Jane Salodof MacNeil

ALBUQUERQUE — Community-acquired methicillin-resistant Staphylococcus aureus is causing a growing number of sudden, severe musculoskeletal infections in otherwise healthy children, according to reports at the annual meeting of the Pediatric Orthopaedic Society of North America.

In separate interviews, Dr. John P. Lubicky, professor of orthopedic surgery at Indiana University, and Dr. Shawn R. Gilbert of the University of Alabama at Birmingham, suggested that unfamiliarity with musculoskeletal presentation of community-acquired MRSA infections may be causing dangerous delays in diagnosis.

“The kids are sick as hell. Some nearly die,” Dr. Lubicky said, urging clinicians to raise their index of suspicion.

Searching for MRSA-positive musculoskeletal infections treated from January 2003 to February 2008, Dr. Lubicky found 12 community-acquired cases in children who did not have an underlying disease. The average age was 7.2 years (range 0.2–17.7 years). Nine were boys.

“A lot of the kids are blatantly healthy,” Dr. Lubicky said, emphasizing that the children in the retrospective study had been active before taking sick.

The average hospital stay was 20.5 days (range 4–42 days). Eleven children required surgical interventions. Complications included pyomyositis in 7 children, septic arthritis in 6, and osteomyelitis in 10 (among them 3 cases that were multifocal and 2 fractures). Four children had septic emboli. One had pneumonia.

Dr. Lubicky recommended magnetic resonance imaging of the whole body to check for multiple remote sites. Abscesses should be drained early and repeatedly.

Dr. Lubicky said to start empiric antibiotic treatment against both methicillin-susceptible and methicillin-resistant bacterial strains. A 6-week course, starting with parenteral administration and followed by oral antibiotics against susceptible isolates, is usually adequate, they said. Eight children in the retrospective study were treated with vancomycin and clindamycin.

In Alabama, Dr. Gilbert and colleagues found 156 cases of culture-proven S. aureus infections when they searched community-acquired septic arthritis or osteomyelitis cases from 2001 to 2007. Of these, 66 cases (42%) were methicillin resistant, including 8 cases of multifocal musculoskeletal infection. In comparison, only 1 child among 90 with methicillin-sensitive infection was affected at more than one site—bringing the total number of multifocal musculoskeletal S. aureus infections to 9.

The number of multifocal infections doubled from three during 2001–2004 to six during 2005–2007. The number of sites also increased from 2–3 during the early period to 2–7 (average 3.8) during the later years.

Serious complications became more common over time. One child had bacteremia and none had septic emboli in the early multifocal group. Among the multifocal cases after 2004, four children presented with bacteremia and all six children had septic emboli. “Some joints that were affected weren't symptomatic, either because [the children] weren't having pain or they were so sick they couldn't tell you what was hurting,” Dr. Gilbert said. He routinely samples all high-risk joints as well as any joints with obvious swelling.

Left: A chest with right parietal osteomyelitis, soft tissue swelling, and multiple lung abscesses. Right: An image is shown of a femur shows left hip effusion, left femoral osteo-myelitis, left thigh pyomyositis, and right proximal tibia osteomyelitis. Images courtesy Dr. John P. Lubicky

ALBUQUERQUE — Community-acquired methicillin-resistant Staphylococcus aureus is causing a growing number of sudden, severe musculoskeletal infections in otherwise healthy children, according to reports at the annual meeting of the Pediatric Orthopaedic Society of North America.

In separate interviews, Dr. John P. Lubicky, professor of orthopedic surgery at Indiana University, and Dr. Shawn R. Gilbert of the University of Alabama at Birmingham, suggested that unfamiliarity with musculoskeletal presentation of community-acquired MRSA infections may be causing dangerous delays in diagnosis.

“The kids are sick as hell. Some nearly die,” Dr. Lubicky said, urging clinicians to raise their index of suspicion.

Searching for MRSA-positive musculoskeletal infections treated from January 2003 to February 2008, Dr. Lubicky found 12 community-acquired cases in children who did not have an underlying disease. The average age was 7.2 years (range 0.2–17.7 years). Nine were boys.

“A lot of the kids are blatantly healthy,” Dr. Lubicky said, emphasizing that the children in the retrospective study had been active before taking sick.

The average hospital stay was 20.5 days (range 4–42 days). Eleven children required surgical interventions. Complications included pyomyositis in 7 children, septic arthritis in 6, and osteomyelitis in 10 (among them 3 cases that were multifocal and 2 fractures). Four children had septic emboli. One had pneumonia.

Dr. Lubicky recommended magnetic resonance imaging of the whole body to check for multiple remote sites. Abscesses should be drained early and repeatedly.

Dr. Lubicky said to start empiric antibiotic treatment against both methicillin-susceptible and methicillin-resistant bacterial strains. A 6-week course, starting with parenteral administration and followed by oral antibiotics against susceptible isolates, is usually adequate, they said. Eight children in the retrospective study were treated with vancomycin and clindamycin.

In Alabama, Dr. Gilbert and colleagues found 156 cases of culture-proven S. aureus infections when they searched community-acquired septic arthritis or osteomyelitis cases from 2001 to 2007. Of these, 66 cases (42%) were methicillin resistant, including 8 cases of multifocal musculoskeletal infection. In comparison, only 1 child among 90 with methicillin-sensitive infection was affected at more than one site—bringing the total number of multifocal musculoskeletal S. aureus infections to 9.

The number of multifocal infections doubled from three during 2001–2004 to six during 2005–2007. The number of sites also increased from 2–3 during the early period to 2–7 (average 3.8) during the later years.

Serious complications became more common over time. One child had bacteremia and none had septic emboli in the early multifocal group. Among the multifocal cases after 2004, four children presented with bacteremia and all six children had septic emboli. “Some joints that were affected weren't symptomatic, either because [the children] weren't having pain or they were so sick they couldn't tell you what was hurting,” Dr. Gilbert said. He routinely samples all high-risk joints as well as any joints with obvious swelling.

Left: A chest with right parietal osteomyelitis, soft tissue swelling, and multiple lung abscesses. Right: An image is shown of a femur shows left hip effusion, left femoral osteo-myelitis, left thigh pyomyositis, and right proximal tibia osteomyelitis. Images courtesy Dr. John P. Lubicky

ALBUQUERQUE — Community-acquired methicillin-resistant Staphylococcus aureus is causing a growing number of sudden, severe musculoskeletal infections in otherwise healthy children, according to reports at the annual meeting of the Pediatric Orthopaedic Society of North America.

In separate interviews, Dr. John P. Lubicky, professor of orthopedic surgery at Indiana University, and Dr. Shawn R. Gilbert of the University of Alabama at Birmingham, suggested that unfamiliarity with musculoskeletal presentation of community-acquired MRSA infections may be causing dangerous delays in diagnosis.

“The kids are sick as hell. Some nearly die,” Dr. Lubicky said, urging clinicians to raise their index of suspicion.

Searching for MRSA-positive musculoskeletal infections treated from January 2003 to February 2008, Dr. Lubicky found 12 community-acquired cases in children who did not have an underlying disease. The average age was 7.2 years (range 0.2–17.7 years). Nine were boys.

“A lot of the kids are blatantly healthy,” Dr. Lubicky said, emphasizing that the children in the retrospective study had been active before taking sick.

The average hospital stay was 20.5 days (range 4–42 days). Eleven children required surgical interventions. Complications included pyomyositis in 7 children, septic arthritis in 6, and osteomyelitis in 10 (among them 3 cases that were multifocal and 2 fractures). Four children had septic emboli. One had pneumonia.

Dr. Lubicky recommended magnetic resonance imaging of the whole body to check for multiple remote sites. Abscesses should be drained early and repeatedly.

Dr. Lubicky said to start empiric antibiotic treatment against both methicillin-susceptible and methicillin-resistant bacterial strains. A 6-week course, starting with parenteral administration and followed by oral antibiotics against susceptible isolates, is usually adequate, they said. Eight children in the retrospective study were treated with vancomycin and clindamycin.

In Alabama, Dr. Gilbert and colleagues found 156 cases of culture-proven S. aureus infections when they searched community-acquired septic arthritis or osteomyelitis cases from 2001 to 2007. Of these, 66 cases (42%) were methicillin resistant, including 8 cases of multifocal musculoskeletal infection. In comparison, only 1 child among 90 with methicillin-sensitive infection was affected at more than one site—bringing the total number of multifocal musculoskeletal S. aureus infections to 9.

The number of multifocal infections doubled from three during 2001–2004 to six during 2005–2007. The number of sites also increased from 2–3 during the early period to 2–7 (average 3.8) during the later years.

Serious complications became more common over time. One child had bacteremia and none had septic emboli in the early multifocal group. Among the multifocal cases after 2004, four children presented with bacteremia and all six children had septic emboli. “Some joints that were affected weren't symptomatic, either because [the children] weren't having pain or they were so sick they couldn't tell you what was hurting,” Dr. Gilbert said. He routinely samples all high-risk joints as well as any joints with obvious swelling.

Left: A chest with right parietal osteomyelitis, soft tissue swelling, and multiple lung abscesses. Right: An image is shown of a femur shows left hip effusion, left femoral osteo-myelitis, left thigh pyomyositis, and right proximal tibia osteomyelitis. Images courtesy Dr. John P. Lubicky

ALBUQUERQUE — A prospective pilot study of 41 children with complaints of nonspecific musculoskeletal pain found their average levels of vitamin D were low even though the youngsters lived in the sunny southwest of the United States.

The mean level of serum 25-hydroxyvitamin D was lower in a group of 35 children with vague pain complaints than in 6 children found to have diagnosable conditions that explained their pain: 28 ng/mL vs. 38 ng/mL. While this difference was statistically significant, average vitamin D levels in both groups of children (aged 2–17 years) met the study's definition of hypovitaminosis D.

Moreover, when eight children were given vitamin D supplements, five had “marked subjective improvement or complete relief” from pain. Those making a recovery included one of two children with documented hip effusion as well as children with back pains and leg pains that had lasted, in some cases, for years.

“I am certainly not saying growing pains are caused by vitamin D deficiency, but it is something we are exploring,” Dr. Elizabeth A. Szalay said in an interview after presenting the data at the annual meeting of the Pediatric Orthopaedic Society of North America.

What was, perhaps, most remarkable, was that the children lived in New Mexico at latitude 31 degrees north—an area not typically used in vitamin D studies because it has abundant sunshine year round. The National Health and Nutrition Examination Survey III suggests that 3% of healthy adolescents at a higher latitude have vitamin D levels below 25 ng/mL during summer, she said. In the New Mexico study, 30% of the youngsters in pain had vitamin D levels below 25 ng/mL.

Dr. Szalay, an orthopedic surgeon at the University of New Mexico and Carrie Tingley Hospital, both in Albuquerque, and her coinvestigator Elyce B. Tryon used a local laboratory's classification of vitamin D levels in their analysis. Ranges were presented as 0–5 ng/mL for deficiency, 5–20 ng/mL for insufficiency, 20–40 ng/mL for hypovitaminosis D, 40–100 ng/mL for sufficiency, and more than 100 ng/mL for toxicity.

The highest level recorded was 47 ng/mL. It was seen in both subgroups: the children with vague complaints and those with objective explanations of their pain (Legg-Calvé-Perthes disease, arthrogryposis, and chondrolysis). The lowest level in the majority with vague complaints was less than half that of the children with diagnoses: 12 ng/mL vs. 25 ng/mL.

Dr. Szalay speculated that the low levels of vitamin D could be attributed to a convergence of factors. Sunlight is a prime source of vitamin D and 15 minutes of exposure a day is sufficient, she said, but many children do not play outside. They don't walk to school and may spend as much as 44 hours a week on electronic media such as video games.

Diet by itself is unlikely to provide enough vitamin D, she continued. Milk is fortified with vitamin D, but consumption is down, compared with years past. “In 1970, children drank twice as much milk as soda,” she said. “In 2000, children drank twice as much soda as milk.”

Children's multivitamins do not make up for vitamin D deficiency, according to Dr. Szalay. Some only contain 64 U a day, she said, recommending that children at risk take both a multivitamin and a chewy calcium-plus-D supplement plus two glasses of milk a day. For children without pain, she set the desired daily intake at 800–1,000 U of vitamin D, but added that she recommends 1,000–2,000 U for children with pain.

'I am certainly not saying growing pains are caused by vitamin D deficiency, but it is something we are exploring.' DR. SZALAY

ALBUQUERQUE — A prospective pilot study of 41 children with complaints of nonspecific musculoskeletal pain found their average levels of vitamin D were low even though the youngsters lived in the sunny southwest of the United States.

The mean level of serum 25-hydroxyvitamin D was lower in a group of 35 children with vague pain complaints than in 6 children found to have diagnosable conditions that explained their pain: 28 ng/mL vs. 38 ng/mL. While this difference was statistically significant, average vitamin D levels in both groups of children (aged 2–17 years) met the study's definition of hypovitaminosis D.

Moreover, when eight children were given vitamin D supplements, five had “marked subjective improvement or complete relief” from pain. Those making a recovery included one of two children with documented hip effusion as well as children with back pains and leg pains that had lasted, in some cases, for years.

“I am certainly not saying growing pains are caused by vitamin D deficiency, but it is something we are exploring,” Dr. Elizabeth A. Szalay said in an interview after presenting the data at the annual meeting of the Pediatric Orthopaedic Society of North America.

What was, perhaps, most remarkable, was that the children lived in New Mexico at latitude 31 degrees north—an area not typically used in vitamin D studies because it has abundant sunshine year round. The National Health and Nutrition Examination Survey III suggests that 3% of healthy adolescents at a higher latitude have vitamin D levels below 25 ng/mL during summer, she said. In the New Mexico study, 30% of the youngsters in pain had vitamin D levels below 25 ng/mL.

Dr. Szalay, an orthopedic surgeon at the University of New Mexico and Carrie Tingley Hospital, both in Albuquerque, and her coinvestigator Elyce B. Tryon used a local laboratory's classification of vitamin D levels in their analysis. Ranges were presented as 0–5 ng/mL for deficiency, 5–20 ng/mL for insufficiency, 20–40 ng/mL for hypovitaminosis D, 40–100 ng/mL for sufficiency, and more than 100 ng/mL for toxicity.

The highest level recorded was 47 ng/mL. It was seen in both subgroups: the children with vague complaints and those with objective explanations of their pain (Legg-Calvé-Perthes disease, arthrogryposis, and chondrolysis). The lowest level in the majority with vague complaints was less than half that of the children with diagnoses: 12 ng/mL vs. 25 ng/mL.

Dr. Szalay speculated that the low levels of vitamin D could be attributed to a convergence of factors. Sunlight is a prime source of vitamin D and 15 minutes of exposure a day is sufficient, she said, but many children do not play outside. They don't walk to school and may spend as much as 44 hours a week on electronic media such as video games.

Diet by itself is unlikely to provide enough vitamin D, she continued. Milk is fortified with vitamin D, but consumption is down, compared with years past. “In 1970, children drank twice as much milk as soda,” she said. “In 2000, children drank twice as much soda as milk.”

Children's multivitamins do not make up for vitamin D deficiency, according to Dr. Szalay. Some only contain 64 U a day, she said, recommending that children at risk take both a multivitamin and a chewy calcium-plus-D supplement plus two glasses of milk a day. For children without pain, she set the desired daily intake at 800–1,000 U of vitamin D, but added that she recommends 1,000–2,000 U for children with pain.

'I am certainly not saying growing pains are caused by vitamin D deficiency, but it is something we are exploring.' DR. SZALAY

ALBUQUERQUE — A prospective pilot study of 41 children with complaints of nonspecific musculoskeletal pain found their average levels of vitamin D were low even though the youngsters lived in the sunny southwest of the United States.

The mean level of serum 25-hydroxyvitamin D was lower in a group of 35 children with vague pain complaints than in 6 children found to have diagnosable conditions that explained their pain: 28 ng/mL vs. 38 ng/mL. While this difference was statistically significant, average vitamin D levels in both groups of children (aged 2–17 years) met the study's definition of hypovitaminosis D.

Moreover, when eight children were given vitamin D supplements, five had “marked subjective improvement or complete relief” from pain. Those making a recovery included one of two children with documented hip effusion as well as children with back pains and leg pains that had lasted, in some cases, for years.

“I am certainly not saying growing pains are caused by vitamin D deficiency, but it is something we are exploring,” Dr. Elizabeth A. Szalay said in an interview after presenting the data at the annual meeting of the Pediatric Orthopaedic Society of North America.

What was, perhaps, most remarkable, was that the children lived in New Mexico at latitude 31 degrees north—an area not typically used in vitamin D studies because it has abundant sunshine year round. The National Health and Nutrition Examination Survey III suggests that 3% of healthy adolescents at a higher latitude have vitamin D levels below 25 ng/mL during summer, she said. In the New Mexico study, 30% of the youngsters in pain had vitamin D levels below 25 ng/mL.

Dr. Szalay, an orthopedic surgeon at the University of New Mexico and Carrie Tingley Hospital, both in Albuquerque, and her coinvestigator Elyce B. Tryon used a local laboratory's classification of vitamin D levels in their analysis. Ranges were presented as 0–5 ng/mL for deficiency, 5–20 ng/mL for insufficiency, 20–40 ng/mL for hypovitaminosis D, 40–100 ng/mL for sufficiency, and more than 100 ng/mL for toxicity.

The highest level recorded was 47 ng/mL. It was seen in both subgroups: the children with vague complaints and those with objective explanations of their pain (Legg-Calvé-Perthes disease, arthrogryposis, and chondrolysis). The lowest level in the majority with vague complaints was less than half that of the children with diagnoses: 12 ng/mL vs. 25 ng/mL.

Dr. Szalay speculated that the low levels of vitamin D could be attributed to a convergence of factors. Sunlight is a prime source of vitamin D and 15 minutes of exposure a day is sufficient, she said, but many children do not play outside. They don't walk to school and may spend as much as 44 hours a week on electronic media such as video games.

Diet by itself is unlikely to provide enough vitamin D, she continued. Milk is fortified with vitamin D, but consumption is down, compared with years past. “In 1970, children drank twice as much milk as soda,” she said. “In 2000, children drank twice as much soda as milk.”

Children's multivitamins do not make up for vitamin D deficiency, according to Dr. Szalay. Some only contain 64 U a day, she said, recommending that children at risk take both a multivitamin and a chewy calcium-plus-D supplement plus two glasses of milk a day. For children without pain, she set the desired daily intake at 800–1,000 U of vitamin D, but added that she recommends 1,000–2,000 U for children with pain.

'I am certainly not saying growing pains are caused by vitamin D deficiency, but it is something we are exploring.' DR. SZALAY

ALBUQUERQUE — Community-acquired methicillin-resistant Staphylococcus aureus is causing a growing number of sudden, severe musculoskeletal infections in otherwise healthy children, according to two reports at the annual meeting of the Pediatric Orthopaedic Society of North America.

Investigators from Indiana University in Indianapolis and from Children's Hospital of Alabama in Birmingham warned in separate posters that sepsis and other comorbidities are common in these cases along with multiple, sometimes asymptomatic, sites of involvement.

In separate interviews, Dr. John P. Lubicky, of Indiana University, and Dr. Shawn R. Gilbert of the University of Alabama at Birmingham suggested that unfamiliarity with musculoskeletal presentation of community-acquired MRSA infections may be causing dangerous delays in diagnosis.

"The kids are sick as hell. Some nearly die," Dr. Lubicky said, urging clinicians to raise their index of suspicion. Unless a physician has seen one of these infections before, he said, community-acquired MRSA is not likely to come to mind when children present with fever and don't move around much.

"Several of the patients had signs of infection in a knee or ankle for a few days, and it took them a while to get appropriate treatment," Dr. Gilbert said, calling for more aggressive treatment when these infections present.

The Indiana Experience

Searching for MRSA-positive musculoskeletal infections treated from January 2003 to February 2008, Dr. Lubicky and his coauthors found 12 community-acquired cases in children who did not have an underlying disease. The average age was 7.2 years (range 0.2–17.7 years). Nine of the children were boys.

"A lot of the kids are blatantly healthy. There is no obvious source for them to get infected," Dr. Lubicky said, emphasizing that the children in the retrospective study had been active before taking sick. One boy, he recalled, recently had fallen off a skateboard.

Long hospital stays were the norm with an average of 20.5 days (range 4–42 days). Eleven children required surgical interventions. Complications included pyomyositis in 7 children, septic arthritis in 6 children, and osteomyelitis in 10 children (among them 3 cases that were multifocal and 2 that were fractures). Four children had septic emboli and one had pneumonia.

Dr. Lubicky and his colleagues recommended magnetic resonance imaging of the whole body, if possible, to check for multiple remote sites when community-acquired MRSA is suspected. Treatment often involves medical and surgical interventions, they said, warning that abscesses should be drained early and may need to be drained repeatedly.

The investigators said to start empiric antibiotic treatment against both methicillin-susceptible and methicillin-resistant bacterial strains. A 6-week course of treatment, starting with parenteral administration and followed by oral antibiotics against susceptible isolates, is usually adequate, they said. Eight children in the retrospective study were treated with vancomycin and clindamycin.

The Alabama Experience

Dr. Gilbert and his colleagues found 156 cases of culture-proven S. aureus infections when they searched community-acquired septic arthritis or osteomyelitis cases from 2001 to 2007. Of these, 66 cases (42%) were methicillin resistant, including 8 cases of multifocal musculoskeletal infection. In comparison, only 1 child among 90 with methicillin-sensitive infection was affected at more than one site—bringing the total number of multifocal musculoskeletal S. aureus infections to 9.

The number of multifocal infections doubled from three during 2001–2004 to six during 2005–2007. The number of sites also increased from 2–3 during the early period to 2–7 (average 3.8) during the later years.

Serious complications became more common over time as well. One child had bacteremia and none had septic emboli in the early multifocal group. Among the multifocal cases after 2004, four children presented with bacteremia and all six children had septic emboli. Dr. Gilbert said that he now routinely samples all high-risk joints, such as the hips, and any joints with obvious swelling.

Several 'had signs of infection in a knee or ankle for a few days, and it took them a while to get appropriate treatment.' DR. GILBERT

ALBUQUERQUE — Community-acquired methicillin-resistant Staphylococcus aureus is causing a growing number of sudden, severe musculoskeletal infections in otherwise healthy children, according to two reports at the annual meeting of the Pediatric Orthopaedic Society of North America.

Investigators from Indiana University in Indianapolis and from Children's Hospital of Alabama in Birmingham warned in separate posters that sepsis and other comorbidities are common in these cases along with multiple, sometimes asymptomatic, sites of involvement.

In separate interviews, Dr. John P. Lubicky, of Indiana University, and Dr. Shawn R. Gilbert of the University of Alabama at Birmingham suggested that unfamiliarity with musculoskeletal presentation of community-acquired MRSA infections may be causing dangerous delays in diagnosis.

"The kids are sick as hell. Some nearly die," Dr. Lubicky said, urging clinicians to raise their index of suspicion. Unless a physician has seen one of these infections before, he said, community-acquired MRSA is not likely to come to mind when children present with fever and don't move around much.

"Several of the patients had signs of infection in a knee or ankle for a few days, and it took them a while to get appropriate treatment," Dr. Gilbert said, calling for more aggressive treatment when these infections present.

The Indiana Experience

Searching for MRSA-positive musculoskeletal infections treated from January 2003 to February 2008, Dr. Lubicky and his coauthors found 12 community-acquired cases in children who did not have an underlying disease. The average age was 7.2 years (range 0.2–17.7 years). Nine of the children were boys.

"A lot of the kids are blatantly healthy. There is no obvious source for them to get infected," Dr. Lubicky said, emphasizing that the children in the retrospective study had been active before taking sick. One boy, he recalled, recently had fallen off a skateboard.

Long hospital stays were the norm with an average of 20.5 days (range 4–42 days). Eleven children required surgical interventions. Complications included pyomyositis in 7 children, septic arthritis in 6 children, and osteomyelitis in 10 children (among them 3 cases that were multifocal and 2 that were fractures). Four children had septic emboli and one had pneumonia.

Dr. Lubicky and his colleagues recommended magnetic resonance imaging of the whole body, if possible, to check for multiple remote sites when community-acquired MRSA is suspected. Treatment often involves medical and surgical interventions, they said, warning that abscesses should be drained early and may need to be drained repeatedly.

The investigators said to start empiric antibiotic treatment against both methicillin-susceptible and methicillin-resistant bacterial strains. A 6-week course of treatment, starting with parenteral administration and followed by oral antibiotics against susceptible isolates, is usually adequate, they said. Eight children in the retrospective study were treated with vancomycin and clindamycin.

The Alabama Experience

Dr. Gilbert and his colleagues found 156 cases of culture-proven S. aureus infections when they searched community-acquired septic arthritis or osteomyelitis cases from 2001 to 2007. Of these, 66 cases (42%) were methicillin resistant, including 8 cases of multifocal musculoskeletal infection. In comparison, only 1 child among 90 with methicillin-sensitive infection was affected at more than one site—bringing the total number of multifocal musculoskeletal S. aureus infections to 9.

The number of multifocal infections doubled from three during 2001–2004 to six during 2005–2007. The number of sites also increased from 2–3 during the early period to 2–7 (average 3.8) during the later years.

Serious complications became more common over time as well. One child had bacteremia and none had septic emboli in the early multifocal group. Among the multifocal cases after 2004, four children presented with bacteremia and all six children had septic emboli. Dr. Gilbert said that he now routinely samples all high-risk joints, such as the hips, and any joints with obvious swelling.

Several 'had signs of infection in a knee or ankle for a few days, and it took them a while to get appropriate treatment.' DR. GILBERT

ALBUQUERQUE — Community-acquired methicillin-resistant Staphylococcus aureus is causing a growing number of sudden, severe musculoskeletal infections in otherwise healthy children, according to two reports at the annual meeting of the Pediatric Orthopaedic Society of North America.

Investigators from Indiana University in Indianapolis and from Children's Hospital of Alabama in Birmingham warned in separate posters that sepsis and other comorbidities are common in these cases along with multiple, sometimes asymptomatic, sites of involvement.

In separate interviews, Dr. John P. Lubicky, of Indiana University, and Dr. Shawn R. Gilbert of the University of Alabama at Birmingham suggested that unfamiliarity with musculoskeletal presentation of community-acquired MRSA infections may be causing dangerous delays in diagnosis.

"The kids are sick as hell. Some nearly die," Dr. Lubicky said, urging clinicians to raise their index of suspicion. Unless a physician has seen one of these infections before, he said, community-acquired MRSA is not likely to come to mind when children present with fever and don't move around much.

"Several of the patients had signs of infection in a knee or ankle for a few days, and it took them a while to get appropriate treatment," Dr. Gilbert said, calling for more aggressive treatment when these infections present.

The Indiana Experience

Searching for MRSA-positive musculoskeletal infections treated from January 2003 to February 2008, Dr. Lubicky and his coauthors found 12 community-acquired cases in children who did not have an underlying disease. The average age was 7.2 years (range 0.2–17.7 years). Nine of the children were boys.

"A lot of the kids are blatantly healthy. There is no obvious source for them to get infected," Dr. Lubicky said, emphasizing that the children in the retrospective study had been active before taking sick. One boy, he recalled, recently had fallen off a skateboard.

Long hospital stays were the norm with an average of 20.5 days (range 4–42 days). Eleven children required surgical interventions. Complications included pyomyositis in 7 children, septic arthritis in 6 children, and osteomyelitis in 10 children (among them 3 cases that were multifocal and 2 that were fractures). Four children had septic emboli and one had pneumonia.

Dr. Lubicky and his colleagues recommended magnetic resonance imaging of the whole body, if possible, to check for multiple remote sites when community-acquired MRSA is suspected. Treatment often involves medical and surgical interventions, they said, warning that abscesses should be drained early and may need to be drained repeatedly.

The investigators said to start empiric antibiotic treatment against both methicillin-susceptible and methicillin-resistant bacterial strains. A 6-week course of treatment, starting with parenteral administration and followed by oral antibiotics against susceptible isolates, is usually adequate, they said. Eight children in the retrospective study were treated with vancomycin and clindamycin.

The Alabama Experience

Dr. Gilbert and his colleagues found 156 cases of culture-proven S. aureus infections when they searched community-acquired septic arthritis or osteomyelitis cases from 2001 to 2007. Of these, 66 cases (42%) were methicillin resistant, including 8 cases of multifocal musculoskeletal infection. In comparison, only 1 child among 90 with methicillin-sensitive infection was affected at more than one site—bringing the total number of multifocal musculoskeletal S. aureus infections to 9.

The number of multifocal infections doubled from three during 2001–2004 to six during 2005–2007. The number of sites also increased from 2–3 during the early period to 2–7 (average 3.8) during the later years.

Serious complications became more common over time as well. One child had bacteremia and none had septic emboli in the early multifocal group. Among the multifocal cases after 2004, four children presented with bacteremia and all six children had septic emboli. Dr. Gilbert said that he now routinely samples all high-risk joints, such as the hips, and any joints with obvious swelling.

Several 'had signs of infection in a knee or ankle for a few days, and it took them a while to get appropriate treatment.' DR. GILBERT

SCOTTSDALE, ARIZ. – Before traveling from California to South Africa, Dr. Alon Y. Avidan prepared for the time change by spending afternoons in his office, out of the sun. After he arrived in South Africa, he awoke between 5 a.m. and 7 a.m. every morning and took a walk for an hour or more in bright sunlight.

“In a few days, I was on South African time,” he told those attending a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Light therapy can be highly effective in correcting jet lag and other circadian rhythm disorders, according to Dr. Avidan, medical director of the University of California, Los Angeles, neurology clinic and associate director of UCLA's sleep disorders center.

Melatonin, a dietary supplement with no approved medical indications, is another useful treatment when delayed sleep is a problem, he said, and ramelteon (Rozerem) shows promise. Although ramelteon is approved only for insomnia, Dr. Avidan said he prescribes it off label to patients with the type of circadian rhythm disorder that causes night owls to complain they can't fall asleep at normal bedtimes or wake up early in the morning.

Often they are tired all day, but not at night, with detriment to their quality of life. “Circadian-related disruption leads to insomnia, hypersomnia, or both,” he said, and it can cause impairment of social, occupational, or other areas of functioning.

Sunlight is the most powerful external time cue for regulating and synchronizing the body's circadian rhythms with the environment, Dr. Avidan said. It promotes wakefulness as input from the retina goes to the suprachiasmatic nucleus (SCN) of the hypothalamus, which contains a circadian pacemaker.

To opposite ends, the pineal gland releases melatonin in response to darkness. Melatonin promotes sleep, but levels of it decrease with aging. Compensating with the dietary supplement has been shown to help advance the circadian clock, according to Dr. Avidan.

For patients with delayed sleep phase, he recommended exposure to bright light–as much as 10,000 amps–in the early morning and taking 0.5 mg of melatonin 5–7 hours before the patient's habitual sleep time, or 12–14 hours before the time a person wishes to awake.

In response to an audience question, Dr. Avidan said several small studies not yet published suggest ramelteon also can advance sleep time. It acts on the melatonin receptors MT1 and MT2, he noted, and described ramelteon as “a true drug.” When using ramelteon off label for a circadian sleep disorder, he prescribes a 4-mg dose (which is half the 8-mg dose approved for insomnia).

Advanced sleep-phase disorder is often seen in poorly lit nursing homes, according to Dr. Avidan. People become sleepy very early in the evening, which causes them to go to bed before 8 p.m. and wake, still sleepy, as early as 3 a.m. or 4 a.m. To delay sleep time and wake time, he recommended exposure to bright lights from 7 p.m. to 9 p.m., but not melatonin because–in addition to promoting sleep–it can exacerbate coronary artery disease in some patients.

Irregular sleep-wake patterns also are seen in nursing homes, he noted. In these cases, although residents accumulate normal sleep time for their age, they do so in three or more irregular periods of sleep. Low doses of melatonin did not help in a multicenter study with Alzheimer's disease patients, according to Dr. Avidan, but 10-mg doses produced a trend toward improvement.

For patients whose weariness is related to working night shifts, Dr. Avidan suggested having the patients align circadian rhythms by wearing dark glasses in the morning, keeping the bedroom dark, going to bed soon after the night shift, and seeking exposure to bright light while working. Other possible interventions include stimulants such as caffeine and modafinil (approved for excessive sleepiness caused by shift work), short-acting hypnotics for insomnia, and melatonin to improve duration of daytime sleep, although it has shown little impact on alertness during night shifts.

Finally, the direction of travel can affect the presentation and treatment of jet lag. People traveling east across two or more time zones will have difficulty falling asleep, whereas those traveling west may struggle to maintain sleep.

In both cases, he said, exposure to and avoidance of light at appropriate times can be “very, very effective.” People traveling west should seek morning light at the new location and avoid exposure to light in the evening. When traveling east, they should do the opposite. “Avoid light in the early morning, and get as much light as possible in the afternoon/early evening,” Dr. Avidan said.

He said it would be advisable to avoid excessive use of caffeine and alcohol in either direction and added that slow-release caffeine has been shown to improve daytime alertness, and melatonin has been shown to foster sleep after an eastbound flight. For specific recommendations geared to time zones of departure and arrival, he recommended using the jet lag calculator in the travel clinic section of www.fleetstreetclinic.com

Dr. Avidan disclosed receiving a consultant fee and serving on the speakers bureau and advisory committee of Takeda Pharmaceuticals, which sells ramelteon in North America. He also listed relationships with Sepracor Inc., GlaxoSmithKline, and Boehringer Ingelheim.

SCOTTSDALE, ARIZ. – Before traveling from California to South Africa, Dr. Alon Y. Avidan prepared for the time change by spending afternoons in his office, out of the sun. After he arrived in South Africa, he awoke between 5 a.m. and 7 a.m. every morning and took a walk for an hour or more in bright sunlight.

“In a few days, I was on South African time,” he told those attending a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Light therapy can be highly effective in correcting jet lag and other circadian rhythm disorders, according to Dr. Avidan, medical director of the University of California, Los Angeles, neurology clinic and associate director of UCLA's sleep disorders center.

Melatonin, a dietary supplement with no approved medical indications, is another useful treatment when delayed sleep is a problem, he said, and ramelteon (Rozerem) shows promise. Although ramelteon is approved only for insomnia, Dr. Avidan said he prescribes it off label to patients with the type of circadian rhythm disorder that causes night owls to complain they can't fall asleep at normal bedtimes or wake up early in the morning.

Often they are tired all day, but not at night, with detriment to their quality of life. “Circadian-related disruption leads to insomnia, hypersomnia, or both,” he said, and it can cause impairment of social, occupational, or other areas of functioning.

Sunlight is the most powerful external time cue for regulating and synchronizing the body's circadian rhythms with the environment, Dr. Avidan said. It promotes wakefulness as input from the retina goes to the suprachiasmatic nucleus (SCN) of the hypothalamus, which contains a circadian pacemaker.

To opposite ends, the pineal gland releases melatonin in response to darkness. Melatonin promotes sleep, but levels of it decrease with aging. Compensating with the dietary supplement has been shown to help advance the circadian clock, according to Dr. Avidan.

For patients with delayed sleep phase, he recommended exposure to bright light–as much as 10,000 amps–in the early morning and taking 0.5 mg of melatonin 5–7 hours before the patient's habitual sleep time, or 12–14 hours before the time a person wishes to awake.

In response to an audience question, Dr. Avidan said several small studies not yet published suggest ramelteon also can advance sleep time. It acts on the melatonin receptors MT1 and MT2, he noted, and described ramelteon as “a true drug.” When using ramelteon off label for a circadian sleep disorder, he prescribes a 4-mg dose (which is half the 8-mg dose approved for insomnia).

Advanced sleep-phase disorder is often seen in poorly lit nursing homes, according to Dr. Avidan. People become sleepy very early in the evening, which causes them to go to bed before 8 p.m. and wake, still sleepy, as early as 3 a.m. or 4 a.m. To delay sleep time and wake time, he recommended exposure to bright lights from 7 p.m. to 9 p.m., but not melatonin because–in addition to promoting sleep–it can exacerbate coronary artery disease in some patients.

Irregular sleep-wake patterns also are seen in nursing homes, he noted. In these cases, although residents accumulate normal sleep time for their age, they do so in three or more irregular periods of sleep. Low doses of melatonin did not help in a multicenter study with Alzheimer's disease patients, according to Dr. Avidan, but 10-mg doses produced a trend toward improvement.

For patients whose weariness is related to working night shifts, Dr. Avidan suggested having the patients align circadian rhythms by wearing dark glasses in the morning, keeping the bedroom dark, going to bed soon after the night shift, and seeking exposure to bright light while working. Other possible interventions include stimulants such as caffeine and modafinil (approved for excessive sleepiness caused by shift work), short-acting hypnotics for insomnia, and melatonin to improve duration of daytime sleep, although it has shown little impact on alertness during night shifts.

Finally, the direction of travel can affect the presentation and treatment of jet lag. People traveling east across two or more time zones will have difficulty falling asleep, whereas those traveling west may struggle to maintain sleep.

In both cases, he said, exposure to and avoidance of light at appropriate times can be “very, very effective.” People traveling west should seek morning light at the new location and avoid exposure to light in the evening. When traveling east, they should do the opposite. “Avoid light in the early morning, and get as much light as possible in the afternoon/early evening,” Dr. Avidan said.

He said it would be advisable to avoid excessive use of caffeine and alcohol in either direction and added that slow-release caffeine has been shown to improve daytime alertness, and melatonin has been shown to foster sleep after an eastbound flight. For specific recommendations geared to time zones of departure and arrival, he recommended using the jet lag calculator in the travel clinic section of www.fleetstreetclinic.com

Dr. Avidan disclosed receiving a consultant fee and serving on the speakers bureau and advisory committee of Takeda Pharmaceuticals, which sells ramelteon in North America. He also listed relationships with Sepracor Inc., GlaxoSmithKline, and Boehringer Ingelheim.

SCOTTSDALE, ARIZ. – Before traveling from California to South Africa, Dr. Alon Y. Avidan prepared for the time change by spending afternoons in his office, out of the sun. After he arrived in South Africa, he awoke between 5 a.m. and 7 a.m. every morning and took a walk for an hour or more in bright sunlight.

“In a few days, I was on South African time,” he told those attending a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Light therapy can be highly effective in correcting jet lag and other circadian rhythm disorders, according to Dr. Avidan, medical director of the University of California, Los Angeles, neurology clinic and associate director of UCLA's sleep disorders center.

Melatonin, a dietary supplement with no approved medical indications, is another useful treatment when delayed sleep is a problem, he said, and ramelteon (Rozerem) shows promise. Although ramelteon is approved only for insomnia, Dr. Avidan said he prescribes it off label to patients with the type of circadian rhythm disorder that causes night owls to complain they can't fall asleep at normal bedtimes or wake up early in the morning.

Often they are tired all day, but not at night, with detriment to their quality of life. “Circadian-related disruption leads to insomnia, hypersomnia, or both,” he said, and it can cause impairment of social, occupational, or other areas of functioning.

Sunlight is the most powerful external time cue for regulating and synchronizing the body's circadian rhythms with the environment, Dr. Avidan said. It promotes wakefulness as input from the retina goes to the suprachiasmatic nucleus (SCN) of the hypothalamus, which contains a circadian pacemaker.

To opposite ends, the pineal gland releases melatonin in response to darkness. Melatonin promotes sleep, but levels of it decrease with aging. Compensating with the dietary supplement has been shown to help advance the circadian clock, according to Dr. Avidan.

For patients with delayed sleep phase, he recommended exposure to bright light–as much as 10,000 amps–in the early morning and taking 0.5 mg of melatonin 5–7 hours before the patient's habitual sleep time, or 12–14 hours before the time a person wishes to awake.

In response to an audience question, Dr. Avidan said several small studies not yet published suggest ramelteon also can advance sleep time. It acts on the melatonin receptors MT1 and MT2, he noted, and described ramelteon as “a true drug.” When using ramelteon off label for a circadian sleep disorder, he prescribes a 4-mg dose (which is half the 8-mg dose approved for insomnia).

Advanced sleep-phase disorder is often seen in poorly lit nursing homes, according to Dr. Avidan. People become sleepy very early in the evening, which causes them to go to bed before 8 p.m. and wake, still sleepy, as early as 3 a.m. or 4 a.m. To delay sleep time and wake time, he recommended exposure to bright lights from 7 p.m. to 9 p.m., but not melatonin because–in addition to promoting sleep–it can exacerbate coronary artery disease in some patients.

Irregular sleep-wake patterns also are seen in nursing homes, he noted. In these cases, although residents accumulate normal sleep time for their age, they do so in three or more irregular periods of sleep. Low doses of melatonin did not help in a multicenter study with Alzheimer's disease patients, according to Dr. Avidan, but 10-mg doses produced a trend toward improvement.

For patients whose weariness is related to working night shifts, Dr. Avidan suggested having the patients align circadian rhythms by wearing dark glasses in the morning, keeping the bedroom dark, going to bed soon after the night shift, and seeking exposure to bright light while working. Other possible interventions include stimulants such as caffeine and modafinil (approved for excessive sleepiness caused by shift work), short-acting hypnotics for insomnia, and melatonin to improve duration of daytime sleep, although it has shown little impact on alertness during night shifts.

Finally, the direction of travel can affect the presentation and treatment of jet lag. People traveling east across two or more time zones will have difficulty falling asleep, whereas those traveling west may struggle to maintain sleep.

In both cases, he said, exposure to and avoidance of light at appropriate times can be “very, very effective.” People traveling west should seek morning light at the new location and avoid exposure to light in the evening. When traveling east, they should do the opposite. “Avoid light in the early morning, and get as much light as possible in the afternoon/early evening,” Dr. Avidan said.

He said it would be advisable to avoid excessive use of caffeine and alcohol in either direction and added that slow-release caffeine has been shown to improve daytime alertness, and melatonin has been shown to foster sleep after an eastbound flight. For specific recommendations geared to time zones of departure and arrival, he recommended using the jet lag calculator in the travel clinic section of www.fleetstreetclinic.com

Dr. Avidan disclosed receiving a consultant fee and serving on the speakers bureau and advisory committee of Takeda Pharmaceuticals, which sells ramelteon in North America. He also listed relationships with Sepracor Inc., GlaxoSmithKline, and Boehringer Ingelheim.

Abnormal Pap tests and cervical procedures have already declined markedly among young women who were vaccinated against the human papillomavirus in three pivotal clinical trials, according to data presented in Tampa at the annual meeting of the Society of Gynecologic Oncologists.

Comparison of 4,696 vaccinated women with 4,759 women in placebo groups showed reductions of 19% in colposcopy, 22% in cervical biopsy, and 42% in excisional therapy at an average follow-up of 3.3 years after the first dose of the quadrivalent vaccine (Gardisil/Silgard) against human papillomavirus (HPV) types 6, 11, 16, and 18.

Beyond the immediate benefit in reduced anxiety for women and costs for insurers, the results suggest the vaccine can deliver on the promise of preventing cervical cancer, investigator Dr. Warner K. Huh said in an interview. At least 20 years of follow-up are needed to see the impact of HPV prevention on cervical cancer. He characterized the disease as extremely rare in women under age 35 years and infrequent among women of all ages.

“Very few of us can identify with cervical cancer, but almost every woman in the United States can identify with an abnormal Pap smear,” said Dr. Huh of the University of Alabama, Birmingham. “In the course of a lifetime, one in three women in the United States will have an abnormal Pap smear.”

He estimated the cost of screening of cervical abnormalities as more than $2 billion a year in the United States. When the cost of treating cervical abnormalities is added, the bill comes to about $4 billion, according to the society.

The end-of-study data reported came from three large efficacy trials sponsored by Merck & Co., maker of the vaccine. All told, the studies randomized 18,150 women aged 16–26 years to the vaccine or a placebo. Participants had cervicovaginal sampling and Pap smears on their first day in the studies and were followed with Pap smears every 6–12 months for up to 48 months. Median follow-up was 4 years from day 1.

The analysis of abnormal Pap results covered findings due to any HPV type and not just the targets of the vaccine. Dr. Huh said previous research suggests the vaccine provides some cross-protection though this has not been defined. The comparison of abnormal Pap results included 4,870 vaccinated women and 4,758 women given a placebo.

The most dramatic reduction was 43% in high-grade squamous intraepithelial lesions (HSILs) seen on Pap smears. Although the drop was substantial, the numbers were small, with only 41 cases in the placebo group and 24 in vaccinated women. Low-grade squamous intraepithelial lesions (LSIL) declined by 14%, occurring in 864 vaccinated women, compared with 1,000 women on placebo.

Other reductions in abnormal Pap tests included:

▸ A drop of 16% in atypical squamous cells of undetermined significance that were high-risk positive (meaning positive for one of the 13 cancer-causing HPV types for which the sample was tested), LSIL, or worse (1,062 women in the vaccine group vs. 1,226 on placebo).

▸ A decrease of 23% in atypical squamous cells of undetermined significance that were high-risk positive (285 vs. 359).

▸ A drop of 35% in atypical squamous cells that couldn't exclude HSIL (59 vs. 89).

Absolute numbers in the data comparing procedures showed: colposcopy in 869 vaccinated women, compared with 1,077 on placebo (19% reduction); biopsy in 741 vaccinated women, compared with 950 on placebo (22% reduction), and definitive therapy in 132 vaccinated women, compared with 230 on placebo (42% reduction).

Dr. Huh disclosed relationships with Merck, including being a consultant and speaker and receiving a research grant.

ELSEVIER GLOBAL MEDICAL NEWS

Abnormal Pap tests and cervical procedures have already declined markedly among young women who were vaccinated against the human papillomavirus in three pivotal clinical trials, according to data presented in Tampa at the annual meeting of the Society of Gynecologic Oncologists.

Comparison of 4,696 vaccinated women with 4,759 women in placebo groups showed reductions of 19% in colposcopy, 22% in cervical biopsy, and 42% in excisional therapy at an average follow-up of 3.3 years after the first dose of the quadrivalent vaccine (Gardisil/Silgard) against human papillomavirus (HPV) types 6, 11, 16, and 18.

Beyond the immediate benefit in reduced anxiety for women and costs for insurers, the results suggest the vaccine can deliver on the promise of preventing cervical cancer, investigator Dr. Warner K. Huh said in an interview. At least 20 years of follow-up are needed to see the impact of HPV prevention on cervical cancer. He characterized the disease as extremely rare in women under age 35 years and infrequent among women of all ages.

“Very few of us can identify with cervical cancer, but almost every woman in the United States can identify with an abnormal Pap smear,” said Dr. Huh of the University of Alabama, Birmingham. “In the course of a lifetime, one in three women in the United States will have an abnormal Pap smear.”

He estimated the cost of screening of cervical abnormalities as more than $2 billion a year in the United States. When the cost of treating cervical abnormalities is added, the bill comes to about $4 billion, according to the society.

The end-of-study data reported came from three large efficacy trials sponsored by Merck & Co., maker of the vaccine. All told, the studies randomized 18,150 women aged 16–26 years to the vaccine or a placebo. Participants had cervicovaginal sampling and Pap smears on their first day in the studies and were followed with Pap smears every 6–12 months for up to 48 months. Median follow-up was 4 years from day 1.

The analysis of abnormal Pap results covered findings due to any HPV type and not just the targets of the vaccine. Dr. Huh said previous research suggests the vaccine provides some cross-protection though this has not been defined. The comparison of abnormal Pap results included 4,870 vaccinated women and 4,758 women given a placebo.

The most dramatic reduction was 43% in high-grade squamous intraepithelial lesions (HSILs) seen on Pap smears. Although the drop was substantial, the numbers were small, with only 41 cases in the placebo group and 24 in vaccinated women. Low-grade squamous intraepithelial lesions (LSIL) declined by 14%, occurring in 864 vaccinated women, compared with 1,000 women on placebo.

Other reductions in abnormal Pap tests included:

▸ A drop of 16% in atypical squamous cells of undetermined significance that were high-risk positive (meaning positive for one of the 13 cancer-causing HPV types for which the sample was tested), LSIL, or worse (1,062 women in the vaccine group vs. 1,226 on placebo).

▸ A decrease of 23% in atypical squamous cells of undetermined significance that were high-risk positive (285 vs. 359).

▸ A drop of 35% in atypical squamous cells that couldn't exclude HSIL (59 vs. 89).

Absolute numbers in the data comparing procedures showed: colposcopy in 869 vaccinated women, compared with 1,077 on placebo (19% reduction); biopsy in 741 vaccinated women, compared with 950 on placebo (22% reduction), and definitive therapy in 132 vaccinated women, compared with 230 on placebo (42% reduction).

Dr. Huh disclosed relationships with Merck, including being a consultant and speaker and receiving a research grant.

ELSEVIER GLOBAL MEDICAL NEWS

Abnormal Pap tests and cervical procedures have already declined markedly among young women who were vaccinated against the human papillomavirus in three pivotal clinical trials, according to data presented in Tampa at the annual meeting of the Society of Gynecologic Oncologists.

Comparison of 4,696 vaccinated women with 4,759 women in placebo groups showed reductions of 19% in colposcopy, 22% in cervical biopsy, and 42% in excisional therapy at an average follow-up of 3.3 years after the first dose of the quadrivalent vaccine (Gardisil/Silgard) against human papillomavirus (HPV) types 6, 11, 16, and 18.

Beyond the immediate benefit in reduced anxiety for women and costs for insurers, the results suggest the vaccine can deliver on the promise of preventing cervical cancer, investigator Dr. Warner K. Huh said in an interview. At least 20 years of follow-up are needed to see the impact of HPV prevention on cervical cancer. He characterized the disease as extremely rare in women under age 35 years and infrequent among women of all ages.

“Very few of us can identify with cervical cancer, but almost every woman in the United States can identify with an abnormal Pap smear,” said Dr. Huh of the University of Alabama, Birmingham. “In the course of a lifetime, one in three women in the United States will have an abnormal Pap smear.”

He estimated the cost of screening of cervical abnormalities as more than $2 billion a year in the United States. When the cost of treating cervical abnormalities is added, the bill comes to about $4 billion, according to the society.

The end-of-study data reported came from three large efficacy trials sponsored by Merck & Co., maker of the vaccine. All told, the studies randomized 18,150 women aged 16–26 years to the vaccine or a placebo. Participants had cervicovaginal sampling and Pap smears on their first day in the studies and were followed with Pap smears every 6–12 months for up to 48 months. Median follow-up was 4 years from day 1.

The analysis of abnormal Pap results covered findings due to any HPV type and not just the targets of the vaccine. Dr. Huh said previous research suggests the vaccine provides some cross-protection though this has not been defined. The comparison of abnormal Pap results included 4,870 vaccinated women and 4,758 women given a placebo.

The most dramatic reduction was 43% in high-grade squamous intraepithelial lesions (HSILs) seen on Pap smears. Although the drop was substantial, the numbers were small, with only 41 cases in the placebo group and 24 in vaccinated women. Low-grade squamous intraepithelial lesions (LSIL) declined by 14%, occurring in 864 vaccinated women, compared with 1,000 women on placebo.

Other reductions in abnormal Pap tests included:

▸ A drop of 16% in atypical squamous cells of undetermined significance that were high-risk positive (meaning positive for one of the 13 cancer-causing HPV types for which the sample was tested), LSIL, or worse (1,062 women in the vaccine group vs. 1,226 on placebo).

▸ A decrease of 23% in atypical squamous cells of undetermined significance that were high-risk positive (285 vs. 359).

▸ A drop of 35% in atypical squamous cells that couldn't exclude HSIL (59 vs. 89).

Absolute numbers in the data comparing procedures showed: colposcopy in 869 vaccinated women, compared with 1,077 on placebo (19% reduction); biopsy in 741 vaccinated women, compared with 950 on placebo (22% reduction), and definitive therapy in 132 vaccinated women, compared with 230 on placebo (42% reduction).

Dr. Huh disclosed relationships with Merck, including being a consultant and speaker and receiving a research grant.

ELSEVIER GLOBAL MEDICAL NEWS

SCOTTSDALE, ARIZ. – Even though sleepwalking, night terrors, and other parasomnias are usually benign and do not call for specific interventions, Dr. Teofilo L. Lee-Chiong Jr. urged that they be thoroughly evaluated in children and adults.

Violent and potentially injurious behavior can endanger the person and/or the person's bed partner, according to Dr. Lee-Chiong, head of the sleep medicine section at National Jewish Medical and Research Center in Denver. A recent patient, for example, walked for 4 hours along a busy interstate highway while fast asleep, Dr. Lee-Chiong said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Another concern, he added, is that a patient with REM sleep behavior disorder could have undiagnosed Parkinson's disease or another neurological disorder. Characteristics of this condition include abnormal behavior during REM sleep, REM sleep without atonia, and the enactment of altered, unpleasant, or violent dreams.

“I believe assessment should be extensive,” Dr. Lee-Chiong said, recommending a comprehensive neurological evaluation with EEG and brain MRI in REM sleep behavior disorder cases.

Even if these tests prove negative, he urged that the patient be closely monitored for years afterward in case a neurological disorder is late in emerging.

Dr. Lee-Chiong defined parasomnias as undesirable physical phenomena or behaviors that appear “alongside sleep,” but are not associated with more common complaints such as excess sleepiness or insomnia. “We all seem to know what it is, but deep down we know very little,” he said, adding afterward in an interview, “If you take [posttraumatic stress disorder] away, there really is no psychopathology that predicts the development of parasomnias.”

A variety of factors make evaluation difficult, according to Dr. Lee-Chiong. Patients are unaware of some parasomnias. Descriptions are often inaccurate or misleading. The clinician rarely sees the parasomnia. If it is not related to sleep architecture, then polysomnography may not be useful. Moreover, a single negative test does not rule out infrequent events.

Polysomnography is indicated when an underlying seizure disorder is suspected, someone has been injured, the case has medical-legal implications, or the person presents with REM sleep behavior disorder, according to Dr. Lee-Chiong. EEG electrodes should be used if seizures are a possibility. In REM sleep behavior disorder cases, he also recommends EMG monitoring of the upper extremities. Often four to six studies are required before a diagnosis can be made, he advised, and technicians need to be trained to recognize subtle features.

Dr. Lee-Chiong characterized sleepwalking, sleep terrors, and confusional arousals as disorders of arousal that usually occur in non-REM sleep during the first third of the night. These are four times as common in childhood, he said, with a prevalence of 16% vs. 4% in adults. Febrile illness in children and medications in the elderly are among the predisposing factors, though sleep terrors are uncommon in older people.

Genetics appears to play a role in sleepwalking, according to Dr. Lee-Chiong. Prevalence is 45% if one parent engaged in sleepwalking, and 60% if both parents had the condition. In addition, the DQB1*0501 allele is more common among sleepwalkers.

Treatments can range from proper sleep hygiene and relaxation techniques to pharmacologic agents, including low-dose benzodiazepines, SSRIs, tricyclic antidepressants, and trazodone.

In cases of confusional arousals (waking with disorientation, inappropriate behavior, or inability to be consoled), Dr. Lee-Chiong suggested attempting to break the cycle by waking a child about 15 minutes before the time these usually occur.

REM sleep parasomnias typically occur during early morning hours, he said. Unlike sleepwalkers, people with REM sleep behavior disorder usually keep their eyes closed and can recall their dreams afterward. The condition is more common in men and can include screaming, punching, kicking, jumping, and running. “True intent to harm” should be considered in the differential diagnosis.

A host of medications–for example, alcohol, amphetamines, anticholinergics, antidepressants other than bupropion, biperiden, cocaine, sedative-hypnotics, and selegiline–might precipitate REM sleep behavior disorder, as can withdrawal from alcohol, hypnotic agents, and REM suppressants.

Deciding whether and how to treat can be problematic, according to Dr. Lee-Chiong. Daily medication might be riskier than infrequent parasomnias. Clonazepam has been successful in 87% of cases, he said.

Even if tests prove negative, it makes sense to closely monitor the patient for years afterward. DR. LEE-CHIONG

Tips for Making Bedrooms Safer

Removing weapons such as guns and knives from the bedroom is a given when people present with parasomnias that put them and their bed partners in harm's way.

Yet Dr. Teofilo L. Lee-Chiong Jr. said in an interview that he knows of no cases in which these weapons have caused injury during a parasomnia. Other, less obvious changes are at least as important, he said, offering the following recommendations for a safe bedroom:

▸ Keep the floor very clean. There should be no object on the floor that could cause a person to slide or trip.

▸ Make sure nothing breakable is within reach of the person. Glasses and mirrors might have to be removed from the bedroom.

▸ Exclude sharp objects, including pens.

▸ Pad sharp edges of bedroom furniture.

▸ Close the bathroom door–add a barrier, if necessary–to keep out a person having a parasomnia. The floor is harder, and fixtures can create a dangerous obstacle course for a person who is not fully awake.

▸ Sleep on the first floor if possible. Stairs and upper story windows are hazards.

▸ Use heavy curtains to prevent cuts to the hand and forearm, if a person strikes out and breaks the glass.

SCOTTSDALE, ARIZ. – Even though sleepwalking, night terrors, and other parasomnias are usually benign and do not call for specific interventions, Dr. Teofilo L. Lee-Chiong Jr. urged that they be thoroughly evaluated in children and adults.

Violent and potentially injurious behavior can endanger the person and/or the person's bed partner, according to Dr. Lee-Chiong, head of the sleep medicine section at National Jewish Medical and Research Center in Denver. A recent patient, for example, walked for 4 hours along a busy interstate highway while fast asleep, Dr. Lee-Chiong said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Another concern, he added, is that a patient with REM sleep behavior disorder could have undiagnosed Parkinson's disease or another neurological disorder. Characteristics of this condition include abnormal behavior during REM sleep, REM sleep without atonia, and the enactment of altered, unpleasant, or violent dreams.

“I believe assessment should be extensive,” Dr. Lee-Chiong said, recommending a comprehensive neurological evaluation with EEG and brain MRI in REM sleep behavior disorder cases.

Even if these tests prove negative, he urged that the patient be closely monitored for years afterward in case a neurological disorder is late in emerging.

Dr. Lee-Chiong defined parasomnias as undesirable physical phenomena or behaviors that appear “alongside sleep,” but are not associated with more common complaints such as excess sleepiness or insomnia. “We all seem to know what it is, but deep down we know very little,” he said, adding afterward in an interview, “If you take [posttraumatic stress disorder] away, there really is no psychopathology that predicts the development of parasomnias.”

A variety of factors make evaluation difficult, according to Dr. Lee-Chiong. Patients are unaware of some parasomnias. Descriptions are often inaccurate or misleading. The clinician rarely sees the parasomnia. If it is not related to sleep architecture, then polysomnography may not be useful. Moreover, a single negative test does not rule out infrequent events.

Polysomnography is indicated when an underlying seizure disorder is suspected, someone has been injured, the case has medical-legal implications, or the person presents with REM sleep behavior disorder, according to Dr. Lee-Chiong. EEG electrodes should be used if seizures are a possibility. In REM sleep behavior disorder cases, he also recommends EMG monitoring of the upper extremities. Often four to six studies are required before a diagnosis can be made, he advised, and technicians need to be trained to recognize subtle features.

Dr. Lee-Chiong characterized sleepwalking, sleep terrors, and confusional arousals as disorders of arousal that usually occur in non-REM sleep during the first third of the night. These are four times as common in childhood, he said, with a prevalence of 16% vs. 4% in adults. Febrile illness in children and medications in the elderly are among the predisposing factors, though sleep terrors are uncommon in older people.

Genetics appears to play a role in sleepwalking, according to Dr. Lee-Chiong. Prevalence is 45% if one parent engaged in sleepwalking, and 60% if both parents had the condition. In addition, the DQB1*0501 allele is more common among sleepwalkers.

Treatments can range from proper sleep hygiene and relaxation techniques to pharmacologic agents, including low-dose benzodiazepines, SSRIs, tricyclic antidepressants, and trazodone.

In cases of confusional arousals (waking with disorientation, inappropriate behavior, or inability to be consoled), Dr. Lee-Chiong suggested attempting to break the cycle by waking a child about 15 minutes before the time these usually occur.

REM sleep parasomnias typically occur during early morning hours, he said. Unlike sleepwalkers, people with REM sleep behavior disorder usually keep their eyes closed and can recall their dreams afterward. The condition is more common in men and can include screaming, punching, kicking, jumping, and running. “True intent to harm” should be considered in the differential diagnosis.

A host of medications–for example, alcohol, amphetamines, anticholinergics, antidepressants other than bupropion, biperiden, cocaine, sedative-hypnotics, and selegiline–might precipitate REM sleep behavior disorder, as can withdrawal from alcohol, hypnotic agents, and REM suppressants.

Deciding whether and how to treat can be problematic, according to Dr. Lee-Chiong. Daily medication might be riskier than infrequent parasomnias. Clonazepam has been successful in 87% of cases, he said.

Even if tests prove negative, it makes sense to closely monitor the patient for years afterward. DR. LEE-CHIONG

Tips for Making Bedrooms Safer

Removing weapons such as guns and knives from the bedroom is a given when people present with parasomnias that put them and their bed partners in harm's way.

Yet Dr. Teofilo L. Lee-Chiong Jr. said in an interview that he knows of no cases in which these weapons have caused injury during a parasomnia. Other, less obvious changes are at least as important, he said, offering the following recommendations for a safe bedroom:

▸ Keep the floor very clean. There should be no object on the floor that could cause a person to slide or trip.

▸ Make sure nothing breakable is within reach of the person. Glasses and mirrors might have to be removed from the bedroom.

▸ Exclude sharp objects, including pens.

▸ Pad sharp edges of bedroom furniture.

▸ Close the bathroom door–add a barrier, if necessary–to keep out a person having a parasomnia. The floor is harder, and fixtures can create a dangerous obstacle course for a person who is not fully awake.

▸ Sleep on the first floor if possible. Stairs and upper story windows are hazards.

▸ Use heavy curtains to prevent cuts to the hand and forearm, if a person strikes out and breaks the glass.

SCOTTSDALE, ARIZ. – Even though sleepwalking, night terrors, and other parasomnias are usually benign and do not call for specific interventions, Dr. Teofilo L. Lee-Chiong Jr. urged that they be thoroughly evaluated in children and adults.

Violent and potentially injurious behavior can endanger the person and/or the person's bed partner, according to Dr. Lee-Chiong, head of the sleep medicine section at National Jewish Medical and Research Center in Denver. A recent patient, for example, walked for 4 hours along a busy interstate highway while fast asleep, Dr. Lee-Chiong said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Another concern, he added, is that a patient with REM sleep behavior disorder could have undiagnosed Parkinson's disease or another neurological disorder. Characteristics of this condition include abnormal behavior during REM sleep, REM sleep without atonia, and the enactment of altered, unpleasant, or violent dreams.

“I believe assessment should be extensive,” Dr. Lee-Chiong said, recommending a comprehensive neurological evaluation with EEG and brain MRI in REM sleep behavior disorder cases.

Even if these tests prove negative, he urged that the patient be closely monitored for years afterward in case a neurological disorder is late in emerging.

Dr. Lee-Chiong defined parasomnias as undesirable physical phenomena or behaviors that appear “alongside sleep,” but are not associated with more common complaints such as excess sleepiness or insomnia. “We all seem to know what it is, but deep down we know very little,” he said, adding afterward in an interview, “If you take [posttraumatic stress disorder] away, there really is no psychopathology that predicts the development of parasomnias.”

A variety of factors make evaluation difficult, according to Dr. Lee-Chiong. Patients are unaware of some parasomnias. Descriptions are often inaccurate or misleading. The clinician rarely sees the parasomnia. If it is not related to sleep architecture, then polysomnography may not be useful. Moreover, a single negative test does not rule out infrequent events.

Polysomnography is indicated when an underlying seizure disorder is suspected, someone has been injured, the case has medical-legal implications, or the person presents with REM sleep behavior disorder, according to Dr. Lee-Chiong. EEG electrodes should be used if seizures are a possibility. In REM sleep behavior disorder cases, he also recommends EMG monitoring of the upper extremities. Often four to six studies are required before a diagnosis can be made, he advised, and technicians need to be trained to recognize subtle features.

Dr. Lee-Chiong characterized sleepwalking, sleep terrors, and confusional arousals as disorders of arousal that usually occur in non-REM sleep during the first third of the night. These are four times as common in childhood, he said, with a prevalence of 16% vs. 4% in adults. Febrile illness in children and medications in the elderly are among the predisposing factors, though sleep terrors are uncommon in older people.

Genetics appears to play a role in sleepwalking, according to Dr. Lee-Chiong. Prevalence is 45% if one parent engaged in sleepwalking, and 60% if both parents had the condition. In addition, the DQB1*0501 allele is more common among sleepwalkers.

Treatments can range from proper sleep hygiene and relaxation techniques to pharmacologic agents, including low-dose benzodiazepines, SSRIs, tricyclic antidepressants, and trazodone.

In cases of confusional arousals (waking with disorientation, inappropriate behavior, or inability to be consoled), Dr. Lee-Chiong suggested attempting to break the cycle by waking a child about 15 minutes before the time these usually occur.

REM sleep parasomnias typically occur during early morning hours, he said. Unlike sleepwalkers, people with REM sleep behavior disorder usually keep their eyes closed and can recall their dreams afterward. The condition is more common in men and can include screaming, punching, kicking, jumping, and running. “True intent to harm” should be considered in the differential diagnosis.

A host of medications–for example, alcohol, amphetamines, anticholinergics, antidepressants other than bupropion, biperiden, cocaine, sedative-hypnotics, and selegiline–might precipitate REM sleep behavior disorder, as can withdrawal from alcohol, hypnotic agents, and REM suppressants.

Deciding whether and how to treat can be problematic, according to Dr. Lee-Chiong. Daily medication might be riskier than infrequent parasomnias. Clonazepam has been successful in 87% of cases, he said.

Even if tests prove negative, it makes sense to closely monitor the patient for years afterward. DR. LEE-CHIONG

Tips for Making Bedrooms Safer

Removing weapons such as guns and knives from the bedroom is a given when people present with parasomnias that put them and their bed partners in harm's way.

Yet Dr. Teofilo L. Lee-Chiong Jr. said in an interview that he knows of no cases in which these weapons have caused injury during a parasomnia. Other, less obvious changes are at least as important, he said, offering the following recommendations for a safe bedroom:

▸ Keep the floor very clean. There should be no object on the floor that could cause a person to slide or trip.

▸ Make sure nothing breakable is within reach of the person. Glasses and mirrors might have to be removed from the bedroom.

▸ Exclude sharp objects, including pens.

▸ Pad sharp edges of bedroom furniture.

▸ Close the bathroom door–add a barrier, if necessary–to keep out a person having a parasomnia. The floor is harder, and fixtures can create a dangerous obstacle course for a person who is not fully awake.

▸ Sleep on the first floor if possible. Stairs and upper story windows are hazards.

▸ Use heavy curtains to prevent cuts to the hand and forearm, if a person strikes out and breaks the glass.

Abnormal Pap tests and cervical procedures have already declined markedly among young women who were vaccinated against the human papillomavirus in three pivotal clinical trials, according to data presented in Tampa at the annual meeting of the Society of Gynecologic Oncologists.

Comparison of 4,696 vaccinated women with 4,759 women in placebo groups showed reductions of 19% in colposcopy, 22% in cervical biopsy, and 42% in excisional therapy at an average follow-up of 3.3 years after the first dose of the quadrivalent vaccine (Gardisil/Silgard) against human papillomavirus (HPV) types 6, 11, 16, and 18.

Beyond the immediate benefit in reduced anxiety for women and costs for insurers, the results suggest the vaccine can deliver on the promise of preventing cervical cancer, investigator Dr. Warner K. Huh said in an interview. At least 20 years of follow-up are needed to see the impact of HPV prevention on cervical cancer.

"In the course of a lifetime, one in three women in the United States will have an abnormal Pap smear," said Dr. Huh of the University of Alabama, Birmingham.

He estimated the cost of screening of cervical abnormalities as more than $2 billion a year in the United States. When the cost of treating cervical abnormalities is added, the bill comes to about $4 billion, according to the SGO.

The end-of-study data reported came from three large efficacy trials sponsored by Merck & Co., maker of the vaccine. All told, the studies randomized 18,150 women aged 16–26 years to the vaccine or a placebo. Participants had cervicovaginal sampling and Pap smears on their first day in the studies and were followed with Pap smears every 6–12 months for up to 48 months. Median follow-up was 4 years from day 1.

The analysis of abnormal Pap results covered findings due to any HPV type and not just the targets of the vaccine. Dr. Huh said previous research suggests the vaccine provides some cross-protection though this has not been defined. The comparison of abnormal Pap results included 4,870 vaccinated women and 4,758 women given a placebo.

The most dramatic reduction was 43% in high-grade squamous intraepithelial lesions (HSILs) seen on Pap smears. Although the drop was substantial, the numbers were small with only 41 cases in the placebo group and 24 among vaccinated women. Low-grade squamous intraepithelial lesions (LSIL) declined by 14%, occurring in 864 vaccinated women vs. 1,000 women on placebo. Other reductions in abnormal Pap tests included:

▸ A drop of 16% in atypical squamous cells of undetermined significance that were high-risk positive (meaning positive for one of the 13 cancer-causing HPV types for which the sample was tested), LSIL, or worse (1,062 women in the vaccine group vs. 1,226 on placebo).

▸ A decrease of 23% in atypical squamous cells of undetermined significance that were high-risk positive (285 vs. 359).

▸ A decrease of 35% in atypical squamous cells that could not exclude HSIL (59 vs. 89).

Absolute numbers in the data comparing procedures showed: colposcopy in 869 vaccinated women vs. 1,077 on placebo (a 19% reduction); biopsy in 741 vaccinated women vs. 950 on placebo (a 22% reduction), and definitive therapy in 132 vaccinated women vs. 230 on placebo (a 42% reduction).

He disclosed relationships with Merck, including being a consultant and speaker and receiving a research grant.

ELSEVIER GLOBAL MEDICAL NEWS

Abnormal Pap tests and cervical procedures have already declined markedly among young women who were vaccinated against the human papillomavirus in three pivotal clinical trials, according to data presented in Tampa at the annual meeting of the Society of Gynecologic Oncologists.

Comparison of 4,696 vaccinated women with 4,759 women in placebo groups showed reductions of 19% in colposcopy, 22% in cervical biopsy, and 42% in excisional therapy at an average follow-up of 3.3 years after the first dose of the quadrivalent vaccine (Gardisil/Silgard) against human papillomavirus (HPV) types 6, 11, 16, and 18.

Beyond the immediate benefit in reduced anxiety for women and costs for insurers, the results suggest the vaccine can deliver on the promise of preventing cervical cancer, investigator Dr. Warner K. Huh said in an interview. At least 20 years of follow-up are needed to see the impact of HPV prevention on cervical cancer.

"In the course of a lifetime, one in three women in the United States will have an abnormal Pap smear," said Dr. Huh of the University of Alabama, Birmingham.

He estimated the cost of screening of cervical abnormalities as more than $2 billion a year in the United States. When the cost of treating cervical abnormalities is added, the bill comes to about $4 billion, according to the SGO.

The end-of-study data reported came from three large efficacy trials sponsored by Merck & Co., maker of the vaccine. All told, the studies randomized 18,150 women aged 16–26 years to the vaccine or a placebo. Participants had cervicovaginal sampling and Pap smears on their first day in the studies and were followed with Pap smears every 6–12 months for up to 48 months. Median follow-up was 4 years from day 1.

The analysis of abnormal Pap results covered findings due to any HPV type and not just the targets of the vaccine. Dr. Huh said previous research suggests the vaccine provides some cross-protection though this has not been defined. The comparison of abnormal Pap results included 4,870 vaccinated women and 4,758 women given a placebo.

The most dramatic reduction was 43% in high-grade squamous intraepithelial lesions (HSILs) seen on Pap smears. Although the drop was substantial, the numbers were small with only 41 cases in the placebo group and 24 among vaccinated women. Low-grade squamous intraepithelial lesions (LSIL) declined by 14%, occurring in 864 vaccinated women vs. 1,000 women on placebo. Other reductions in abnormal Pap tests included:

▸ A drop of 16% in atypical squamous cells of undetermined significance that were high-risk positive (meaning positive for one of the 13 cancer-causing HPV types for which the sample was tested), LSIL, or worse (1,062 women in the vaccine group vs. 1,226 on placebo).

▸ A decrease of 23% in atypical squamous cells of undetermined significance that were high-risk positive (285 vs. 359).

▸ A decrease of 35% in atypical squamous cells that could not exclude HSIL (59 vs. 89).

Absolute numbers in the data comparing procedures showed: colposcopy in 869 vaccinated women vs. 1,077 on placebo (a 19% reduction); biopsy in 741 vaccinated women vs. 950 on placebo (a 22% reduction), and definitive therapy in 132 vaccinated women vs. 230 on placebo (a 42% reduction).

He disclosed relationships with Merck, including being a consultant and speaker and receiving a research grant.

ELSEVIER GLOBAL MEDICAL NEWS

Abnormal Pap tests and cervical procedures have already declined markedly among young women who were vaccinated against the human papillomavirus in three pivotal clinical trials, according to data presented in Tampa at the annual meeting of the Society of Gynecologic Oncologists.

Comparison of 4,696 vaccinated women with 4,759 women in placebo groups showed reductions of 19% in colposcopy, 22% in cervical biopsy, and 42% in excisional therapy at an average follow-up of 3.3 years after the first dose of the quadrivalent vaccine (Gardisil/Silgard) against human papillomavirus (HPV) types 6, 11, 16, and 18.

Beyond the immediate benefit in reduced anxiety for women and costs for insurers, the results suggest the vaccine can deliver on the promise of preventing cervical cancer, investigator Dr. Warner K. Huh said in an interview. At least 20 years of follow-up are needed to see the impact of HPV prevention on cervical cancer.

"In the course of a lifetime, one in three women in the United States will have an abnormal Pap smear," said Dr. Huh of the University of Alabama, Birmingham.

He estimated the cost of screening of cervical abnormalities as more than $2 billion a year in the United States. When the cost of treating cervical abnormalities is added, the bill comes to about $4 billion, according to the SGO.

The end-of-study data reported came from three large efficacy trials sponsored by Merck & Co., maker of the vaccine. All told, the studies randomized 18,150 women aged 16–26 years to the vaccine or a placebo. Participants had cervicovaginal sampling and Pap smears on their first day in the studies and were followed with Pap smears every 6–12 months for up to 48 months. Median follow-up was 4 years from day 1.

The analysis of abnormal Pap results covered findings due to any HPV type and not just the targets of the vaccine. Dr. Huh said previous research suggests the vaccine provides some cross-protection though this has not been defined. The comparison of abnormal Pap results included 4,870 vaccinated women and 4,758 women given a placebo.

The most dramatic reduction was 43% in high-grade squamous intraepithelial lesions (HSILs) seen on Pap smears. Although the drop was substantial, the numbers were small with only 41 cases in the placebo group and 24 among vaccinated women. Low-grade squamous intraepithelial lesions (LSIL) declined by 14%, occurring in 864 vaccinated women vs. 1,000 women on placebo. Other reductions in abnormal Pap tests included:

▸ A drop of 16% in atypical squamous cells of undetermined significance that were high-risk positive (meaning positive for one of the 13 cancer-causing HPV types for which the sample was tested), LSIL, or worse (1,062 women in the vaccine group vs. 1,226 on placebo).

▸ A decrease of 23% in atypical squamous cells of undetermined significance that were high-risk positive (285 vs. 359).

▸ A decrease of 35% in atypical squamous cells that could not exclude HSIL (59 vs. 89).

Absolute numbers in the data comparing procedures showed: colposcopy in 869 vaccinated women vs. 1,077 on placebo (a 19% reduction); biopsy in 741 vaccinated women vs. 950 on placebo (a 22% reduction), and definitive therapy in 132 vaccinated women vs. 230 on placebo (a 42% reduction).

He disclosed relationships with Merck, including being a consultant and speaker and receiving a research grant.

ELSEVIER GLOBAL MEDICAL NEWS

LOS ANGELES — Dad had prostate cancer. So did a brother. Does this mean a worse prognosis for the patient?

To answer this, researchers compared rates of freedom from biochemical failure in a retrospective study of 1,738 men treated with low-dose-rate brachytherapy alone or combined with external beam radio- therapy or hormone ablation. A history of prostate cancer in one or more first-degree relatives did not predict worse biochemical outcomes at 5 years, said Dr. Christopher A. Peters of Mount Sinai School of Medicine, New York, at the annual meeting of the American Society for Therapeutic Radiation and Oncology.

High-risk men with a positive family history had significantly better biochemical control (94% vs. 80% of men with no family history). In intermediate-risk patients, there was a trend toward better control in those with a positive family history (100% vs. 93%). Low-risk patients with a family history of prostate cancer had an actuarial freedom-from-biochemical-failure rate (95%) similar to those without a family history.

Family history was not a significant predictor, however, when its impact was weighed with that of other factors in a multivariate analysis. The only significant factors affecting prostate-specific antigen (PSA) failure at 5 years were use of hormone therapy, a biologically effective radiation dose >150 Gy, initial PSA level, and Gleason score.

“You can confidently say to the patient, 'You would not do any worse [because] you have your family history,'” Dr. Peters said in an interview.

He and his coauthors identified 2,652 consecutive patients with clinically localized prostate cancer who were treated with low-dose-rate brachytherapy alone or in combination with external beam radiotherapy or hormone ablation from 1992 to 2005. They found family history information for 1,738 of these patients, among whom 187 men (11%) had a first-degree relative with prostate cancer. The minimum follow-up for inclusion in the study was 2 years; median follow-up was 5 years.

Patients with a family history of prostate cancer were younger (median 65 years), compared with those with no history (67 years). Those without a family history also had significantly fewer low-dose implants (2.7% vs. 10.8%). Both findings were statistically significant.

A patient with a family history of prostate cancer won't do any worse because of that history. DR. PETERS

LOS ANGELES — Dad had prostate cancer. So did a brother. Does this mean a worse prognosis for the patient?

To answer this, researchers compared rates of freedom from biochemical failure in a retrospective study of 1,738 men treated with low-dose-rate brachytherapy alone or combined with external beam radio- therapy or hormone ablation. A history of prostate cancer in one or more first-degree relatives did not predict worse biochemical outcomes at 5 years, said Dr. Christopher A. Peters of Mount Sinai School of Medicine, New York, at the annual meeting of the American Society for Therapeutic Radiation and Oncology.

High-risk men with a positive family history had significantly better biochemical control (94% vs. 80% of men with no family history). In intermediate-risk patients, there was a trend toward better control in those with a positive family history (100% vs. 93%). Low-risk patients with a family history of prostate cancer had an actuarial freedom-from-biochemical-failure rate (95%) similar to those without a family history.

Family history was not a significant predictor, however, when its impact was weighed with that of other factors in a multivariate analysis. The only significant factors affecting prostate-specific antigen (PSA) failure at 5 years were use of hormone therapy, a biologically effective radiation dose >150 Gy, initial PSA level, and Gleason score.

“You can confidently say to the patient, 'You would not do any worse [because] you have your family history,'” Dr. Peters said in an interview.

He and his coauthors identified 2,652 consecutive patients with clinically localized prostate cancer who were treated with low-dose-rate brachytherapy alone or in combination with external beam radiotherapy or hormone ablation from 1992 to 2005. They found family history information for 1,738 of these patients, among whom 187 men (11%) had a first-degree relative with prostate cancer. The minimum follow-up for inclusion in the study was 2 years; median follow-up was 5 years.

Patients with a family history of prostate cancer were younger (median 65 years), compared with those with no history (67 years). Those without a family history also had significantly fewer low-dose implants (2.7% vs. 10.8%). Both findings were statistically significant.

A patient with a family history of prostate cancer won't do any worse because of that history. DR. PETERS

LOS ANGELES — Dad had prostate cancer. So did a brother. Does this mean a worse prognosis for the patient?

To answer this, researchers compared rates of freedom from biochemical failure in a retrospective study of 1,738 men treated with low-dose-rate brachytherapy alone or combined with external beam radio- therapy or hormone ablation. A history of prostate cancer in one or more first-degree relatives did not predict worse biochemical outcomes at 5 years, said Dr. Christopher A. Peters of Mount Sinai School of Medicine, New York, at the annual meeting of the American Society for Therapeutic Radiation and Oncology.

High-risk men with a positive family history had significantly better biochemical control (94% vs. 80% of men with no family history). In intermediate-risk patients, there was a trend toward better control in those with a positive family history (100% vs. 93%). Low-risk patients with a family history of prostate cancer had an actuarial freedom-from-biochemical-failure rate (95%) similar to those without a family history.

Family history was not a significant predictor, however, when its impact was weighed with that of other factors in a multivariate analysis. The only significant factors affecting prostate-specific antigen (PSA) failure at 5 years were use of hormone therapy, a biologically effective radiation dose >150 Gy, initial PSA level, and Gleason score.

“You can confidently say to the patient, 'You would not do any worse [because] you have your family history,'” Dr. Peters said in an interview.

He and his coauthors identified 2,652 consecutive patients with clinically localized prostate cancer who were treated with low-dose-rate brachytherapy alone or in combination with external beam radiotherapy or hormone ablation from 1992 to 2005. They found family history information for 1,738 of these patients, among whom 187 men (11%) had a first-degree relative with prostate cancer. The minimum follow-up for inclusion in the study was 2 years; median follow-up was 5 years.

Patients with a family history of prostate cancer were younger (median 65 years), compared with those with no history (67 years). Those without a family history also had significantly fewer low-dose implants (2.7% vs. 10.8%). Both findings were statistically significant.

A patient with a family history of prostate cancer won't do any worse because of that history. DR. PETERS

A population-based review of more than 9,000 older men diagnosed with early-stage prostate cancer supports the controversial strategy of not treating less aggressive disease in the elderly.

Although most of the cancers went untreated, 10 years after diagnosis only 3%–7% of men with low- or moderate-grade disease had died of prostate cancer. Not surprisingly, mortality was higher, 23%, in men with high-grade disease.

“For elderly men, the survival benefit of treatment is most likely modest. The majority of patients died of other complaints or were still alive,” Grace Lu-Yao, Ph.D., lead investigator, said during a press Webcast in advance of a symposium on genitourinary cancers that was sponsored by the American Society for Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

Investigators used Medicare claims linked to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify 9,018 men diagnosed with stage I or II prostate cancer between 1992 and 2002. None had local therapy (surgery or radiation) or hormonal therapy in the 6 months after diagnosis, said Dr. Lu-Yao, an epidemiologist at the Cancer Institute of New Jersey, New Brunswick.

Although 2,675 men received treatment subsequently, long periods without therapy were common. Investigators reported the median interval between diagnosis and start of cancer therapy to be 10.6 years (127 months). About two-thirds of the population was categorized as either dying of other causes or not experiencing a cancer progression for which they were treated with surgery or radiation.

Compared with previous studies reporting higher mortality rates, the new analysis has the advantage of looking at many more men, older men, and men diagnosed in the era of prostate-specific antigen (PSA) screening. Dr. Lu-Yao said more than 5,000 participants were older than 75 years in the study; the median age was 77 years. Nearly two-thirds of the population had T1 disease.

She noted many men were unlikely to have been diagnosed before PSA screening, which can detect prostate cancer 6–13 years before the slow-growing disease is diagnosed clinically.

A population-based review of more than 9,000 older men diagnosed with early-stage prostate cancer supports the controversial strategy of not treating less aggressive disease in the elderly.

Although most of the cancers went untreated, 10 years after diagnosis only 3%–7% of men with low- or moderate-grade disease had died of prostate cancer. Not surprisingly, mortality was higher, 23%, in men with high-grade disease.

“For elderly men, the survival benefit of treatment is most likely modest. The majority of patients died of other complaints or were still alive,” Grace Lu-Yao, Ph.D., lead investigator, said during a press Webcast in advance of a symposium on genitourinary cancers that was sponsored by the American Society for Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

Investigators used Medicare claims linked to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify 9,018 men diagnosed with stage I or II prostate cancer between 1992 and 2002. None had local therapy (surgery or radiation) or hormonal therapy in the 6 months after diagnosis, said Dr. Lu-Yao, an epidemiologist at the Cancer Institute of New Jersey, New Brunswick.

Although 2,675 men received treatment subsequently, long periods without therapy were common. Investigators reported the median interval between diagnosis and start of cancer therapy to be 10.6 years (127 months). About two-thirds of the population was categorized as either dying of other causes or not experiencing a cancer progression for which they were treated with surgery or radiation.

Compared with previous studies reporting higher mortality rates, the new analysis has the advantage of looking at many more men, older men, and men diagnosed in the era of prostate-specific antigen (PSA) screening. Dr. Lu-Yao said more than 5,000 participants were older than 75 years in the study; the median age was 77 years. Nearly two-thirds of the population had T1 disease.

She noted many men were unlikely to have been diagnosed before PSA screening, which can detect prostate cancer 6–13 years before the slow-growing disease is diagnosed clinically.

A population-based review of more than 9,000 older men diagnosed with early-stage prostate cancer supports the controversial strategy of not treating less aggressive disease in the elderly.

Although most of the cancers went untreated, 10 years after diagnosis only 3%–7% of men with low- or moderate-grade disease had died of prostate cancer. Not surprisingly, mortality was higher, 23%, in men with high-grade disease.

“For elderly men, the survival benefit of treatment is most likely modest. The majority of patients died of other complaints or were still alive,” Grace Lu-Yao, Ph.D., lead investigator, said during a press Webcast in advance of a symposium on genitourinary cancers that was sponsored by the American Society for Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

Investigators used Medicare claims linked to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify 9,018 men diagnosed with stage I or II prostate cancer between 1992 and 2002. None had local therapy (surgery or radiation) or hormonal therapy in the 6 months after diagnosis, said Dr. Lu-Yao, an epidemiologist at the Cancer Institute of New Jersey, New Brunswick.

Although 2,675 men received treatment subsequently, long periods without therapy were common. Investigators reported the median interval between diagnosis and start of cancer therapy to be 10.6 years (127 months). About two-thirds of the population was categorized as either dying of other causes or not experiencing a cancer progression for which they were treated with surgery or radiation.

Compared with previous studies reporting higher mortality rates, the new analysis has the advantage of looking at many more men, older men, and men diagnosed in the era of prostate-specific antigen (PSA) screening. Dr. Lu-Yao said more than 5,000 participants were older than 75 years in the study; the median age was 77 years. Nearly two-thirds of the population had T1 disease.

She noted many men were unlikely to have been diagnosed before PSA screening, which can detect prostate cancer 6–13 years before the slow-growing disease is diagnosed clinically.

ATLANTA — Noncompliance is the main cause of aspirin resistance, according to investigators who studied aspirin response in 230 people, most of whom had a history of myocardial infarction.

The study initially classified up to 30% of the participants as aspirin resistant, but in the end, only 4% of 185 people in whom aspirin response was measured met a conservative definition of aspirin resistance. These seven patients were determined to have a low response to aspirin. One person violated the study's protocols by taking a nonaspirin nonsteroidal anti-inflammatory drug (NANSAID) that would have interfered with aspirin's effects.

Among participants who complied with the protocol, aspirin responses were normally distributed, Dr. Kenneth A. Schwartz reported at the annual meeting of the American Society of Hematology. No difference was seen between those with a history of MI and those in a control group.

“In my way of thinking, there are no people other than NANSAID people that you can label as truly aspirin resistant based on genetics or some other prior inability to respond to aspirin,” Dr. Schwartz, professor of medicine, Michigan State University, East Lansing, said in an interview alongside his poster.

Physicians should focus on compliance rather than resistance, he said, recommending that they test patients for aspirin use when they appear to be resistant. “In our studies, we found about 30% of patients could be labeled as aspirin resistant, and 90% of them [62 of 69 patients] were noncompliant,” he said.

Dr. Schwartz and his colleagues started with 230 evaluable individuals, all of whom were told not to take aspirin for 7 days. After the 7 days, they removed 45 from the study because they were not compliant with the protocol during the withdrawal period.

This left 185 participants—146 with a history of MI and 39 normal controls—in whom aspirin response was measured with platelet prostaglandin agonist (PPA) stimulated light aggregometry. The participants' average age was 61 years, and 63% were men. Blood was drawn twice: immediately after the 7-day washout period, and then 2 hours after a nurse observed each participant ingesting 365 mg of aspirin.

“These patients were very special because we were sure they were off aspirin because we checked with arachidonic acid,” Dr. Schwartz said. “And we were sure that they were on aspirin … because we watched them take the aspirin. And that's why we got a nice normal curve.”

Arachidonic acid testing can reveal whether a patient is taking aspirin, which inhibits cyclo-oxygenase-1-mediated events leading to platelet aggregation. A relatively new test, PPA-stimulated light aggregometry allowed the investigators to measure the extent of aspirin-induced platelet inhibition. To define net aspirin response, they subtracted the slope of each patient's post-aspirin PPA light aggregation curve from the curve recorded when the patient was aspirin free.

While the seven low responders had a decrease that was less than one standard deviation, the investigators suggested they might not be a distinct population but the bottom of a normal bell-shape distribution curve. “If there was a separate group of patients that were aspirin resistant, this would show a subgroup in which there was a poor response, and we don't see that,” he said.

In an earlier phase of the study, he said, arachidonic acid failed to show the expected aspirin inhibition in 17 of 192 heart attack patients who had been prescribed aspirin. All but one showed aspirin inhibition when they were retested 2 hours after being observed taking aspirin, however.

The 1 patient admitted to taking a NANSAID in violation of the protocol, leaving the investigators to conclude that the other 16 were not aspirin resistant but rather were noncompliant with their prescribed aspirin use.

Dr. Schwartz said he did not know why patients were not compliant but that they should be counseled about the importance of aspirin to their survival. “If you don't get your aspirin, you don't get your benefit,” he said. “Aspirin is one of the most effective drugs we have in terms of platelet inhibition.” n

'We found about 30% of patients could be labeled as aspirin resistant, and 90% of them were noncompliant.' DR. SCHWARTZ

ATLANTA — Noncompliance is the main cause of aspirin resistance, according to investigators who studied aspirin response in 230 people, most of whom had a history of myocardial infarction.

The study initially classified up to 30% of the participants as aspirin resistant, but in the end, only 4% of 185 people in whom aspirin response was measured met a conservative definition of aspirin resistance. These seven patients were determined to have a low response to aspirin. One person violated the study's protocols by taking a nonaspirin nonsteroidal anti-inflammatory drug (NANSAID) that would have interfered with aspirin's effects.

Among participants who complied with the protocol, aspirin responses were normally distributed, Dr. Kenneth A. Schwartz reported at the annual meeting of the American Society of Hematology. No difference was seen between those with a history of MI and those in a control group.

“In my way of thinking, there are no people other than NANSAID people that you can label as truly aspirin resistant based on genetics or some other prior inability to respond to aspirin,” Dr. Schwartz, professor of medicine, Michigan State University, East Lansing, said in an interview alongside his poster.

Physicians should focus on compliance rather than resistance, he said, recommending that they test patients for aspirin use when they appear to be resistant. “In our studies, we found about 30% of patients could be labeled as aspirin resistant, and 90% of them [62 of 69 patients] were noncompliant,” he said.

Dr. Schwartz and his colleagues started with 230 evaluable individuals, all of whom were told not to take aspirin for 7 days. After the 7 days, they removed 45 from the study because they were not compliant with the protocol during the withdrawal period.

This left 185 participants—146 with a history of MI and 39 normal controls—in whom aspirin response was measured with platelet prostaglandin agonist (PPA) stimulated light aggregometry. The participants' average age was 61 years, and 63% were men. Blood was drawn twice: immediately after the 7-day washout period, and then 2 hours after a nurse observed each participant ingesting 365 mg of aspirin.

“These patients were very special because we were sure they were off aspirin because we checked with arachidonic acid,” Dr. Schwartz said. “And we were sure that they were on aspirin … because we watched them take the aspirin. And that's why we got a nice normal curve.”

Arachidonic acid testing can reveal whether a patient is taking aspirin, which inhibits cyclo-oxygenase-1-mediated events leading to platelet aggregation. A relatively new test, PPA-stimulated light aggregometry allowed the investigators to measure the extent of aspirin-induced platelet inhibition. To define net aspirin response, they subtracted the slope of each patient's post-aspirin PPA light aggregation curve from the curve recorded when the patient was aspirin free.

While the seven low responders had a decrease that was less than one standard deviation, the investigators suggested they might not be a distinct population but the bottom of a normal bell-shape distribution curve. “If there was a separate group of patients that were aspirin resistant, this would show a subgroup in which there was a poor response, and we don't see that,” he said.

In an earlier phase of the study, he said, arachidonic acid failed to show the expected aspirin inhibition in 17 of 192 heart attack patients who had been prescribed aspirin. All but one showed aspirin inhibition when they were retested 2 hours after being observed taking aspirin, however.

The 1 patient admitted to taking a NANSAID in violation of the protocol, leaving the investigators to conclude that the other 16 were not aspirin resistant but rather were noncompliant with their prescribed aspirin use.

Dr. Schwartz said he did not know why patients were not compliant but that they should be counseled about the importance of aspirin to their survival. “If you don't get your aspirin, you don't get your benefit,” he said. “Aspirin is one of the most effective drugs we have in terms of platelet inhibition.” n

'We found about 30% of patients could be labeled as aspirin resistant, and 90% of them were noncompliant.' DR. SCHWARTZ

ATLANTA — Noncompliance is the main cause of aspirin resistance, according to investigators who studied aspirin response in 230 people, most of whom had a history of myocardial infarction.

The study initially classified up to 30% of the participants as aspirin resistant, but in the end, only 4% of 185 people in whom aspirin response was measured met a conservative definition of aspirin resistance. These seven patients were determined to have a low response to aspirin. One person violated the study's protocols by taking a nonaspirin nonsteroidal anti-inflammatory drug (NANSAID) that would have interfered with aspirin's effects.

Among participants who complied with the protocol, aspirin responses were normally distributed, Dr. Kenneth A. Schwartz reported at the annual meeting of the American Society of Hematology. No difference was seen between those with a history of MI and those in a control group.

“In my way of thinking, there are no people other than NANSAID people that you can label as truly aspirin resistant based on genetics or some other prior inability to respond to aspirin,” Dr. Schwartz, professor of medicine, Michigan State University, East Lansing, said in an interview alongside his poster.

Physicians should focus on compliance rather than resistance, he said, recommending that they test patients for aspirin use when they appear to be resistant. “In our studies, we found about 30% of patients could be labeled as aspirin resistant, and 90% of them [62 of 69 patients] were noncompliant,” he said.

Dr. Schwartz and his colleagues started with 230 evaluable individuals, all of whom were told not to take aspirin for 7 days. After the 7 days, they removed 45 from the study because they were not compliant with the protocol during the withdrawal period.

This left 185 participants—146 with a history of MI and 39 normal controls—in whom aspirin response was measured with platelet prostaglandin agonist (PPA) stimulated light aggregometry. The participants' average age was 61 years, and 63% were men. Blood was drawn twice: immediately after the 7-day washout period, and then 2 hours after a nurse observed each participant ingesting 365 mg of aspirin.

“These patients were very special because we were sure they were off aspirin because we checked with arachidonic acid,” Dr. Schwartz said. “And we were sure that they were on aspirin … because we watched them take the aspirin. And that's why we got a nice normal curve.”

Arachidonic acid testing can reveal whether a patient is taking aspirin, which inhibits cyclo-oxygenase-1-mediated events leading to platelet aggregation. A relatively new test, PPA-stimulated light aggregometry allowed the investigators to measure the extent of aspirin-induced platelet inhibition. To define net aspirin response, they subtracted the slope of each patient's post-aspirin PPA light aggregation curve from the curve recorded when the patient was aspirin free.

While the seven low responders had a decrease that was less than one standard deviation, the investigators suggested they might not be a distinct population but the bottom of a normal bell-shape distribution curve. “If there was a separate group of patients that were aspirin resistant, this would show a subgroup in which there was a poor response, and we don't see that,” he said.

In an earlier phase of the study, he said, arachidonic acid failed to show the expected aspirin inhibition in 17 of 192 heart attack patients who had been prescribed aspirin. All but one showed aspirin inhibition when they were retested 2 hours after being observed taking aspirin, however.

The 1 patient admitted to taking a NANSAID in violation of the protocol, leaving the investigators to conclude that the other 16 were not aspirin resistant but rather were noncompliant with their prescribed aspirin use.

Dr. Schwartz said he did not know why patients were not compliant but that they should be counseled about the importance of aspirin to their survival. “If you don't get your aspirin, you don't get your benefit,” he said. “Aspirin is one of the most effective drugs we have in terms of platelet inhibition.” n

'We found about 30% of patients could be labeled as aspirin resistant, and 90% of them were noncompliant.' DR. SCHWARTZ