according to Dr. Ghassan Wahbeh.

Dr. Wahbeh, director of the inflammatory bowel disease program at Seattle Children's Hospital, sees many children referred to him with gastrointestinal complaints who are on proton-pump inhibitors (PPIs) when they are not indicated. He suspects the drugs are overused.

Some PPIs are indicated for Helicobacter pylori–related gastric complications and pediatric gastroesophageal reflux disease (GERD), which has a definable triad of symptoms—chest pain, heartburn, and dysphagia—but Dr. Wahbeh said patients with abdominal pain come to him on PPIs even though they have none of those classic GERD symptoms or evidence of H. pylori infections.

On work-up, those children most often turn out to have functional constipation and functional abdominal pain, both of which are underrecognized, Dr. Wahbeh said at a conference sponsored by the North Pacific Pediatric Society.

The pain is thought to be related to gastrointestinal nerve inflammation and hypersensitivity, triggered by infection, medication reaction, or some other insult. Constipation can make it worse. The two often go together, he said.

Pain location in constipated children varies. When it's epigastric pain, it's often incorrectly presumed to be GERD related. “Epigastric pain does not mean gastroesophageal reflux. The presumed relation of epigastric pain to gastroesophageal reflux is unproven,” Dr. Wahbeh said.

“It is possible that severe reflux esophagitis with ulceration can cause upper abdominal pain. However, this is quite rarely seen in clinical practice, and if so, quite specific to children with neuromuscular disorders [such as] cerebral palsy or large diaphragmatic hernias,” he said.

But “we are harpooned by ads for acid blocker. They are imbedded in mind,” he said, so they are turned to a bit too often.

Although PPIs may have a temporary laxative effect, their use otherwise in functional abdominal pain and constipation is problematic, he said.

A month of treatment with a branded PPI can run $500, he said. Once the drug is stopped, there's the risk of oversecretion of stomach acid (Gastroenterology 2009;137:80-7).

Also, incorrectly labeling a child with a pre-existing condition like GERD can cause problems with insurance coverage later on and trap a child into an algorithm of GERD treatments.

When working up a child with suspected functional constipation and abdominal pain, a blood panel makes sense to rule out anemia, hypoalbuminemia, celiac disease, inflammatory markers, and other problems, and also to calm the nerves of patients and families. Imaging will help rule out gallstones, abdominal masses, and anatomic abnormalities, if symptoms warrant it, Dr. Wahbeh said.

Along with a comprehensive history and physical, a digital rectal exam is essential. It is the only effective and accurate way to determine if a child is constipated, but “it's not comfortable, and it's not something most of us jump at,” he said. However, if its importance is explained to patients and caretakers, it's “rarely turned down,” he added. Having a medical assistant or nurse chaperone present during the digital exam will help avoid problems in case the exam is misinterpreted by patients and families.

Functional abdominal pain and constipation can be a frustrating diagnosis for clinicians, caretakers, and children alike. It seems strange to patients and families that such severe and long-lasting pain can be caused by something as common as constipation, or made worse by fructose or lactose intolerance.

Adding to the frustration, treatment is conservative and improvements are slow in coming. Depression and anxiety during the process are not uncommon, Dr. Wahbeh said.

Because of that, he said it is essential to establish trust in the therapeutic relationship. Tell patients and caretakers that things will “get better, but not any time soon,” and that it will take a multidisciplinary approach that sometimes includes a psychologist, social worker, pain specialist, and dietician, among others, he said.

In addition to diet modifications and other interventions, a child with functional constipation will be on daily laxatives, sometimes for over a year. Biofeedback and exercise also help, and there's some support in the literature for gabapentin, amitriptyline, or clonidine to help with the presumed nerve inflammation and hypersensitivity, Dr. Wahbeh said.

Dr. Wahbeh disclosed research or grant support from Abbott Laboratories, Centocor Inc., and UCB.

SEATTLE — If an infant fails a hearing test, think cytomegalovirus infection, advised Dr. Kathleen Sie.

Congenital cytomegalovirus (CMV) infection is now known to be the leading nongenetic cause of deafness in children, said Dr. Sie, clinical director of Seattle Children's Hospital's childhood communication center.

In infants with nongenetic hearing loss—at least 25% of cases—she recommended doing cytomegalovirus (CMV) screening by shell vial urine culture if the infant is within the first 6 weeks of life. Past that, the diagnosis must be made by polymerase chain reaction (PCR) testing of the neonatal blood spot.

If an infant is positive for CMV, treatment with valganciclovir, an oral antiviral agent, might halt or reverse hearing loss, Dr. Sie said at a conference sponsored by the North Pacific Pediatric Society.

Although not the standard of practice now, she said screening and treatment for pediatric CMV-related hearing loss will become increasingly common over the next 10 years. CMV will become the treatable cause of hearing loss in children because of promising results from small, early studies and because of the availability of valganciclovir, the active metabolite of ganciclovir, the drug used in those early studies.

In a small, randomized clinical trial published in 2003, the hearing of 25 infants born with symptomatic CMV infections and treated with ganciclovir did not deteriorate by 6 months; hearing deteriorated in 41% (7 of 17) of untreated infants. At or beyond age 1 year, hearing deteriorated in 21% (5 of 24) of ganciclovir-treated patients, compared with 68% (13 of 19) of controls (J. Pediatr. 2003;143:16-25).

The study did not lead to widespread use of ganciclovir for CMV hearing loss, however, because the results came only after the drug was given for 6 weeks through a central line, and because 63% of those treated developed grade 3 or 4 neutropenia.

Drug administration drawbacks, at least, will be avoided with the oral agent valganciclovir, she said.

An ongoing National Institutes of Health–funded study could shed light on the use of the drug; a 6-week course of valganciclovir is being tested against a 6-month course for CMV-related hearing loss and developmental delays.

About 1% of newborns are born with congenital CMV infections in Washington state, Dr. Sie noted. Nationwide, National Institutes of Health estimates range from 0.5% to 1.5%.

Between 22% and 65% will have hearing loss if they are born with CMV symptoms; the percentage is 6%-23%, if the infants are born asymptomatic (J. Clin. Virol. 2006;35:226-31).

CMV hearing loss can be either unilateral or bilateral, and vary in the severity and frequencies affected, Dr. Sie said. It is unclear how the virus damages hearing, but CMV has been detected in the perilymphatic spaces of the inner ear and the spiral ganglion, the location of the nerve endings in the inner ear.

The reason shell vial urine cultures can be done at or before 6 weeks of age is that an infected newborn will likely be shedding virus. Later, a neonatal blood spot PCR must be done to rule out postnatal infection, which is not thought to carry the same risk of hearing loss.

Although infants with hearing loss are not yet typically screened and treated for CMV, when they are, treatment is usually initiated only when the infection is caught by 6 months of age, Dr. Sie said. That misses later-onset CMV hearing loss.

Dr. Sie said he expects that in coming years, treatment will be initiated even if the diagnosis comes later. “We do know that [CMV-related] damage can continue for the first few years of life. So it's reasonable to think the window for treatment might extend beyond 6 months,” she said.

Disclosures: Dr. Sie reported that she had no conflicts of interest to disclose.

SEATTLE — If an infant fails a hearing test, think cytomegalovirus infection, advised Dr. Kathleen Sie.

Congenital cytomegalovirus (CMV) infection is now known to be the leading nongenetic cause of deafness in children, said Dr. Sie, clinical director of Seattle Children's Hospital's childhood communication center.

In infants with nongenetic hearing loss—at least 25% of cases—she recommended doing cytomegalovirus (CMV) screening by shell vial urine culture if the infant is within the first 6 weeks of life. Past that, the diagnosis must be made by polymerase chain reaction (PCR) testing of the neonatal blood spot.

If an infant is positive for CMV, treatment with valganciclovir, an oral antiviral agent, might halt or reverse hearing loss, Dr. Sie said at a conference sponsored by the North Pacific Pediatric Society.

Although not the standard of practice now, she said screening and treatment for pediatric CMV-related hearing loss will become increasingly common over the next 10 years. CMV will become the treatable cause of hearing loss in children because of promising results from small, early studies and because of the availability of valganciclovir, the active metabolite of ganciclovir, the drug used in those early studies.

In a small, randomized clinical trial published in 2003, the hearing of 25 infants born with symptomatic CMV infections and treated with ganciclovir did not deteriorate by 6 months; hearing deteriorated in 41% (7 of 17) of untreated infants. At or beyond age 1 year, hearing deteriorated in 21% (5 of 24) of ganciclovir-treated patients, compared with 68% (13 of 19) of controls (J. Pediatr. 2003;143:16-25).

The study did not lead to widespread use of ganciclovir for CMV hearing loss, however, because the results came only after the drug was given for 6 weeks through a central line, and because 63% of those treated developed grade 3 or 4 neutropenia.

Drug administration drawbacks, at least, will be avoided with the oral agent valganciclovir, she said.

An ongoing National Institutes of Health–funded study could shed light on the use of the drug; a 6-week course of valganciclovir is being tested against a 6-month course for CMV-related hearing loss and developmental delays.

About 1% of newborns are born with congenital CMV infections in Washington state, Dr. Sie noted. Nationwide, National Institutes of Health estimates range from 0.5% to 1.5%.

Between 22% and 65% will have hearing loss if they are born with CMV symptoms; the percentage is 6%-23%, if the infants are born asymptomatic (J. Clin. Virol. 2006;35:226-31).

CMV hearing loss can be either unilateral or bilateral, and vary in the severity and frequencies affected, Dr. Sie said. It is unclear how the virus damages hearing, but CMV has been detected in the perilymphatic spaces of the inner ear and the spiral ganglion, the location of the nerve endings in the inner ear.

The reason shell vial urine cultures can be done at or before 6 weeks of age is that an infected newborn will likely be shedding virus. Later, a neonatal blood spot PCR must be done to rule out postnatal infection, which is not thought to carry the same risk of hearing loss.

Although infants with hearing loss are not yet typically screened and treated for CMV, when they are, treatment is usually initiated only when the infection is caught by 6 months of age, Dr. Sie said. That misses later-onset CMV hearing loss.

Dr. Sie said he expects that in coming years, treatment will be initiated even if the diagnosis comes later. “We do know that [CMV-related] damage can continue for the first few years of life. So it's reasonable to think the window for treatment might extend beyond 6 months,” she said.

Disclosures: Dr. Sie reported that she had no conflicts of interest to disclose.

SEATTLE — If an infant fails a hearing test, think cytomegalovirus infection, advised Dr. Kathleen Sie.

Congenital cytomegalovirus (CMV) infection is now known to be the leading nongenetic cause of deafness in children, said Dr. Sie, clinical director of Seattle Children's Hospital's childhood communication center.

In infants with nongenetic hearing loss—at least 25% of cases—she recommended doing cytomegalovirus (CMV) screening by shell vial urine culture if the infant is within the first 6 weeks of life. Past that, the diagnosis must be made by polymerase chain reaction (PCR) testing of the neonatal blood spot.

If an infant is positive for CMV, treatment with valganciclovir, an oral antiviral agent, might halt or reverse hearing loss, Dr. Sie said at a conference sponsored by the North Pacific Pediatric Society.

Although not the standard of practice now, she said screening and treatment for pediatric CMV-related hearing loss will become increasingly common over the next 10 years. CMV will become the treatable cause of hearing loss in children because of promising results from small, early studies and because of the availability of valganciclovir, the active metabolite of ganciclovir, the drug used in those early studies.

In a small, randomized clinical trial published in 2003, the hearing of 25 infants born with symptomatic CMV infections and treated with ganciclovir did not deteriorate by 6 months; hearing deteriorated in 41% (7 of 17) of untreated infants. At or beyond age 1 year, hearing deteriorated in 21% (5 of 24) of ganciclovir-treated patients, compared with 68% (13 of 19) of controls (J. Pediatr. 2003;143:16-25).

The study did not lead to widespread use of ganciclovir for CMV hearing loss, however, because the results came only after the drug was given for 6 weeks through a central line, and because 63% of those treated developed grade 3 or 4 neutropenia.

Drug administration drawbacks, at least, will be avoided with the oral agent valganciclovir, she said.

An ongoing National Institutes of Health–funded study could shed light on the use of the drug; a 6-week course of valganciclovir is being tested against a 6-month course for CMV-related hearing loss and developmental delays.

About 1% of newborns are born with congenital CMV infections in Washington state, Dr. Sie noted. Nationwide, National Institutes of Health estimates range from 0.5% to 1.5%.

Between 22% and 65% will have hearing loss if they are born with CMV symptoms; the percentage is 6%-23%, if the infants are born asymptomatic (J. Clin. Virol. 2006;35:226-31).

CMV hearing loss can be either unilateral or bilateral, and vary in the severity and frequencies affected, Dr. Sie said. It is unclear how the virus damages hearing, but CMV has been detected in the perilymphatic spaces of the inner ear and the spiral ganglion, the location of the nerve endings in the inner ear.

The reason shell vial urine cultures can be done at or before 6 weeks of age is that an infected newborn will likely be shedding virus. Later, a neonatal blood spot PCR must be done to rule out postnatal infection, which is not thought to carry the same risk of hearing loss.

Although infants with hearing loss are not yet typically screened and treated for CMV, when they are, treatment is usually initiated only when the infection is caught by 6 months of age, Dr. Sie said. That misses later-onset CMV hearing loss.

Dr. Sie said he expects that in coming years, treatment will be initiated even if the diagnosis comes later. “We do know that [CMV-related] damage can continue for the first few years of life. So it's reasonable to think the window for treatment might extend beyond 6 months,” she said.

Disclosures: Dr. Sie reported that she had no conflicts of interest to disclose.

SEATTLE — If an infant fails a hearing test, think cytomegalovirus infection, advised Dr. Kathleen Sie.

Congenital cytomegalovirus (CMV) infection is now known to be the leading nongenetic cause of deafness in children, said Dr. Sie, clinical director of the Seattle Children's Hospital's childhood communication center.

In infants with nongenetic hearing loss—at least 25% of cases—she recommended doing cytomegalovirus (CMV) screening by shell vial urine culture if the infant is within the first 6 weeks of life.

Past that, the diagnosis must be made by polymerase chain reaction (PCR) testing of the neonatal blood spot.

If the infant is positive for CMV, treatment with valganciclovir, an oral antiviral agent, might halt or even reverse hearing loss, Dr. Sie said at a conference sponsored by the North Pacific Pediatric Society.

Although not the standard of practice now, she said screening and treatment for pediatric CMV-related hearing loss will become increasingly common over the next 10 years. CMV will become the treatable cause of hearing loss in children because of promising results from small, early studies and because of the availability of valganciclovir, the active metabolite of ganciclovir, the drug used in those early studies.

In a small, randomized clinical trial published in 2003, the hearing of 25 infants born with symptomatic CMV infections and treated with ganciclovir did not deteriorate by 6 months; hearing deteriorated in 41% (7 of 17) of untreated infants.

At or beyond age 1 year, hearing deteriorated in 21% (5 of 24) of ganciclovir-treated patients, compared with 68% (13 of 19) of controls (J. Pediatr. 2003;143:16–25).

The study did not lead to widespread use of ganciclovir for CMV hearing loss, however, because the results came only after the drug was given for 6 weeks through a central line, and because 63% of those treated developed grade 3 or 4 neutropenia.

Drug administration drawbacks, at least, will be avoided with the oral agent valganciclovir, she said.

An ongoing National Institutes of Health–funded study could shed light on the use of the drug; a 6-week course of valganciclovir is being tested against a 6-month course for CMV-related hearing loss and developmental delays.

About 1% of newborns are born with congenital CMV infections in Washington state, Dr. Sie noted. Nationwide, National Institutes of Health estimates range from 0.5% to 1.5%.

Between 22% and 65% will have hearing loss if they are born with CMV symptoms; the percentage is 6%–23%, if the infants are born asymptomatic (J. Clin. Virol. 2006;35:226–31).

CMV hearing loss can be either unilateral or bilateral, and vary in the severity and frequencies affected, Dr. Sie said. It is unclear how the virus damages hearing, but CMV has been detected in the perilymphatic spaces of the inner ear and the spiral ganglion, the location of the nerve endings in the inner ear.

The reason shell vial urine cultures can be done at or before 6 weeks of age is that an infected newborn will likely be shedding virus. Later, a neonatal blood spot PCR must be done to rule out postnatal infection, which is not thought to carry the same risk of hearing loss.

Although infants with hearing loss are not yet typically screened and treated for CMV, when they are, treatment is usually initiated only when the infection is caught by 6 months of age, Dr. Sie said. That misses later-onset CMV hearing loss.

Dr. Sie said she expects that in coming years, treatment will be initiated even if the diagnosis comes later.

“We do know that [CMV-related] damage can continue for the first few years of life.

“So it's reasonable to think the window for treatment might extend beyond 6 months,” she said.

Disclosures: None was reported.

SEATTLE — If an infant fails a hearing test, think cytomegalovirus infection, advised Dr. Kathleen Sie.

Congenital cytomegalovirus (CMV) infection is now known to be the leading nongenetic cause of deafness in children, said Dr. Sie, clinical director of the Seattle Children's Hospital's childhood communication center.

In infants with nongenetic hearing loss—at least 25% of cases—she recommended doing cytomegalovirus (CMV) screening by shell vial urine culture if the infant is within the first 6 weeks of life.

Past that, the diagnosis must be made by polymerase chain reaction (PCR) testing of the neonatal blood spot.

If the infant is positive for CMV, treatment with valganciclovir, an oral antiviral agent, might halt or even reverse hearing loss, Dr. Sie said at a conference sponsored by the North Pacific Pediatric Society.

Although not the standard of practice now, she said screening and treatment for pediatric CMV-related hearing loss will become increasingly common over the next 10 years. CMV will become the treatable cause of hearing loss in children because of promising results from small, early studies and because of the availability of valganciclovir, the active metabolite of ganciclovir, the drug used in those early studies.

In a small, randomized clinical trial published in 2003, the hearing of 25 infants born with symptomatic CMV infections and treated with ganciclovir did not deteriorate by 6 months; hearing deteriorated in 41% (7 of 17) of untreated infants.

At or beyond age 1 year, hearing deteriorated in 21% (5 of 24) of ganciclovir-treated patients, compared with 68% (13 of 19) of controls (J. Pediatr. 2003;143:16–25).

The study did not lead to widespread use of ganciclovir for CMV hearing loss, however, because the results came only after the drug was given for 6 weeks through a central line, and because 63% of those treated developed grade 3 or 4 neutropenia.

Drug administration drawbacks, at least, will be avoided with the oral agent valganciclovir, she said.

An ongoing National Institutes of Health–funded study could shed light on the use of the drug; a 6-week course of valganciclovir is being tested against a 6-month course for CMV-related hearing loss and developmental delays.

About 1% of newborns are born with congenital CMV infections in Washington state, Dr. Sie noted. Nationwide, National Institutes of Health estimates range from 0.5% to 1.5%.

Between 22% and 65% will have hearing loss if they are born with CMV symptoms; the percentage is 6%–23%, if the infants are born asymptomatic (J. Clin. Virol. 2006;35:226–31).

CMV hearing loss can be either unilateral or bilateral, and vary in the severity and frequencies affected, Dr. Sie said. It is unclear how the virus damages hearing, but CMV has been detected in the perilymphatic spaces of the inner ear and the spiral ganglion, the location of the nerve endings in the inner ear.

The reason shell vial urine cultures can be done at or before 6 weeks of age is that an infected newborn will likely be shedding virus. Later, a neonatal blood spot PCR must be done to rule out postnatal infection, which is not thought to carry the same risk of hearing loss.

Although infants with hearing loss are not yet typically screened and treated for CMV, when they are, treatment is usually initiated only when the infection is caught by 6 months of age, Dr. Sie said. That misses later-onset CMV hearing loss.

Dr. Sie said she expects that in coming years, treatment will be initiated even if the diagnosis comes later.

“We do know that [CMV-related] damage can continue for the first few years of life.

“So it's reasonable to think the window for treatment might extend beyond 6 months,” she said.

Disclosures: None was reported.

SEATTLE — If an infant fails a hearing test, think cytomegalovirus infection, advised Dr. Kathleen Sie.

Congenital cytomegalovirus (CMV) infection is now known to be the leading nongenetic cause of deafness in children, said Dr. Sie, clinical director of the Seattle Children's Hospital's childhood communication center.

In infants with nongenetic hearing loss—at least 25% of cases—she recommended doing cytomegalovirus (CMV) screening by shell vial urine culture if the infant is within the first 6 weeks of life.

Past that, the diagnosis must be made by polymerase chain reaction (PCR) testing of the neonatal blood spot.

If the infant is positive for CMV, treatment with valganciclovir, an oral antiviral agent, might halt or even reverse hearing loss, Dr. Sie said at a conference sponsored by the North Pacific Pediatric Society.

Although not the standard of practice now, she said screening and treatment for pediatric CMV-related hearing loss will become increasingly common over the next 10 years. CMV will become the treatable cause of hearing loss in children because of promising results from small, early studies and because of the availability of valganciclovir, the active metabolite of ganciclovir, the drug used in those early studies.

In a small, randomized clinical trial published in 2003, the hearing of 25 infants born with symptomatic CMV infections and treated with ganciclovir did not deteriorate by 6 months; hearing deteriorated in 41% (7 of 17) of untreated infants.

At or beyond age 1 year, hearing deteriorated in 21% (5 of 24) of ganciclovir-treated patients, compared with 68% (13 of 19) of controls (J. Pediatr. 2003;143:16–25).

The study did not lead to widespread use of ganciclovir for CMV hearing loss, however, because the results came only after the drug was given for 6 weeks through a central line, and because 63% of those treated developed grade 3 or 4 neutropenia.

Drug administration drawbacks, at least, will be avoided with the oral agent valganciclovir, she said.

An ongoing National Institutes of Health–funded study could shed light on the use of the drug; a 6-week course of valganciclovir is being tested against a 6-month course for CMV-related hearing loss and developmental delays.

About 1% of newborns are born with congenital CMV infections in Washington state, Dr. Sie noted. Nationwide, National Institutes of Health estimates range from 0.5% to 1.5%.

Between 22% and 65% will have hearing loss if they are born with CMV symptoms; the percentage is 6%–23%, if the infants are born asymptomatic (J. Clin. Virol. 2006;35:226–31).

CMV hearing loss can be either unilateral or bilateral, and vary in the severity and frequencies affected, Dr. Sie said. It is unclear how the virus damages hearing, but CMV has been detected in the perilymphatic spaces of the inner ear and the spiral ganglion, the location of the nerve endings in the inner ear.

The reason shell vial urine cultures can be done at or before 6 weeks of age is that an infected newborn will likely be shedding virus. Later, a neonatal blood spot PCR must be done to rule out postnatal infection, which is not thought to carry the same risk of hearing loss.

Although infants with hearing loss are not yet typically screened and treated for CMV, when they are, treatment is usually initiated only when the infection is caught by 6 months of age, Dr. Sie said. That misses later-onset CMV hearing loss.

Dr. Sie said she expects that in coming years, treatment will be initiated even if the diagnosis comes later.

“We do know that [CMV-related] damage can continue for the first few years of life.

“So it's reasonable to think the window for treatment might extend beyond 6 months,” she said.

Disclosures: None was reported.

SEATTLE — Take-home, ambulatory blood pressure monitors ensure more accurate blood pressure assessments and rule out white-coat hypertension, nephrologists at Seattle Children's Hospital's hypertension clinic have found.

The clinic ruled out white-coat hypertension in about 30%–40% of the roughly 200 children sent home with the monitors in 2009, according to Dr. Jodi Smith of the clinic

The results confirm studies that show ambulatory monitors rule out white-coat hypertension in up to 50% of patients, an improvement over in-office readings, Dr. Smith said at a conference sponsored by the North Pacific Pediatric Society.

Although more expensive than an office blood pressure reading, “if used as first line, before doing a bunch of other diagnostic tests, it can decrease costs” overall, said Dr. Smith, who, along with her nephrologist colleagues, sees patients in the hospital's hypertension clinic due to the correlation of pediatric hypertension and renal problems.

The clinic uses ambulatory monitors made by SpaceLabs Medical, Inc., of Issaquah, Wash. They cost about $3,000 each.

Motivated by favorable studies, the hypertension clinic started using the monitors about a year ago, switching from office readings and automated blood pressure cuffs that caretakers used to take a few measurements a day at home.

The units consist of a blood pressure cuff and an iPod-sized monitor that is worn around the waist and easily concealed under a sweatshirt. The cuffs inflate every 20-30 minutes for 24 hours.

Older kids adapt well to the frequent squeezes, Dr. Smith said, but the approach wouldn't be appropriate for children under age 7 or so.

The read-outs go far beyond a listing of systolic and diastolic pressures, and are complicated to interpret, she said. “They look for patterns,” including blood pressure load, and the presence—or not—of a normal drop in blood pressure at night.

Children also keep an activity log, so a spike in blood pressure during a soccer game, for instance, isn't misinterpreted.

It's a first-line assessment at the clinic, especially to confirm hypertension in otherwise healthy children.

Schedulers get prior insurance authorization for an ambulatory monitor before the child comes in, so they can be sent home with one after the first visit.

Her clinic matches readings to a chart in the National Heart, Lung, and Blood Institute's Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Pediatrics 2004;114:555-76).

“We get calls all the time [from physicians wondering] what's normal and what's not,” she said. “Normals change through childhood. It is hard to define what level is dangerous.”

The chart helps. At her clinic, blood pressures at or above the 90th percentile trigger intervention.

Kids who fall between the 90th and 94th percentile are considered pre-hypertensive, the point at which lifestyle changes are initiated along with medication if there are comorbidities.

At or above the 95th percentile, children are deemed hypertensive. Treatment and drug selection depend on cause, symptoms, the presence of end-organ damage or diabetes, and other considerations.

With increasing rates of obesity, primary hypertension is on the rise in the pediatric population, but hypertensive kids are still more likely than adults to have definable causes for the condition.

Renal problems are most likely, followed by renovascular, endocrine, and genetic problems, Dr. Smith said.

Dr. Smith had no conflicts of interest to report.

SEATTLE — Take-home, ambulatory blood pressure monitors ensure more accurate blood pressure assessments and rule out white-coat hypertension, nephrologists at Seattle Children's Hospital's hypertension clinic have found.

The clinic ruled out white-coat hypertension in about 30%–40% of the roughly 200 children sent home with the monitors in 2009, according to Dr. Jodi Smith of the clinic

The results confirm studies that show ambulatory monitors rule out white-coat hypertension in up to 50% of patients, an improvement over in-office readings, Dr. Smith said at a conference sponsored by the North Pacific Pediatric Society.

Although more expensive than an office blood pressure reading, “if used as first line, before doing a bunch of other diagnostic tests, it can decrease costs” overall, said Dr. Smith, who, along with her nephrologist colleagues, sees patients in the hospital's hypertension clinic due to the correlation of pediatric hypertension and renal problems.

The clinic uses ambulatory monitors made by SpaceLabs Medical, Inc., of Issaquah, Wash. They cost about $3,000 each.

Motivated by favorable studies, the hypertension clinic started using the monitors about a year ago, switching from office readings and automated blood pressure cuffs that caretakers used to take a few measurements a day at home.

The units consist of a blood pressure cuff and an iPod-sized monitor that is worn around the waist and easily concealed under a sweatshirt. The cuffs inflate every 20-30 minutes for 24 hours.

Older kids adapt well to the frequent squeezes, Dr. Smith said, but the approach wouldn't be appropriate for children under age 7 or so.

The read-outs go far beyond a listing of systolic and diastolic pressures, and are complicated to interpret, she said. “They look for patterns,” including blood pressure load, and the presence—or not—of a normal drop in blood pressure at night.

Children also keep an activity log, so a spike in blood pressure during a soccer game, for instance, isn't misinterpreted.

It's a first-line assessment at the clinic, especially to confirm hypertension in otherwise healthy children.

Schedulers get prior insurance authorization for an ambulatory monitor before the child comes in, so they can be sent home with one after the first visit.

Her clinic matches readings to a chart in the National Heart, Lung, and Blood Institute's Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Pediatrics 2004;114:555-76).

“We get calls all the time [from physicians wondering] what's normal and what's not,” she said. “Normals change through childhood. It is hard to define what level is dangerous.”

The chart helps. At her clinic, blood pressures at or above the 90th percentile trigger intervention.

Kids who fall between the 90th and 94th percentile are considered pre-hypertensive, the point at which lifestyle changes are initiated along with medication if there are comorbidities.

At or above the 95th percentile, children are deemed hypertensive. Treatment and drug selection depend on cause, symptoms, the presence of end-organ damage or diabetes, and other considerations.

With increasing rates of obesity, primary hypertension is on the rise in the pediatric population, but hypertensive kids are still more likely than adults to have definable causes for the condition.

Renal problems are most likely, followed by renovascular, endocrine, and genetic problems, Dr. Smith said.

Dr. Smith had no conflicts of interest to report.

SEATTLE — Take-home, ambulatory blood pressure monitors ensure more accurate blood pressure assessments and rule out white-coat hypertension, nephrologists at Seattle Children's Hospital's hypertension clinic have found.

The clinic ruled out white-coat hypertension in about 30%–40% of the roughly 200 children sent home with the monitors in 2009, according to Dr. Jodi Smith of the clinic

The results confirm studies that show ambulatory monitors rule out white-coat hypertension in up to 50% of patients, an improvement over in-office readings, Dr. Smith said at a conference sponsored by the North Pacific Pediatric Society.

Although more expensive than an office blood pressure reading, “if used as first line, before doing a bunch of other diagnostic tests, it can decrease costs” overall, said Dr. Smith, who, along with her nephrologist colleagues, sees patients in the hospital's hypertension clinic due to the correlation of pediatric hypertension and renal problems.

The clinic uses ambulatory monitors made by SpaceLabs Medical, Inc., of Issaquah, Wash. They cost about $3,000 each.

Motivated by favorable studies, the hypertension clinic started using the monitors about a year ago, switching from office readings and automated blood pressure cuffs that caretakers used to take a few measurements a day at home.

The units consist of a blood pressure cuff and an iPod-sized monitor that is worn around the waist and easily concealed under a sweatshirt. The cuffs inflate every 20-30 minutes for 24 hours.

Older kids adapt well to the frequent squeezes, Dr. Smith said, but the approach wouldn't be appropriate for children under age 7 or so.

The read-outs go far beyond a listing of systolic and diastolic pressures, and are complicated to interpret, she said. “They look for patterns,” including blood pressure load, and the presence—or not—of a normal drop in blood pressure at night.

Children also keep an activity log, so a spike in blood pressure during a soccer game, for instance, isn't misinterpreted.

It's a first-line assessment at the clinic, especially to confirm hypertension in otherwise healthy children.

Schedulers get prior insurance authorization for an ambulatory monitor before the child comes in, so they can be sent home with one after the first visit.

Her clinic matches readings to a chart in the National Heart, Lung, and Blood Institute's Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Pediatrics 2004;114:555-76).

“We get calls all the time [from physicians wondering] what's normal and what's not,” she said. “Normals change through childhood. It is hard to define what level is dangerous.”

The chart helps. At her clinic, blood pressures at or above the 90th percentile trigger intervention.

Kids who fall between the 90th and 94th percentile are considered pre-hypertensive, the point at which lifestyle changes are initiated along with medication if there are comorbidities.

At or above the 95th percentile, children are deemed hypertensive. Treatment and drug selection depend on cause, symptoms, the presence of end-organ damage or diabetes, and other considerations.

With increasing rates of obesity, primary hypertension is on the rise in the pediatric population, but hypertensive kids are still more likely than adults to have definable causes for the condition.

Renal problems are most likely, followed by renovascular, endocrine, and genetic problems, Dr. Smith said.

Dr. Smith had no conflicts of interest to report.