Sharon Worcester

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women taking bisphosphonates, even among those treated for up to 10 years, a secondary analysis of data from three large randomized bisphosphonate trials suggests.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users. However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California at San Francisco and his colleagues wrote.

The data analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT); the relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in FIT, 1.50 for zoledronic acid vs. placebo in HORIZON-PFT, and 1.33 for continued alendronate use vs. placebo in the FLEX trial, the investigators reported (N. Engl. J. Med. 2010 March 24 [doi10.1056/NEJMoa1001086

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years and those who discontinued treatment, they wrote.

Since radiographs in those with fractures were generally not available, atypical features could not be assessed; if this information were available, it is likely the femoral fracture rate would be even lower, they said.

The findings support those from population-based studies, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but which attributed that to increased use of alendronate in high-risk patients rather than to use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, including 71 vertebral fractures and 29 nonvertebral fractures—including 11 hip fractures. Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures seen in the three trials, “the hypothetical risk is quite small,” they concluded

Additional research is needed to more fully address bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

While the current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women taking bisphosphonates, even among those treated for up to 10 years, a secondary analysis of data from three large randomized bisphosphonate trials suggests.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users. However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California at San Francisco and his colleagues wrote.

The data analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT); the relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in FIT, 1.50 for zoledronic acid vs. placebo in HORIZON-PFT, and 1.33 for continued alendronate use vs. placebo in the FLEX trial, the investigators reported (N. Engl. J. Med. 2010 March 24 [doi10.1056/NEJMoa1001086

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years and those who discontinued treatment, they wrote.

Since radiographs in those with fractures were generally not available, atypical features could not be assessed; if this information were available, it is likely the femoral fracture rate would be even lower, they said.

The findings support those from population-based studies, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but which attributed that to increased use of alendronate in high-risk patients rather than to use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, including 71 vertebral fractures and 29 nonvertebral fractures—including 11 hip fractures. Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures seen in the three trials, “the hypothetical risk is quite small,” they concluded

Additional research is needed to more fully address bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

While the current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women taking bisphosphonates, even among those treated for up to 10 years, a secondary analysis of data from three large randomized bisphosphonate trials suggests.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users. However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California at San Francisco and his colleagues wrote.

The data analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT); the relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in FIT, 1.50 for zoledronic acid vs. placebo in HORIZON-PFT, and 1.33 for continued alendronate use vs. placebo in the FLEX trial, the investigators reported (N. Engl. J. Med. 2010 March 24 [doi10.1056/NEJMoa1001086

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years and those who discontinued treatment, they wrote.

Since radiographs in those with fractures were generally not available, atypical features could not be assessed; if this information were available, it is likely the femoral fracture rate would be even lower, they said.

The findings support those from population-based studies, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but which attributed that to increased use of alendronate in high-risk patients rather than to use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, including 71 vertebral fractures and 29 nonvertebral fractures—including 11 hip fractures. Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures seen in the three trials, “the hypothetical risk is quite small,” they concluded

Additional research is needed to more fully address bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

While the current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women taking bisphosphonates, even among those treated for up to 10 years, a secondary analysis of data from three large randomized bisphosphonate trials suggests.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users. However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California at San Francisco and his colleagues wrote.

The data analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT); the relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in the FIT trial, 1.50 for zoledronic acid vs. placebo in the HORIZON-PFT trial, and 1.33 for continued alendronate use vs. placebo in the FLEX trial, the investigators reported (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMoa1001086]).

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years, they wrote.

Since radiographs in those with fractures were generally not available, atypical features—such as those associated with cortical thickness and fracture morphology—could not be assessed; if this information were available, it is likely the femoral fracture rate would be even lower, they said.

The findings support those from population base studied, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but which attributed that to the increased use of alendronate in high-risk patients rather than to the use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, including 71 vertebral fractures and 29 nonvertebral fractures, including 11 hip fractures. Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures seen in the three trials, “the hypothetical risk is quite small,” they concluded.

Additional research is needed to more fully address the matter of bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

While the current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064]).

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women taking bisphosphonates, even among those treated for up to 10 years, a secondary analysis of data from three large randomized bisphosphonate trials suggests.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users. However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California at San Francisco and his colleagues wrote.

The data analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT); the relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in the FIT trial, 1.50 for zoledronic acid vs. placebo in the HORIZON-PFT trial, and 1.33 for continued alendronate use vs. placebo in the FLEX trial, the investigators reported (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMoa1001086]).

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years, they wrote.

Since radiographs in those with fractures were generally not available, atypical features—such as those associated with cortical thickness and fracture morphology—could not be assessed; if this information were available, it is likely the femoral fracture rate would be even lower, they said.

The findings support those from population base studied, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but which attributed that to the increased use of alendronate in high-risk patients rather than to the use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, including 71 vertebral fractures and 29 nonvertebral fractures, including 11 hip fractures. Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures seen in the three trials, “the hypothetical risk is quite small,” they concluded.

Additional research is needed to more fully address the matter of bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

While the current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064]).

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women taking bisphosphonates, even among those treated for up to 10 years, a secondary analysis of data from three large randomized bisphosphonate trials suggests.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users. However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California at San Francisco and his colleagues wrote.

The data analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT); the relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in the FIT trial, 1.50 for zoledronic acid vs. placebo in the HORIZON-PFT trial, and 1.33 for continued alendronate use vs. placebo in the FLEX trial, the investigators reported (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMoa1001086]).

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years, they wrote.

Since radiographs in those with fractures were generally not available, atypical features—such as those associated with cortical thickness and fracture morphology—could not be assessed; if this information were available, it is likely the femoral fracture rate would be even lower, they said.

The findings support those from population base studied, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but which attributed that to the increased use of alendronate in high-risk patients rather than to the use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, including 71 vertebral fractures and 29 nonvertebral fractures, including 11 hip fractures. Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures seen in the three trials, “the hypothetical risk is quite small,” they concluded.

Additional research is needed to more fully address the matter of bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

While the current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064]).

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

MIAMI – Obstetricians may be lacking adequate information on the proper management of pregnancies affected by epidermolysis bullosa, findings from a survey suggested.

Of 195 Australian obstetricians who responded to the survey, 111 (57%) said information on epidermolysis bullosa (EB) is needed in prenatal clinics, Dr. Lizbeth Intong reported at the annual meeting of the American Academy of Dermatology.

Of the 195 (7%) respondents, 14 had encountered a pregnancy affected by EB; only 6 (43%) of the 14 said they conducted a literature search for information on the disease to help in their patient management, and only 4 (29%) comanaged their EB patients with a dermatologist, said Dr. Intong, a dermatologist at St. George Hospital in Sydney.

Mothers who had given birth to babies with EB, and mothers with EB who had given birth were also surveyed as part of the study. A total of 58 mothers who had babies with EB responded, and they had a total of 130 babies, including 67 (52%) born with EB.

Most babies were born by normal vaginal delivery, with a 5:1 ratio of normal vaginal deliveries to cesarean sections; the more severe the EB type, the more blistering was seen at birth.

Forty-one mothers with EB also responded to the survey. These mothers gave birth to a total of 104 babies, including 50 (48%) born with EB, mostly by normal vaginal delivery. In this group there was a 4:1 ratio of normal vaginal deliveries to C-sections.

Two of the mothers with EB reported that their condition worsened during pregnancy, and two said it improved; EB-related problems that were reported included blistering at the site of the adhesive tape used during an epidural and nipple blistering during breastfeeding, which led to a switch from breastfeeding to bottle feeding “There is an obvious need for information about EB in [prenatal] clinics,” Dr. Intong said, adding that based on the survey results, she now advises that normal vaginal delivery (no forceps or vacuum assistance) is generally safe, that C-section should be considered in severe cases to reduce birth trauma, that nonadhesive tapes and dressings be used on mothers with EB, and that mothers with EB receive counseling about proper care during breastfeeding, such as the use of nipple shields to help prevent blistering.

Dr. Intong said she had no conflicts of interest to disclose.

MIAMI – Obstetricians may be lacking adequate information on the proper management of pregnancies affected by epidermolysis bullosa, findings from a survey suggested.

Of 195 Australian obstetricians who responded to the survey, 111 (57%) said information on epidermolysis bullosa (EB) is needed in prenatal clinics, Dr. Lizbeth Intong reported at the annual meeting of the American Academy of Dermatology.

Of the 195 (7%) respondents, 14 had encountered a pregnancy affected by EB; only 6 (43%) of the 14 said they conducted a literature search for information on the disease to help in their patient management, and only 4 (29%) comanaged their EB patients with a dermatologist, said Dr. Intong, a dermatologist at St. George Hospital in Sydney.

Mothers who had given birth to babies with EB, and mothers with EB who had given birth were also surveyed as part of the study. A total of 58 mothers who had babies with EB responded, and they had a total of 130 babies, including 67 (52%) born with EB.

Most babies were born by normal vaginal delivery, with a 5:1 ratio of normal vaginal deliveries to cesarean sections; the more severe the EB type, the more blistering was seen at birth.

Forty-one mothers with EB also responded to the survey. These mothers gave birth to a total of 104 babies, including 50 (48%) born with EB, mostly by normal vaginal delivery. In this group there was a 4:1 ratio of normal vaginal deliveries to C-sections.

Two of the mothers with EB reported that their condition worsened during pregnancy, and two said it improved; EB-related problems that were reported included blistering at the site of the adhesive tape used during an epidural and nipple blistering during breastfeeding, which led to a switch from breastfeeding to bottle feeding “There is an obvious need for information about EB in [prenatal] clinics,” Dr. Intong said, adding that based on the survey results, she now advises that normal vaginal delivery (no forceps or vacuum assistance) is generally safe, that C-section should be considered in severe cases to reduce birth trauma, that nonadhesive tapes and dressings be used on mothers with EB, and that mothers with EB receive counseling about proper care during breastfeeding, such as the use of nipple shields to help prevent blistering.

Dr. Intong said she had no conflicts of interest to disclose.

MIAMI – Obstetricians may be lacking adequate information on the proper management of pregnancies affected by epidermolysis bullosa, findings from a survey suggested.

Of 195 Australian obstetricians who responded to the survey, 111 (57%) said information on epidermolysis bullosa (EB) is needed in prenatal clinics, Dr. Lizbeth Intong reported at the annual meeting of the American Academy of Dermatology.

Of the 195 (7%) respondents, 14 had encountered a pregnancy affected by EB; only 6 (43%) of the 14 said they conducted a literature search for information on the disease to help in their patient management, and only 4 (29%) comanaged their EB patients with a dermatologist, said Dr. Intong, a dermatologist at St. George Hospital in Sydney.

Mothers who had given birth to babies with EB, and mothers with EB who had given birth were also surveyed as part of the study. A total of 58 mothers who had babies with EB responded, and they had a total of 130 babies, including 67 (52%) born with EB.

Most babies were born by normal vaginal delivery, with a 5:1 ratio of normal vaginal deliveries to cesarean sections; the more severe the EB type, the more blistering was seen at birth.

Forty-one mothers with EB also responded to the survey. These mothers gave birth to a total of 104 babies, including 50 (48%) born with EB, mostly by normal vaginal delivery. In this group there was a 4:1 ratio of normal vaginal deliveries to C-sections.

Two of the mothers with EB reported that their condition worsened during pregnancy, and two said it improved; EB-related problems that were reported included blistering at the site of the adhesive tape used during an epidural and nipple blistering during breastfeeding, which led to a switch from breastfeeding to bottle feeding “There is an obvious need for information about EB in [prenatal] clinics,” Dr. Intong said, adding that based on the survey results, she now advises that normal vaginal delivery (no forceps or vacuum assistance) is generally safe, that C-section should be considered in severe cases to reduce birth trauma, that nonadhesive tapes and dressings be used on mothers with EB, and that mothers with EB receive counseling about proper care during breastfeeding, such as the use of nipple shields to help prevent blistering.

Dr. Intong said she had no conflicts of interest to disclose.

MIAMI – The decision to perform sentinel lymph node biopsy in cutaneous melanomas with a Breslow depth of less than 1.0 mm should be based on histopathologic factors, findings from a series of 472 patients suggest.

Sentinel lymph node biopsy (SLNB) is important for staging and determining prognosis in thicker melanomas, but its role in thinner melanomas is more controversial. There is no clear consensus in the literature regarding which prognostic factors predict sentinel lymph node metastases in thin melanomas, Dr. Suzanne Berkman and her colleagues at the Washington (D.C.) Cancer Institute reported in a poster at the annual meeting of the American Academy of Dermatology.

In their series of patients who underwent SLNB between 1997 and 2008 at the institute, the investigators found Breslow depth, Clark level, and nodular subtype to be positively associated with SLNB positivity. Ulceration status was also associated with SLNB positivity, but this association did not reach statistical significance.

The mean Breslow depth of the melanomas in the study’s 472 patients was 2.11 mm. In all, 330 patients had a Breslow depth greater than 1.0 mm, and 142 had a Breslow depth of 1.0 mm or less (thin melanomas).

The American Joint Committee on Cancer recommends performing SLNB only on melanomas with a Breslow depth of 1.0 mm or greater with clinically uninvolved lymph nodes. The recommendation for thin melanomas is that SLNB be performed in those measuring less than 1.0 mm if there is ulceration and at least 1 mitosis per mm2 – particularly if Breslow depth is at least 0.75 mm.

The practice at the Washington Cancer Institute is to perform SLNB for all melanomas of a Breslow depth of at least 0.76 mm, and to biopsy those thinner than 0.76 mm that have adverse histopathologic factors, such as Clark level IV/V, ulceration, and high mitotic rate, the investigators reported. In their series, 55 patients with a mean Breslow depth of 3.26 mm had a positive SLNB.

Of the 330 patients with a Breslow depth greater than 1.0 mm, 16% had a positive SLNB, compared with only 2% of the 142 patients with thin melanomas. Mean Breslow depth in the patients in those groups with positive SLNB was 3.4 mm and 0.81 mm, respectively.

The rate of SLNB positivity in the study increased with increasing depth of invasion: In all, 2% of those with Breslow depth of 1.0 mm or less had a positive SLNB, compared with 10% of those with a depth of 1.01-2.0 mm, 23% of those with a depth of 2.01-4.00 mm, and 23% of those with a depth greater than 4.0 mm, the investigators noted.

Not only was positivity a function of Breslow depth, but Breslow depth correlated with disease progression and survival, as did SLNB positivity, the investigators found.

Local or distant recurrence occurred in 43 patients (9%) overall. Those with recurrence had a mean Breslow depth of 4.19 mm and a mean follow-up of 45 months. Only 17 of the 43 survived; they had a mean Breslow depth of 3.76 mm and a mean follow up of 58 months.

Of the 417 patients with a negative biopsy, 29 (7%) developed recurrence – including 1 with a thin melanoma – and 12 (3%) developed distant metastases. Of the 55 patients with a positive biopsy, 14 (25%) developed recurrence – including 1 with a thin melanoma – and 7 (13%) developed distant metastases. Death occurred in 4% of patients with a negative biopsy, compared with 16% of those with a positive biopsy.

“The results from our institution confirm the importance of SLNB on staging and prognosis in patients with cutaneous melanomas. We continue to perform SLNB in patients with thin melanomas and ulceration and high mitotic rate,” the investigators concluded.

The investigators reported no relevant disclosures related to the study.

MIAMI – The decision to perform sentinel lymph node biopsy in cutaneous melanomas with a Breslow depth of less than 1.0 mm should be based on histopathologic factors, findings from a series of 472 patients suggest.

Sentinel lymph node biopsy (SLNB) is important for staging and determining prognosis in thicker melanomas, but its role in thinner melanomas is more controversial. There is no clear consensus in the literature regarding which prognostic factors predict sentinel lymph node metastases in thin melanomas, Dr. Suzanne Berkman and her colleagues at the Washington (D.C.) Cancer Institute reported in a poster at the annual meeting of the American Academy of Dermatology.

In their series of patients who underwent SLNB between 1997 and 2008 at the institute, the investigators found Breslow depth, Clark level, and nodular subtype to be positively associated with SLNB positivity. Ulceration status was also associated with SLNB positivity, but this association did not reach statistical significance.

The mean Breslow depth of the melanomas in the study’s 472 patients was 2.11 mm. In all, 330 patients had a Breslow depth greater than 1.0 mm, and 142 had a Breslow depth of 1.0 mm or less (thin melanomas).

The American Joint Committee on Cancer recommends performing SLNB only on melanomas with a Breslow depth of 1.0 mm or greater with clinically uninvolved lymph nodes. The recommendation for thin melanomas is that SLNB be performed in those measuring less than 1.0 mm if there is ulceration and at least 1 mitosis per mm2 – particularly if Breslow depth is at least 0.75 mm.

The practice at the Washington Cancer Institute is to perform SLNB for all melanomas of a Breslow depth of at least 0.76 mm, and to biopsy those thinner than 0.76 mm that have adverse histopathologic factors, such as Clark level IV/V, ulceration, and high mitotic rate, the investigators reported. In their series, 55 patients with a mean Breslow depth of 3.26 mm had a positive SLNB.

Of the 330 patients with a Breslow depth greater than 1.0 mm, 16% had a positive SLNB, compared with only 2% of the 142 patients with thin melanomas. Mean Breslow depth in the patients in those groups with positive SLNB was 3.4 mm and 0.81 mm, respectively.

The rate of SLNB positivity in the study increased with increasing depth of invasion: In all, 2% of those with Breslow depth of 1.0 mm or less had a positive SLNB, compared with 10% of those with a depth of 1.01-2.0 mm, 23% of those with a depth of 2.01-4.00 mm, and 23% of those with a depth greater than 4.0 mm, the investigators noted.

Not only was positivity a function of Breslow depth, but Breslow depth correlated with disease progression and survival, as did SLNB positivity, the investigators found.

Local or distant recurrence occurred in 43 patients (9%) overall. Those with recurrence had a mean Breslow depth of 4.19 mm and a mean follow-up of 45 months. Only 17 of the 43 survived; they had a mean Breslow depth of 3.76 mm and a mean follow up of 58 months.

Of the 417 patients with a negative biopsy, 29 (7%) developed recurrence – including 1 with a thin melanoma – and 12 (3%) developed distant metastases. Of the 55 patients with a positive biopsy, 14 (25%) developed recurrence – including 1 with a thin melanoma – and 7 (13%) developed distant metastases. Death occurred in 4% of patients with a negative biopsy, compared with 16% of those with a positive biopsy.

“The results from our institution confirm the importance of SLNB on staging and prognosis in patients with cutaneous melanomas. We continue to perform SLNB in patients with thin melanomas and ulceration and high mitotic rate,” the investigators concluded.

The investigators reported no relevant disclosures related to the study.

MIAMI – The decision to perform sentinel lymph node biopsy in cutaneous melanomas with a Breslow depth of less than 1.0 mm should be based on histopathologic factors, findings from a series of 472 patients suggest.

Sentinel lymph node biopsy (SLNB) is important for staging and determining prognosis in thicker melanomas, but its role in thinner melanomas is more controversial. There is no clear consensus in the literature regarding which prognostic factors predict sentinel lymph node metastases in thin melanomas, Dr. Suzanne Berkman and her colleagues at the Washington (D.C.) Cancer Institute reported in a poster at the annual meeting of the American Academy of Dermatology.

In their series of patients who underwent SLNB between 1997 and 2008 at the institute, the investigators found Breslow depth, Clark level, and nodular subtype to be positively associated with SLNB positivity. Ulceration status was also associated with SLNB positivity, but this association did not reach statistical significance.

The mean Breslow depth of the melanomas in the study’s 472 patients was 2.11 mm. In all, 330 patients had a Breslow depth greater than 1.0 mm, and 142 had a Breslow depth of 1.0 mm or less (thin melanomas).

The American Joint Committee on Cancer recommends performing SLNB only on melanomas with a Breslow depth of 1.0 mm or greater with clinically uninvolved lymph nodes. The recommendation for thin melanomas is that SLNB be performed in those measuring less than 1.0 mm if there is ulceration and at least 1 mitosis per mm2 – particularly if Breslow depth is at least 0.75 mm.

The practice at the Washington Cancer Institute is to perform SLNB for all melanomas of a Breslow depth of at least 0.76 mm, and to biopsy those thinner than 0.76 mm that have adverse histopathologic factors, such as Clark level IV/V, ulceration, and high mitotic rate, the investigators reported. In their series, 55 patients with a mean Breslow depth of 3.26 mm had a positive SLNB.

Of the 330 patients with a Breslow depth greater than 1.0 mm, 16% had a positive SLNB, compared with only 2% of the 142 patients with thin melanomas. Mean Breslow depth in the patients in those groups with positive SLNB was 3.4 mm and 0.81 mm, respectively.

The rate of SLNB positivity in the study increased with increasing depth of invasion: In all, 2% of those with Breslow depth of 1.0 mm or less had a positive SLNB, compared with 10% of those with a depth of 1.01-2.0 mm, 23% of those with a depth of 2.01-4.00 mm, and 23% of those with a depth greater than 4.0 mm, the investigators noted.

Not only was positivity a function of Breslow depth, but Breslow depth correlated with disease progression and survival, as did SLNB positivity, the investigators found.

Local or distant recurrence occurred in 43 patients (9%) overall. Those with recurrence had a mean Breslow depth of 4.19 mm and a mean follow-up of 45 months. Only 17 of the 43 survived; they had a mean Breslow depth of 3.76 mm and a mean follow up of 58 months.

Of the 417 patients with a negative biopsy, 29 (7%) developed recurrence – including 1 with a thin melanoma – and 12 (3%) developed distant metastases. Of the 55 patients with a positive biopsy, 14 (25%) developed recurrence – including 1 with a thin melanoma – and 7 (13%) developed distant metastases. Death occurred in 4% of patients with a negative biopsy, compared with 16% of those with a positive biopsy.

“The results from our institution confirm the importance of SLNB on staging and prognosis in patients with cutaneous melanomas. We continue to perform SLNB in patients with thin melanomas and ulceration and high mitotic rate,” the investigators concluded.

The investigators reported no relevant disclosures related to the study.

MIAMI -- Three newly identified syndromes on the clinical research agenda at the National Institutes of Health should be on dermatologists' radar screens, said Dr. Heidi H. Kong.

One of those important "new" syndromes is combined immunodeficiency syndrome associated with mutations in the dedicator of cytokinesis 8 protein (DOCK8). Cutaneous infections and aggressive skin cancers are hallmarks of the syndrome, and both require careful monitoring to help patients control the manifestations of this novel variant of combined immunodeficiency, said Dr. Kong at the annual meeting of the American Academy of Dermatology.

The NIH research described 11 patients (from eight families) who had recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE that are common in some variants of combined immunodeficiency (N. Engl. J. Med. 2010;361:2046-55).

Longitudinal data showed that among the cutaneous manifestations of the disease were recurrent Staphylococcus aureus skin infections with otitis externa, recurrent and severe herpes simplex virus, herpes zoster infections, severe molluscum contagiosum, and human papillomavirus infections. Other findings included severe atopic dermatitis--sometimes including rashes present since birth--with anaphylaxis; extremely aggressive squamous cell carcinomas; and in one patient, T-cell lymphoma/leukemia. This severe cutaneous phenotype of combined immunodeficiency was linked with the DOCK8 mutations.

"Unfortunately, I don't have a lot of treatment recommendations to give for this," said Dr. Kong, a dermatologist and an assistant clinical investigator at the NIH's Center for Cancer Research. "The most important thing we can do for these patients is to monitor for their cutaneous infections and to tend to their skin cancers."

The NIH is currently considering bone marrow transplantation for treating this inherited immunodeficiency, she said.

Other new syndromes that Dr. Kong described were:

Dominant Monocytopenia-Mycobacterial Infection
NIH investigators recently identified and described a subset of patients with nontuberculosis mycobacterial infections who also have monocytopenia, she said.

Dominant monocytopenia-mycobacterial infections are a distinct clinical syndrome involving increased susceptibility to mycobacterial, viral, and fungal infections, as well as malignancy. This can be transmitted in an autosomal dominant pattern, and also occurs sporadically (Blood 2010;115:1519-29).

In 18 patients studied, common infections included HPV and histoplasmosis. Ten patients developed one or more malignancies, including nine myelodysplasia/leukemia, one vulvar carcinoma and metastatic melanoma, one cervical carcinoma, one Bowen's disease of the vulva, and one multiple Epstein-Barr virus leiomyosarcoma.

Patients also commonly develop multiple inflammatory nodules, which usually resolve spontaneously, said Dr. Kong.

Deficiency to the Interleukin-1 Receptor Antagonist
DIRA is a recently discovered subset of the autoinflammatory syndrome that is characterized by a constellation of serious and potentially fatal symptoms, including bone tissue swelling and bone pain and deformity. Inflammation of the periosteum and a rash involving small pustules or extensive pustulosis covering most of a patient's body also occur.

Symptoms typically begin between birth and 2 weeks of age.

Anakinra, a synthetic form of human IL-1Ra, is an extremely effective and well-tolerated treatment for DIRA, Dr. Kong said. Treatment can result in dramatic improvement in the skin within weeks; however, discontinuation leads to relapse within days. Remember this if you are called on to evaluate a newborn with this syndrome, she advised.

Disclosures: Dr. Kong said that she has no relevant conflicts of interest in regard to her presentation.

MIAMI -- Three newly identified syndromes on the clinical research agenda at the National Institutes of Health should be on dermatologists' radar screens, said Dr. Heidi H. Kong.

One of those important "new" syndromes is combined immunodeficiency syndrome associated with mutations in the dedicator of cytokinesis 8 protein (DOCK8). Cutaneous infections and aggressive skin cancers are hallmarks of the syndrome, and both require careful monitoring to help patients control the manifestations of this novel variant of combined immunodeficiency, said Dr. Kong at the annual meeting of the American Academy of Dermatology.

The NIH research described 11 patients (from eight families) who had recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE that are common in some variants of combined immunodeficiency (N. Engl. J. Med. 2010;361:2046-55).

Longitudinal data showed that among the cutaneous manifestations of the disease were recurrent Staphylococcus aureus skin infections with otitis externa, recurrent and severe herpes simplex virus, herpes zoster infections, severe molluscum contagiosum, and human papillomavirus infections. Other findings included severe atopic dermatitis--sometimes including rashes present since birth--with anaphylaxis; extremely aggressive squamous cell carcinomas; and in one patient, T-cell lymphoma/leukemia. This severe cutaneous phenotype of combined immunodeficiency was linked with the DOCK8 mutations.

"Unfortunately, I don't have a lot of treatment recommendations to give for this," said Dr. Kong, a dermatologist and an assistant clinical investigator at the NIH's Center for Cancer Research. "The most important thing we can do for these patients is to monitor for their cutaneous infections and to tend to their skin cancers."

The NIH is currently considering bone marrow transplantation for treating this inherited immunodeficiency, she said.

Other new syndromes that Dr. Kong described were:

Dominant Monocytopenia-Mycobacterial Infection
NIH investigators recently identified and described a subset of patients with nontuberculosis mycobacterial infections who also have monocytopenia, she said.

Dominant monocytopenia-mycobacterial infections are a distinct clinical syndrome involving increased susceptibility to mycobacterial, viral, and fungal infections, as well as malignancy. This can be transmitted in an autosomal dominant pattern, and also occurs sporadically (Blood 2010;115:1519-29).

In 18 patients studied, common infections included HPV and histoplasmosis. Ten patients developed one or more malignancies, including nine myelodysplasia/leukemia, one vulvar carcinoma and metastatic melanoma, one cervical carcinoma, one Bowen's disease of the vulva, and one multiple Epstein-Barr virus leiomyosarcoma.

Patients also commonly develop multiple inflammatory nodules, which usually resolve spontaneously, said Dr. Kong.

Deficiency to the Interleukin-1 Receptor Antagonist
DIRA is a recently discovered subset of the autoinflammatory syndrome that is characterized by a constellation of serious and potentially fatal symptoms, including bone tissue swelling and bone pain and deformity. Inflammation of the periosteum and a rash involving small pustules or extensive pustulosis covering most of a patient's body also occur.

Symptoms typically begin between birth and 2 weeks of age.

Anakinra, a synthetic form of human IL-1Ra, is an extremely effective and well-tolerated treatment for DIRA, Dr. Kong said. Treatment can result in dramatic improvement in the skin within weeks; however, discontinuation leads to relapse within days. Remember this if you are called on to evaluate a newborn with this syndrome, she advised.

Disclosures: Dr. Kong said that she has no relevant conflicts of interest in regard to her presentation.

MIAMI -- Three newly identified syndromes on the clinical research agenda at the National Institutes of Health should be on dermatologists' radar screens, said Dr. Heidi H. Kong.

One of those important "new" syndromes is combined immunodeficiency syndrome associated with mutations in the dedicator of cytokinesis 8 protein (DOCK8). Cutaneous infections and aggressive skin cancers are hallmarks of the syndrome, and both require careful monitoring to help patients control the manifestations of this novel variant of combined immunodeficiency, said Dr. Kong at the annual meeting of the American Academy of Dermatology.

The NIH research described 11 patients (from eight families) who had recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE that are common in some variants of combined immunodeficiency (N. Engl. J. Med. 2010;361:2046-55).

Longitudinal data showed that among the cutaneous manifestations of the disease were recurrent Staphylococcus aureus skin infections with otitis externa, recurrent and severe herpes simplex virus, herpes zoster infections, severe molluscum contagiosum, and human papillomavirus infections. Other findings included severe atopic dermatitis--sometimes including rashes present since birth--with anaphylaxis; extremely aggressive squamous cell carcinomas; and in one patient, T-cell lymphoma/leukemia. This severe cutaneous phenotype of combined immunodeficiency was linked with the DOCK8 mutations.

"Unfortunately, I don't have a lot of treatment recommendations to give for this," said Dr. Kong, a dermatologist and an assistant clinical investigator at the NIH's Center for Cancer Research. "The most important thing we can do for these patients is to monitor for their cutaneous infections and to tend to their skin cancers."

The NIH is currently considering bone marrow transplantation for treating this inherited immunodeficiency, she said.

Other new syndromes that Dr. Kong described were:

Dominant Monocytopenia-Mycobacterial Infection
NIH investigators recently identified and described a subset of patients with nontuberculosis mycobacterial infections who also have monocytopenia, she said.

Dominant monocytopenia-mycobacterial infections are a distinct clinical syndrome involving increased susceptibility to mycobacterial, viral, and fungal infections, as well as malignancy. This can be transmitted in an autosomal dominant pattern, and also occurs sporadically (Blood 2010;115:1519-29).

In 18 patients studied, common infections included HPV and histoplasmosis. Ten patients developed one or more malignancies, including nine myelodysplasia/leukemia, one vulvar carcinoma and metastatic melanoma, one cervical carcinoma, one Bowen's disease of the vulva, and one multiple Epstein-Barr virus leiomyosarcoma.

Patients also commonly develop multiple inflammatory nodules, which usually resolve spontaneously, said Dr. Kong.

Deficiency to the Interleukin-1 Receptor Antagonist
DIRA is a recently discovered subset of the autoinflammatory syndrome that is characterized by a constellation of serious and potentially fatal symptoms, including bone tissue swelling and bone pain and deformity. Inflammation of the periosteum and a rash involving small pustules or extensive pustulosis covering most of a patient's body also occur.

Symptoms typically begin between birth and 2 weeks of age.

Anakinra, a synthetic form of human IL-1Ra, is an extremely effective and well-tolerated treatment for DIRA, Dr. Kong said. Treatment can result in dramatic improvement in the skin within weeks; however, discontinuation leads to relapse within days. Remember this if you are called on to evaluate a newborn with this syndrome, she advised.

Disclosures: Dr. Kong said that she has no relevant conflicts of interest in regard to her presentation.

Identifying myositis-specific and myositis-associated antibodies is important for determining subclasses of idiopathic inflammatory myopathies so that appropriate and timely therapy can be initiated, judging from findings from a retrospective study of 169 patients.

Researchers examined the sera from 130 patients who had been initially classified as having primary myositis, and from another 39 patients who had been classified as having overlap myositis (systemic sclerosis [13], rheumatoid arthritis [12], systemic lupus erythematosus [5] and Sj gren's syndrome [9]).

The initial classifications were made using original Bohan and Peter criteria, which are commonly used for classifying idiopathic inflammatory myopathy patients, but which don't take into consideration the presence of myositis-specific and myositis-associated antibodies.

Reevaluation of these patients based on the presence of myositis-specific and -associated antibodies led to 11 (8.5%) of the patients in the primary myositis group being reclassified as having overlap myositis. That classification means that the patients also fulfilled revised American College of Rheumatology criteria for systemic lupus erythematosus, rheumatic arthritis, systemic sclerosis, or Sj gren's syndrome, said Dr. Andrea V ncsa of the University of Debrecen Medical and Health Science Center (Hungary) and colleagues.

In addition to determining the prevalence of various myositis-specific and myositis-associated antibodies, the investigators also identified the clinical characteristics, disease course, and response to therapy associated with the antibodies. Myositis-specific antibodies included anti–Jo-1, –PL-7, –PL-12, –Mi-2, and –SRP. Myositis-associated antibodies included anti–SS-A, –SS-B, –U1snRNP, –Pm/Scl, and –Ku. The investigators characterized the patients into different clinicoserologic groups based on whether myositis-specific and myositis-associated antibodies were present, and further classified the patients as having polymyositis or dermatomyositis (Joint Bone Spine 2010 Feb. 24 [doi:10.1016/j.jbspin.2009.0.008]).

The researchers found that polymyositis was the most common myositis in overlap disease, occurring in 87% of patients in that group. Scleroderma was the most common overlapping disease, occurring in a third of patients in that group.

Antinuclear antibodies (ANA) were present in about 62% of overlap patients, compared with 25% of the primary myositis patients. ANA positivity was associated with an increased risk of associated connective tissue disease (odds ratio, 6.47), the investigators found.

Overall, nearly 40% of the myositis patients had autoantibodies, with anti–Jo-1 occurring most often and in similar frequency in both primary and overlap patients (in 18% and 19%, respectively). The presence of anti–Jo-1 was predominantly associated with polymyositis (in 84% of patients), vs. dermatomyositis, they noted.

Improving the classification of myositis patients using information about myositis-specific and -associated antibodies is important. Clinicians have to consider a variety of these overlap syndromes when treating myositis because the initial treatment provides the best chance of effectively controlling the disease and preventing long-term organ damage.

For example, the researchers found that interstitial lung disease, fever, arthritis, and mechanic's hand were all significantly positively associated with anti–Jo-1 autoantibody positivity in the patients in this study, and that anti–Jo-1 positivity was associated with a need for second-line treatment in primary myositis (OR, 1.95), but not in overlap disease (OR, 0.8).

Identifying myositis-specific and myositis-associated antibodies is important for determining subclasses of idiopathic inflammatory myopathies so that appropriate and timely therapy can be initiated, judging from findings from a retrospective study of 169 patients.

Researchers examined the sera from 130 patients who had been initially classified as having primary myositis, and from another 39 patients who had been classified as having overlap myositis (systemic sclerosis [13], rheumatoid arthritis [12], systemic lupus erythematosus [5] and Sj gren's syndrome [9]).

The initial classifications were made using original Bohan and Peter criteria, which are commonly used for classifying idiopathic inflammatory myopathy patients, but which don't take into consideration the presence of myositis-specific and myositis-associated antibodies.

Reevaluation of these patients based on the presence of myositis-specific and -associated antibodies led to 11 (8.5%) of the patients in the primary myositis group being reclassified as having overlap myositis. That classification means that the patients also fulfilled revised American College of Rheumatology criteria for systemic lupus erythematosus, rheumatic arthritis, systemic sclerosis, or Sj gren's syndrome, said Dr. Andrea V ncsa of the University of Debrecen Medical and Health Science Center (Hungary) and colleagues.

In addition to determining the prevalence of various myositis-specific and myositis-associated antibodies, the investigators also identified the clinical characteristics, disease course, and response to therapy associated with the antibodies. Myositis-specific antibodies included anti–Jo-1, –PL-7, –PL-12, –Mi-2, and –SRP. Myositis-associated antibodies included anti–SS-A, –SS-B, –U1snRNP, –Pm/Scl, and –Ku. The investigators characterized the patients into different clinicoserologic groups based on whether myositis-specific and myositis-associated antibodies were present, and further classified the patients as having polymyositis or dermatomyositis (Joint Bone Spine 2010 Feb. 24 [doi:10.1016/j.jbspin.2009.0.008]).

The researchers found that polymyositis was the most common myositis in overlap disease, occurring in 87% of patients in that group. Scleroderma was the most common overlapping disease, occurring in a third of patients in that group.

Antinuclear antibodies (ANA) were present in about 62% of overlap patients, compared with 25% of the primary myositis patients. ANA positivity was associated with an increased risk of associated connective tissue disease (odds ratio, 6.47), the investigators found.

Overall, nearly 40% of the myositis patients had autoantibodies, with anti–Jo-1 occurring most often and in similar frequency in both primary and overlap patients (in 18% and 19%, respectively). The presence of anti–Jo-1 was predominantly associated with polymyositis (in 84% of patients), vs. dermatomyositis, they noted.

Improving the classification of myositis patients using information about myositis-specific and -associated antibodies is important. Clinicians have to consider a variety of these overlap syndromes when treating myositis because the initial treatment provides the best chance of effectively controlling the disease and preventing long-term organ damage.

For example, the researchers found that interstitial lung disease, fever, arthritis, and mechanic's hand were all significantly positively associated with anti–Jo-1 autoantibody positivity in the patients in this study, and that anti–Jo-1 positivity was associated with a need for second-line treatment in primary myositis (OR, 1.95), but not in overlap disease (OR, 0.8).

Identifying myositis-specific and myositis-associated antibodies is important for determining subclasses of idiopathic inflammatory myopathies so that appropriate and timely therapy can be initiated, judging from findings from a retrospective study of 169 patients.

Researchers examined the sera from 130 patients who had been initially classified as having primary myositis, and from another 39 patients who had been classified as having overlap myositis (systemic sclerosis [13], rheumatoid arthritis [12], systemic lupus erythematosus [5] and Sj gren's syndrome [9]).

The initial classifications were made using original Bohan and Peter criteria, which are commonly used for classifying idiopathic inflammatory myopathy patients, but which don't take into consideration the presence of myositis-specific and myositis-associated antibodies.

Reevaluation of these patients based on the presence of myositis-specific and -associated antibodies led to 11 (8.5%) of the patients in the primary myositis group being reclassified as having overlap myositis. That classification means that the patients also fulfilled revised American College of Rheumatology criteria for systemic lupus erythematosus, rheumatic arthritis, systemic sclerosis, or Sj gren's syndrome, said Dr. Andrea V ncsa of the University of Debrecen Medical and Health Science Center (Hungary) and colleagues.

In addition to determining the prevalence of various myositis-specific and myositis-associated antibodies, the investigators also identified the clinical characteristics, disease course, and response to therapy associated with the antibodies. Myositis-specific antibodies included anti–Jo-1, –PL-7, –PL-12, –Mi-2, and –SRP. Myositis-associated antibodies included anti–SS-A, –SS-B, –U1snRNP, –Pm/Scl, and –Ku. The investigators characterized the patients into different clinicoserologic groups based on whether myositis-specific and myositis-associated antibodies were present, and further classified the patients as having polymyositis or dermatomyositis (Joint Bone Spine 2010 Feb. 24 [doi:10.1016/j.jbspin.2009.0.008]).

The researchers found that polymyositis was the most common myositis in overlap disease, occurring in 87% of patients in that group. Scleroderma was the most common overlapping disease, occurring in a third of patients in that group.

Antinuclear antibodies (ANA) were present in about 62% of overlap patients, compared with 25% of the primary myositis patients. ANA positivity was associated with an increased risk of associated connective tissue disease (odds ratio, 6.47), the investigators found.

Overall, nearly 40% of the myositis patients had autoantibodies, with anti–Jo-1 occurring most often and in similar frequency in both primary and overlap patients (in 18% and 19%, respectively). The presence of anti–Jo-1 was predominantly associated with polymyositis (in 84% of patients), vs. dermatomyositis, they noted.

Improving the classification of myositis patients using information about myositis-specific and -associated antibodies is important. Clinicians have to consider a variety of these overlap syndromes when treating myositis because the initial treatment provides the best chance of effectively controlling the disease and preventing long-term organ damage.

For example, the researchers found that interstitial lung disease, fever, arthritis, and mechanic's hand were all significantly positively associated with anti–Jo-1 autoantibody positivity in the patients in this study, and that anti–Jo-1 positivity was associated with a need for second-line treatment in primary myositis (OR, 1.95), but not in overlap disease (OR, 0.8).

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women who take bisphosphonates, even among those who are treated for up to 10 years, judging from findings from a secondary analysis of data from three large randomized bisphosphonate trials.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users.

However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up, showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California, San Francisco, and his colleagues wrote.

The data that were analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT).

The relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in FIT, 1.50 for zoledronic acid vs. placebo in HORIZON-PFT, and 1.33 for continued alendronate use vs. placebo in FLEX, the investigators reported (N. Engl. J. Med. 2010 March 24[doi: 10.1056/NEJMoa1001086

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years and those who discontinued treatment, they wrote.

Because radiographs in those with fractures were generally not available, atypical features—such as those associated with cortical thickness and fracture morphology—could not be assessed. If this information had been available, it is likely that the femoral fracture rate would be even lower, noted the investigators. The findings support those from population-based studies, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but that attributed that finding to the increased use of alendronate in high-risk patients rather than to the use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, comprising 71 vertebral fractures and 29 nonvertebral fractures (including 11 hip fractures).

Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures that were seen in the three trials, “the hypothetical risk is quite small,” they concluded

Additional research is needed to more fully address the matter of bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

The current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates.

That said, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck & Co. and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as from the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

X-ray shows an atypical fracture in a patient on bisphosphonates for years.

Source Courtesy Dr. Melvin Rosenwasser, Columbia University

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women who take bisphosphonates, even among those who are treated for up to 10 years, judging from findings from a secondary analysis of data from three large randomized bisphosphonate trials.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users.

However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up, showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California, San Francisco, and his colleagues wrote.

The data that were analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT).

The relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in FIT, 1.50 for zoledronic acid vs. placebo in HORIZON-PFT, and 1.33 for continued alendronate use vs. placebo in FLEX, the investigators reported (N. Engl. J. Med. 2010 March 24[doi: 10.1056/NEJMoa1001086

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years and those who discontinued treatment, they wrote.

Because radiographs in those with fractures were generally not available, atypical features—such as those associated with cortical thickness and fracture morphology—could not be assessed. If this information had been available, it is likely that the femoral fracture rate would be even lower, noted the investigators. The findings support those from population-based studies, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but that attributed that finding to the increased use of alendronate in high-risk patients rather than to the use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, comprising 71 vertebral fractures and 29 nonvertebral fractures (including 11 hip fractures).

Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures that were seen in the three trials, “the hypothetical risk is quite small,” they concluded

Additional research is needed to more fully address the matter of bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

The current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates.

That said, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck & Co. and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as from the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

X-ray shows an atypical fracture in a patient on bisphosphonates for years.

Source Courtesy Dr. Melvin Rosenwasser, Columbia University

The risk of subtrochanteric and diaphyseal femur fractures is not significantly increased in women who take bisphosphonates, even among those who are treated for up to 10 years, judging from findings from a secondary analysis of data from three large randomized bisphosphonate trials.

The findings follow several case reports that hinted at an increased risk of these atypical fractures in bisphosphonate users.

However, the current study, which included a review of 283 hip or femur fractures in 14,195 women with 51,287 patient-years of follow-up, showed that only 12 subtrochanteric or diaphyseal femur fractures occurred in 10 women, for a rate of 2.3 per 10,000 patient-years, Dennis M. Black, Ph.D., of the University of California, San Francisco, and his colleagues wrote.

The data that were analyzed in the current study were from the phase III Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT).

The relative hazard ratios for subtrochanteric and diaphyseal femur fractures were 1.03 for alendronate vs. placebo in FIT, 1.50 for zoledronic acid vs. placebo in HORIZON-PFT, and 1.33 for continued alendronate use vs. placebo in FLEX, the investigators reported (N. Engl. J. Med. 2010 March 24[doi: 10.1056/NEJMoa1001086

Even in the FLEX trial, which included up to 10 years of treatment with alendronate, the risk of femur fracture and atypical femur fracture was very low, with no significantly increased risk of fracture among those who continued treatment for the full 10 years and those who discontinued treatment, they wrote.

Because radiographs in those with fractures were generally not available, atypical features—such as those associated with cortical thickness and fracture morphology—could not be assessed. If this information had been available, it is likely that the femoral fracture rate would be even lower, noted the investigators. The findings support those from population-based studies, including one that found evidence of an increased incidence of hip and femur fractures with alendronate use, but that attributed that finding to the increased use of alendronate in high-risk patients rather than to the use of alendronate.

“Although we can confidently conclude that absolute rates of such fractures are low, wide confidence intervals (resulting from the very low incidence of events) preclude definitive conclusions regarding the relative risk of treatment,” the investigators wrote.

However, based on data they analyzed, the investigators estimated that 3 years of bisphosphonate treatment in 1,000 women with osteoporosis would prevent about 100 fractures, comprising 71 vertebral fractures and 29 nonvertebral fractures (including 11 hip fractures).

Balanced against the annual rate of 2.3 subtrochanteric and diaphyseal femur fractures that were seen in the three trials, “the hypothetical risk is quite small,” they concluded

Additional research is needed to more fully address the matter of bisphosphonate use and the risk of subtrochanteric and diaphyseal fractures, Dr. Elizabeth Shane wrote in an accompanying editorial.

The current findings provide assurance that these types of fractures are extremely rare, and that many more common and equally devastating hip fractures are prevented than are caused by bisphosphonates.

That said, physicians should “reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurement, and risk factors for fracture,” wrote Dr. Shane of Columbia University, New York (N. Engl. J. Med. 2010 March 24 [doi:10.1056/NEJMe1003064

It is reasonable to consider drug holidays, particularly in those with substantially reduced levels of bone turnover markers, but again, the evidence of persistent antifracture efficacy after discontinuation must be balanced with data showing that 10 vs. 5 years of alendronate use is associated with significantly fewer new vertebral and nonvertebral fractures in those with bone mineral density T scores of −2.5 or lower, she wrote.

Disclosures: This study was supported by Merck & Co. and Novartis. The investigators reported receiving grants, travel reimbursement, consulting fees, and lecture fees from Merck, Novartis, and several other pharmaceutical manufacturers, as well as from the National Osteoporosis Foundation. Dr. Shane reported receiving grants from Novartis, Merck, and other pharmaceutical manufacturers.

X-ray shows an atypical fracture in a patient on bisphosphonates for years.

Source Courtesy Dr. Melvin Rosenwasser, Columbia University

Major Finding: The overall rate of pediatric hospitalizations due to C. difficile infections increased from 7.24 to 12.80 per 10,000 hospitalizations, with the highest rates occurring in children aged 1–4 years (rate of 44.87/10,000), 5–9 years (35.27/10,000), and less than 1 year, except newborns (32.01/10,000).

Data Source: Data from 3,739 hospitals from the Health Care Cost and Utilization Project and the National Hospital Discharge Survey.

Disclosures: Dr. Zilberberg reported receiving grant support for this study from ViroPharma.

Pediatric hospitalizations associated with Clostridium difficile infections increased dramatically from 1997 through 2006, according to data from the Health Care Cost and Utilization Project and the National Hospital Discharge Survey.

The overall rate of such hospitalizations increased from 7.24 to 12.80 per 10,000 hospitalizations, with the highest rates occurring in children aged 1–4 years (rate of 44.87/10,000), 5–9 years (35.27/10,000), and less than 1 year, except newborns (32.01/10,000). The lowest rates were seen in newborns, defined as infants whose related hospitalizations originated at their birth (0.5/10,000), Dr. Marya D. Zilberberg of the University of Massachusetts, Amherst, and her colleagues reported.

Most of the increase in C. difficile infection (CDI)—related hospitalizations identified in this study occurred between 2000 and 2006, and this may reflect the spread of a new hypervirulent bacterial strain of C. difficile known as BI/NAP1/027. An increase in detection of the strain has coincided with reports of increasing CDI-related hospitalizations, the investigators noted (Emerg. Infect. Dis. 2010;16:604–9).

Evidence suggests that CDI is an increasingly prevalent diarrheal pathogen in children, and that a large proportion of pediatric CDI cases are community acquired. Many cases appear to be occurring without the exposure to antimicrobial drugs that has typically been a risk factor for CDI, they said, noting that the BI/NAP1/027 strain likely is related to these changes in pediatric CDI epidemiology; at least two reports show it has a prevalence of up to 38% in pediatric CDI populations, and it is associated with a fourfold increase in complication rates, compared with other strains.

To better characterize the epidemiology, the investigators performed a time-series analysis using information from the Kids' Inpatient Database (KID) of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project, which includes data from more than 3,700 hospitals in 38 states, and from the Centers for Disease Control and Prevention's National Hospital Discharge Survey, which includes information from about 500 noninstitutional, nonfederal, short-stay hospitals in the United States. The latter analysis allowed for cross-sectional characterization of all CDI hospitalizations, including separate analysis of newborn data not available from the KID.

In addition to the finding of an increasing rate of CDI-related hospitalizations in children, the investigators also found a similar increase in rotavirus-related hospitalizations.

Additional study is urgently needed to help better define the epidemiology of CDI, the investigators said, noting a particular need for more information about its role in the pathogenesis of disease in those under age 1 year who are not newborns. Laboratory testing for CDI is not routinely performed in those under age 1 year, because of their typically low rate of clinical disease and high rate of C. difficile carriage, and it remains unclear whether the relatively high rate of CDI-related hospitalizations in this group is a reflection of true disease or colonization, as a pathogenic role of C. difficile could not be definitively determined in this study, Dr. Zilberberg and her associates said.

Major Finding: The overall rate of pediatric hospitalizations due to C. difficile infections increased from 7.24 to 12.80 per 10,000 hospitalizations, with the highest rates occurring in children aged 1–4 years (rate of 44.87/10,000), 5–9 years (35.27/10,000), and less than 1 year, except newborns (32.01/10,000).

Data Source: Data from 3,739 hospitals from the Health Care Cost and Utilization Project and the National Hospital Discharge Survey.

Disclosures: Dr. Zilberberg reported receiving grant support for this study from ViroPharma.

Pediatric hospitalizations associated with Clostridium difficile infections increased dramatically from 1997 through 2006, according to data from the Health Care Cost and Utilization Project and the National Hospital Discharge Survey.

The overall rate of such hospitalizations increased from 7.24 to 12.80 per 10,000 hospitalizations, with the highest rates occurring in children aged 1–4 years (rate of 44.87/10,000), 5–9 years (35.27/10,000), and less than 1 year, except newborns (32.01/10,000). The lowest rates were seen in newborns, defined as infants whose related hospitalizations originated at their birth (0.5/10,000), Dr. Marya D. Zilberberg of the University of Massachusetts, Amherst, and her colleagues reported.

Most of the increase in C. difficile infection (CDI)—related hospitalizations identified in this study occurred between 2000 and 2006, and this may reflect the spread of a new hypervirulent bacterial strain of C. difficile known as BI/NAP1/027. An increase in detection of the strain has coincided with reports of increasing CDI-related hospitalizations, the investigators noted (Emerg. Infect. Dis. 2010;16:604–9).

Evidence suggests that CDI is an increasingly prevalent diarrheal pathogen in children, and that a large proportion of pediatric CDI cases are community acquired. Many cases appear to be occurring without the exposure to antimicrobial drugs that has typically been a risk factor for CDI, they said, noting that the BI/NAP1/027 strain likely is related to these changes in pediatric CDI epidemiology; at least two reports show it has a prevalence of up to 38% in pediatric CDI populations, and it is associated with a fourfold increase in complication rates, compared with other strains.

To better characterize the epidemiology, the investigators performed a time-series analysis using information from the Kids' Inpatient Database (KID) of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project, which includes data from more than 3,700 hospitals in 38 states, and from the Centers for Disease Control and Prevention's National Hospital Discharge Survey, which includes information from about 500 noninstitutional, nonfederal, short-stay hospitals in the United States. The latter analysis allowed for cross-sectional characterization of all CDI hospitalizations, including separate analysis of newborn data not available from the KID.

In addition to the finding of an increasing rate of CDI-related hospitalizations in children, the investigators also found a similar increase in rotavirus-related hospitalizations.

Additional study is urgently needed to help better define the epidemiology of CDI, the investigators said, noting a particular need for more information about its role in the pathogenesis of disease in those under age 1 year who are not newborns. Laboratory testing for CDI is not routinely performed in those under age 1 year, because of their typically low rate of clinical disease and high rate of C. difficile carriage, and it remains unclear whether the relatively high rate of CDI-related hospitalizations in this group is a reflection of true disease or colonization, as a pathogenic role of C. difficile could not be definitively determined in this study, Dr. Zilberberg and her associates said.

Major Finding: The overall rate of pediatric hospitalizations due to C. difficile infections increased from 7.24 to 12.80 per 10,000 hospitalizations, with the highest rates occurring in children aged 1–4 years (rate of 44.87/10,000), 5–9 years (35.27/10,000), and less than 1 year, except newborns (32.01/10,000).

Data Source: Data from 3,739 hospitals from the Health Care Cost and Utilization Project and the National Hospital Discharge Survey.

Disclosures: Dr. Zilberberg reported receiving grant support for this study from ViroPharma.

Pediatric hospitalizations associated with Clostridium difficile infections increased dramatically from 1997 through 2006, according to data from the Health Care Cost and Utilization Project and the National Hospital Discharge Survey.

The overall rate of such hospitalizations increased from 7.24 to 12.80 per 10,000 hospitalizations, with the highest rates occurring in children aged 1–4 years (rate of 44.87/10,000), 5–9 years (35.27/10,000), and less than 1 year, except newborns (32.01/10,000). The lowest rates were seen in newborns, defined as infants whose related hospitalizations originated at their birth (0.5/10,000), Dr. Marya D. Zilberberg of the University of Massachusetts, Amherst, and her colleagues reported.

Most of the increase in C. difficile infection (CDI)—related hospitalizations identified in this study occurred between 2000 and 2006, and this may reflect the spread of a new hypervirulent bacterial strain of C. difficile known as BI/NAP1/027. An increase in detection of the strain has coincided with reports of increasing CDI-related hospitalizations, the investigators noted (Emerg. Infect. Dis. 2010;16:604–9).

Evidence suggests that CDI is an increasingly prevalent diarrheal pathogen in children, and that a large proportion of pediatric CDI cases are community acquired. Many cases appear to be occurring without the exposure to antimicrobial drugs that has typically been a risk factor for CDI, they said, noting that the BI/NAP1/027 strain likely is related to these changes in pediatric CDI epidemiology; at least two reports show it has a prevalence of up to 38% in pediatric CDI populations, and it is associated with a fourfold increase in complication rates, compared with other strains.

To better characterize the epidemiology, the investigators performed a time-series analysis using information from the Kids' Inpatient Database (KID) of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project, which includes data from more than 3,700 hospitals in 38 states, and from the Centers for Disease Control and Prevention's National Hospital Discharge Survey, which includes information from about 500 noninstitutional, nonfederal, short-stay hospitals in the United States. The latter analysis allowed for cross-sectional characterization of all CDI hospitalizations, including separate analysis of newborn data not available from the KID.

In addition to the finding of an increasing rate of CDI-related hospitalizations in children, the investigators also found a similar increase in rotavirus-related hospitalizations.

Additional study is urgently needed to help better define the epidemiology of CDI, the investigators said, noting a particular need for more information about its role in the pathogenesis of disease in those under age 1 year who are not newborns. Laboratory testing for CDI is not routinely performed in those under age 1 year, because of their typically low rate of clinical disease and high rate of C. difficile carriage, and it remains unclear whether the relatively high rate of CDI-related hospitalizations in this group is a reflection of true disease or colonization, as a pathogenic role of C. difficile could not be definitively determined in this study, Dr. Zilberberg and her associates said.

Major Finding: Women with EC on hand were no less likely to become pregnant than those who had “standard access.” Odds ratios for becoming pregnant ranged from 0.48 to 0.98 for studies with follow-up ranging from 3 months to 12 months.

Data Source: A meta-analysis of 11 randomized controlled trials involving 7,695 women from the United States, China, India, and Sweden.

Disclosures: Two of the Cochrane Review authors were also investigators involved in studies that were included in the review. Ibis Reproductive Health provided support for this study.

Advance provision of emergency contraception is associated with earlier use and increased overall use of EC following unprotected sex, but it does not reduce pregnancy rates, according to the findings of an updated Cochrane Review.

Eleven randomized controlled trials involving 7,695 women from the United States, China, India, and Sweden were included in the new review, which is an updated version of a review completed in 2007 with similar findings.

Women in the 11 trials who had EC on hand were no less likely to become pregnant than those who had “standard access,” such as counseling and/or access on request, lead researcher Chelsea Polis of Johns Hopkins University, Baltimore, and her colleagues reported online in the Cochrane Database for Systematic Reviews. Odds ratios ranged from 0.48 to 0.98 for studies with follow-up ranging from 3 months to 12 months, respectively.

Compared with those who had standard access, the women with advance access did use EC more often (odds ratio 2.47 for single use and 4.13 for multiple use), and they used it earlier (weighted mean average of 12.98 hours earlier). They also were no more likely to contract a sexually transmitted infection (OR 1.01).

Condom use was the same among those with and without advance access, the investigators found.

Providing EC in advance of need is a common strategy for ensuring that women have access to EC when they need it, but despite earlier optimistic projections of the potential public health impact of improved access, the findings of this review suggest this approach does not reduce unintended pregnancy, Ms. Polis and her associates reported.

Part of the problem is that some women do not use EC even when it is available. Non-use varied widely across the studies included in the review, and research suggests that a number of factors contribute to the decision to not use EC, including unperceived pregnancy risk, concerns about side effects, and inconvenience, the investigators noted.

Nonetheless, the findings should not preclude women from being provided with advance access to EC, particularly since obtaining EC when needed can be difficult and time-consuming, and because the review suggests that advance access does not negatively impact sexual and reproductive health behaviors and outcomes, they said.

“Women should be given information about and easy access to emergency contraception because individual women can decrease their chances of pregnancy by using this method,” Ms. Polis and her associates concluded.

Future research should focus on the reasons behind failure to use EC when needed and available, they said.

Emergency contraception methods included in this review were combined estrogen-progestin, levonorgestrel alone, and mifepristone. None of the studies in the review that compared the regimens showed any difference in outcomes based on method used.

Weaknesses of the review include the unknown validity of reported information on the use of EC, the frequency of unprotected sex, and changes in contraceptive patterns. This information should be viewed with caution, given the lack of objective verification, the investigators said.

Major Finding: Women with EC on hand were no less likely to become pregnant than those who had “standard access.” Odds ratios for becoming pregnant ranged from 0.48 to 0.98 for studies with follow-up ranging from 3 months to 12 months.

Data Source: A meta-analysis of 11 randomized controlled trials involving 7,695 women from the United States, China, India, and Sweden.

Disclosures: Two of the Cochrane Review authors were also investigators involved in studies that were included in the review. Ibis Reproductive Health provided support for this study.

Advance provision of emergency contraception is associated with earlier use and increased overall use of EC following unprotected sex, but it does not reduce pregnancy rates, according to the findings of an updated Cochrane Review.

Eleven randomized controlled trials involving 7,695 women from the United States, China, India, and Sweden were included in the new review, which is an updated version of a review completed in 2007 with similar findings.

Women in the 11 trials who had EC on hand were no less likely to become pregnant than those who had “standard access,” such as counseling and/or access on request, lead researcher Chelsea Polis of Johns Hopkins University, Baltimore, and her colleagues reported online in the Cochrane Database for Systematic Reviews. Odds ratios ranged from 0.48 to 0.98 for studies with follow-up ranging from 3 months to 12 months, respectively.

Compared with those who had standard access, the women with advance access did use EC more often (odds ratio 2.47 for single use and 4.13 for multiple use), and they used it earlier (weighted mean average of 12.98 hours earlier). They also were no more likely to contract a sexually transmitted infection (OR 1.01).

Condom use was the same among those with and without advance access, the investigators found.

Providing EC in advance of need is a common strategy for ensuring that women have access to EC when they need it, but despite earlier optimistic projections of the potential public health impact of improved access, the findings of this review suggest this approach does not reduce unintended pregnancy, Ms. Polis and her associates reported.

Part of the problem is that some women do not use EC even when it is available. Non-use varied widely across the studies included in the review, and research suggests that a number of factors contribute to the decision to not use EC, including unperceived pregnancy risk, concerns about side effects, and inconvenience, the investigators noted.

Nonetheless, the findings should not preclude women from being provided with advance access to EC, particularly since obtaining EC when needed can be difficult and time-consuming, and because the review suggests that advance access does not negatively impact sexual and reproductive health behaviors and outcomes, they said.

“Women should be given information about and easy access to emergency contraception because individual women can decrease their chances of pregnancy by using this method,” Ms. Polis and her associates concluded.

Future research should focus on the reasons behind failure to use EC when needed and available, they said.

Emergency contraception methods included in this review were combined estrogen-progestin, levonorgestrel alone, and mifepristone. None of the studies in the review that compared the regimens showed any difference in outcomes based on method used.

Weaknesses of the review include the unknown validity of reported information on the use of EC, the frequency of unprotected sex, and changes in contraceptive patterns. This information should be viewed with caution, given the lack of objective verification, the investigators said.

Major Finding: Women with EC on hand were no less likely to become pregnant than those who had “standard access.” Odds ratios for becoming pregnant ranged from 0.48 to 0.98 for studies with follow-up ranging from 3 months to 12 months.

Data Source: A meta-analysis of 11 randomized controlled trials involving 7,695 women from the United States, China, India, and Sweden.

Disclosures: Two of the Cochrane Review authors were also investigators involved in studies that were included in the review. Ibis Reproductive Health provided support for this study.

Advance provision of emergency contraception is associated with earlier use and increased overall use of EC following unprotected sex, but it does not reduce pregnancy rates, according to the findings of an updated Cochrane Review.

Eleven randomized controlled trials involving 7,695 women from the United States, China, India, and Sweden were included in the new review, which is an updated version of a review completed in 2007 with similar findings.

Women in the 11 trials who had EC on hand were no less likely to become pregnant than those who had “standard access,” such as counseling and/or access on request, lead researcher Chelsea Polis of Johns Hopkins University, Baltimore, and her colleagues reported online in the Cochrane Database for Systematic Reviews. Odds ratios ranged from 0.48 to 0.98 for studies with follow-up ranging from 3 months to 12 months, respectively.

Compared with those who had standard access, the women with advance access did use EC more often (odds ratio 2.47 for single use and 4.13 for multiple use), and they used it earlier (weighted mean average of 12.98 hours earlier). They also were no more likely to contract a sexually transmitted infection (OR 1.01).

Condom use was the same among those with and without advance access, the investigators found.

Providing EC in advance of need is a common strategy for ensuring that women have access to EC when they need it, but despite earlier optimistic projections of the potential public health impact of improved access, the findings of this review suggest this approach does not reduce unintended pregnancy, Ms. Polis and her associates reported.

Part of the problem is that some women do not use EC even when it is available. Non-use varied widely across the studies included in the review, and research suggests that a number of factors contribute to the decision to not use EC, including unperceived pregnancy risk, concerns about side effects, and inconvenience, the investigators noted.

Nonetheless, the findings should not preclude women from being provided with advance access to EC, particularly since obtaining EC when needed can be difficult and time-consuming, and because the review suggests that advance access does not negatively impact sexual and reproductive health behaviors and outcomes, they said.

“Women should be given information about and easy access to emergency contraception because individual women can decrease their chances of pregnancy by using this method,” Ms. Polis and her associates concluded.

Future research should focus on the reasons behind failure to use EC when needed and available, they said.

Emergency contraception methods included in this review were combined estrogen-progestin, levonorgestrel alone, and mifepristone. None of the studies in the review that compared the regimens showed any difference in outcomes based on method used.

Weaknesses of the review include the unknown validity of reported information on the use of EC, the frequency of unprotected sex, and changes in contraceptive patterns. This information should be viewed with caution, given the lack of objective verification, the investigators said.

Major Finding: Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively).

Data Source: A large, retrospective, case-control study of 7,404 children with psoriasis under age 18 years and 37,020 controls.

Disclosures: Abbott Laboratories sponsored the study.

MIAMI — Children with psoriasis have a significantly greater risk of developing a psychiatric disorder than those without psoriasis, according to findings from a large, retrospective, case-control study.

Nationally representative health plan data for 7,404 children under the age of 18 years who had psoriasis found that 5.1% were diagnosed with or treated for a psychiatric disorder after health plan enrollment, compared with 4.1% of 37,020 controls.

Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively), Carol Bao, Ph.D., said in a poster presented at the annual meeting of the American Academy of Dermatology.

For children with psoriasis, the estimated hazard ratio for developing any psychiatric disorder was 1.25, for developing depression was 1.23, and for developing anxiety was 1.32, said Dr. Bao, a senior manager at Abbott Laboratories, Chicago.

The investigators also looked at prescriptions for psychotropic medications in assessing risk for development of psychiatric disorders.

Prescriptions can be a marker for a diagnosis in cases where the prescribing physician may be hesitant to refer the patient or make a diagnosis, Dr. Bao explained, noting that this helped correct for possible underestimation of the development of psychiatric disorders and provided a risk estimate range.

When both diagnoses and prescriptions were considered, psoriasis patients had 25%–47% greater risk of developing a psychiatric disorder, 23%–62% greater risk of developing depression, and 32%–250% greater risk of developing anxiety, compared with controls, Dr. Bao said.

Patients included in the study had a mean age of 11.4 years. They were selected from a database of health plan participants who were enrolled in a plan at least 6 months before and after the first psoriasis diagnosis date (the index date), and who were followed from the index date until they were first diagnosed with any psychiatric disorder or were prescribed a drug used for the treatment of a psychiatric disorder. Any plan participant with a pre-enrollment psychiatric diagnosis or prescription was excluded.

Controls were matched to patients based on age, sex, and index date.

The findings of an increased risk of developing psychiatric disorders in case patients remained significant after controlling for age, sex, health plan, region of residence, and comorbidities, Dr. Bao noted.

The study is limited by the potential for coding and reporting errors in the data used and by lack of information on the severity of the psychiatric disorders. However, the findings do suggest that the psychiatric impact of psoriasis on children must be addressed because of the potential for both short-and long-term adverse effects.

“If we put these data in perspective, the development of psychiatric disorders at a young age can have a great impact in future adult life,” she said.

Major Finding: Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively).

Data Source: A large, retrospective, case-control study of 7,404 children with psoriasis under age 18 years and 37,020 controls.

Disclosures: Abbott Laboratories sponsored the study.

MIAMI — Children with psoriasis have a significantly greater risk of developing a psychiatric disorder than those without psoriasis, according to findings from a large, retrospective, case-control study.

Nationally representative health plan data for 7,404 children under the age of 18 years who had psoriasis found that 5.1% were diagnosed with or treated for a psychiatric disorder after health plan enrollment, compared with 4.1% of 37,020 controls.

Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively), Carol Bao, Ph.D., said in a poster presented at the annual meeting of the American Academy of Dermatology.

For children with psoriasis, the estimated hazard ratio for developing any psychiatric disorder was 1.25, for developing depression was 1.23, and for developing anxiety was 1.32, said Dr. Bao, a senior manager at Abbott Laboratories, Chicago.

The investigators also looked at prescriptions for psychotropic medications in assessing risk for development of psychiatric disorders.

Prescriptions can be a marker for a diagnosis in cases where the prescribing physician may be hesitant to refer the patient or make a diagnosis, Dr. Bao explained, noting that this helped correct for possible underestimation of the development of psychiatric disorders and provided a risk estimate range.

When both diagnoses and prescriptions were considered, psoriasis patients had 25%–47% greater risk of developing a psychiatric disorder, 23%–62% greater risk of developing depression, and 32%–250% greater risk of developing anxiety, compared with controls, Dr. Bao said.

Patients included in the study had a mean age of 11.4 years. They were selected from a database of health plan participants who were enrolled in a plan at least 6 months before and after the first psoriasis diagnosis date (the index date), and who were followed from the index date until they were first diagnosed with any psychiatric disorder or were prescribed a drug used for the treatment of a psychiatric disorder. Any plan participant with a pre-enrollment psychiatric diagnosis or prescription was excluded.

Controls were matched to patients based on age, sex, and index date.

The findings of an increased risk of developing psychiatric disorders in case patients remained significant after controlling for age, sex, health plan, region of residence, and comorbidities, Dr. Bao noted.

The study is limited by the potential for coding and reporting errors in the data used and by lack of information on the severity of the psychiatric disorders. However, the findings do suggest that the psychiatric impact of psoriasis on children must be addressed because of the potential for both short-and long-term adverse effects.

“If we put these data in perspective, the development of psychiatric disorders at a young age can have a great impact in future adult life,” she said.

Major Finding: Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively).

Data Source: A large, retrospective, case-control study of 7,404 children with psoriasis under age 18 years and 37,020 controls.

Disclosures: Abbott Laboratories sponsored the study.

MIAMI — Children with psoriasis have a significantly greater risk of developing a psychiatric disorder than those without psoriasis, according to findings from a large, retrospective, case-control study.

Nationally representative health plan data for 7,404 children under the age of 18 years who had psoriasis found that 5.1% were diagnosed with or treated for a psychiatric disorder after health plan enrollment, compared with 4.1% of 37,020 controls.

Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively), Carol Bao, Ph.D., said in a poster presented at the annual meeting of the American Academy of Dermatology.

For children with psoriasis, the estimated hazard ratio for developing any psychiatric disorder was 1.25, for developing depression was 1.23, and for developing anxiety was 1.32, said Dr. Bao, a senior manager at Abbott Laboratories, Chicago.

The investigators also looked at prescriptions for psychotropic medications in assessing risk for development of psychiatric disorders.

Prescriptions can be a marker for a diagnosis in cases where the prescribing physician may be hesitant to refer the patient or make a diagnosis, Dr. Bao explained, noting that this helped correct for possible underestimation of the development of psychiatric disorders and provided a risk estimate range.

When both diagnoses and prescriptions were considered, psoriasis patients had 25%–47% greater risk of developing a psychiatric disorder, 23%–62% greater risk of developing depression, and 32%–250% greater risk of developing anxiety, compared with controls, Dr. Bao said.

Patients included in the study had a mean age of 11.4 years. They were selected from a database of health plan participants who were enrolled in a plan at least 6 months before and after the first psoriasis diagnosis date (the index date), and who were followed from the index date until they were first diagnosed with any psychiatric disorder or were prescribed a drug used for the treatment of a psychiatric disorder. Any plan participant with a pre-enrollment psychiatric diagnosis or prescription was excluded.

Controls were matched to patients based on age, sex, and index date.

The findings of an increased risk of developing psychiatric disorders in case patients remained significant after controlling for age, sex, health plan, region of residence, and comorbidities, Dr. Bao noted.

The study is limited by the potential for coding and reporting errors in the data used and by lack of information on the severity of the psychiatric disorders. However, the findings do suggest that the psychiatric impact of psoriasis on children must be addressed because of the potential for both short-and long-term adverse effects.

“If we put these data in perspective, the development of psychiatric disorders at a young age can have a great impact in future adult life,” she said.