Nancy Walsh

NOORDWIJK, NETHERLANDS — The list of risk factors associated with the development of metastases in melanoma should be expanded by two, Jeremy Brauer wrote in a prizewinning poster presented at a conference on melanoma sponsored by Imedex Inc.

In a nested case-control study of melanoma patients presenting with only local disease between 1972 and 2005, the investigators found an odds ratio of 1.95 for the development of metastases in patients with a past history of nonmelanoma skin cancer and an odds ratio of 2.51 for cancer other than skin, said Mr. Brauer, a fellow in the department of dermatology at the University of Pennsylvania, Philadelphia.

Previously identified risk factors for metastatic disease include male gender, body site, Breslow thickness, Clark's level, vertical growth phase, microscopic satellites, and ulceration.

The study included 549 patients who developed metastases at least 6 months after definitive excision. For each case, there was a control patient with melanoma who did not develop metastases. Aside from the two new factors, multivariate analyses confirmed that patients who developed metastases were more likely to be male, to have lesions of greater thickness, and to have lesions characterized by ulceration.

The study also revealed that differences may exist in risk factors for early versus late metastases. “Although previous investigations have found that between 65% and 81% of melanoma metastases will occur within 3 years, metastases may occur at any time, even 10 or more years later,” Mr. Brauer wrote.

Various time intervals following diagnosis have been seen in other cancers, such as gastric carcinoma (Cancer 2000;89:255–61). “However, to the best of our knowledge no prior study of early versus late metastases has been performed that examined a large number of clinical and tumor characteristics,” wrote Mr. Brauer.

A total of 320 patients developed their first metastasis within 3 years after surgery; these were classified as early metastases. In 70 patients, metastases did not develop until after 8 years; these were termed late metastases. Patients with early metastasis were more likely to have lesions of greater thickness, with an odds ratio of 2.35, and to have ulcerated lesions, with an odds ratio of 3.58.

The early metastasis patients also were more likely to have a past medical history of nonmelanoma skin cancer, compared with late metastasis patients. The odds ratio associated with this last factor was 4.83.

“Identification of these risk factors is important in gaining a better understanding of disease progression for the purposes of risk stratification in clinical trials and for patient management and treatment,” Mr. Bauer explained.

NOORDWIJK, NETHERLANDS — The list of risk factors associated with the development of metastases in melanoma should be expanded by two, Jeremy Brauer wrote in a prizewinning poster presented at a conference on melanoma sponsored by Imedex Inc.

In a nested case-control study of melanoma patients presenting with only local disease between 1972 and 2005, the investigators found an odds ratio of 1.95 for the development of metastases in patients with a past history of nonmelanoma skin cancer and an odds ratio of 2.51 for cancer other than skin, said Mr. Brauer, a fellow in the department of dermatology at the University of Pennsylvania, Philadelphia.

Previously identified risk factors for metastatic disease include male gender, body site, Breslow thickness, Clark's level, vertical growth phase, microscopic satellites, and ulceration.

The study included 549 patients who developed metastases at least 6 months after definitive excision. For each case, there was a control patient with melanoma who did not develop metastases. Aside from the two new factors, multivariate analyses confirmed that patients who developed metastases were more likely to be male, to have lesions of greater thickness, and to have lesions characterized by ulceration.

The study also revealed that differences may exist in risk factors for early versus late metastases. “Although previous investigations have found that between 65% and 81% of melanoma metastases will occur within 3 years, metastases may occur at any time, even 10 or more years later,” Mr. Brauer wrote.

Various time intervals following diagnosis have been seen in other cancers, such as gastric carcinoma (Cancer 2000;89:255–61). “However, to the best of our knowledge no prior study of early versus late metastases has been performed that examined a large number of clinical and tumor characteristics,” wrote Mr. Brauer.

A total of 320 patients developed their first metastasis within 3 years after surgery; these were classified as early metastases. In 70 patients, metastases did not develop until after 8 years; these were termed late metastases. Patients with early metastasis were more likely to have lesions of greater thickness, with an odds ratio of 2.35, and to have ulcerated lesions, with an odds ratio of 3.58.

The early metastasis patients also were more likely to have a past medical history of nonmelanoma skin cancer, compared with late metastasis patients. The odds ratio associated with this last factor was 4.83.

“Identification of these risk factors is important in gaining a better understanding of disease progression for the purposes of risk stratification in clinical trials and for patient management and treatment,” Mr. Bauer explained.

NOORDWIJK, NETHERLANDS — The list of risk factors associated with the development of metastases in melanoma should be expanded by two, Jeremy Brauer wrote in a prizewinning poster presented at a conference on melanoma sponsored by Imedex Inc.

In a nested case-control study of melanoma patients presenting with only local disease between 1972 and 2005, the investigators found an odds ratio of 1.95 for the development of metastases in patients with a past history of nonmelanoma skin cancer and an odds ratio of 2.51 for cancer other than skin, said Mr. Brauer, a fellow in the department of dermatology at the University of Pennsylvania, Philadelphia.

Previously identified risk factors for metastatic disease include male gender, body site, Breslow thickness, Clark's level, vertical growth phase, microscopic satellites, and ulceration.

The study included 549 patients who developed metastases at least 6 months after definitive excision. For each case, there was a control patient with melanoma who did not develop metastases. Aside from the two new factors, multivariate analyses confirmed that patients who developed metastases were more likely to be male, to have lesions of greater thickness, and to have lesions characterized by ulceration.

The study also revealed that differences may exist in risk factors for early versus late metastases. “Although previous investigations have found that between 65% and 81% of melanoma metastases will occur within 3 years, metastases may occur at any time, even 10 or more years later,” Mr. Brauer wrote.

Various time intervals following diagnosis have been seen in other cancers, such as gastric carcinoma (Cancer 2000;89:255–61). “However, to the best of our knowledge no prior study of early versus late metastases has been performed that examined a large number of clinical and tumor characteristics,” wrote Mr. Brauer.

A total of 320 patients developed their first metastasis within 3 years after surgery; these were classified as early metastases. In 70 patients, metastases did not develop until after 8 years; these were termed late metastases. Patients with early metastasis were more likely to have lesions of greater thickness, with an odds ratio of 2.35, and to have ulcerated lesions, with an odds ratio of 3.58.

The early metastasis patients also were more likely to have a past medical history of nonmelanoma skin cancer, compared with late metastasis patients. The odds ratio associated with this last factor was 4.83.

“Identification of these risk factors is important in gaining a better understanding of disease progression for the purposes of risk stratification in clinical trials and for patient management and treatment,” Mr. Bauer explained.

Breast-feeding has little or no effect on children's later intelligence, according to the largest study ever to address this question.

The influence of breast-feeding on cognitive ability has been debated for more than 70 years, with multiple potentially confounding factors having been identified. These include socioeconomic status, birth weight, maternal history of smoking, maternal and paternal education, and race or ethnicity. Maternal intelligence, however, has largely been overlooked as a potential confounder in studies investigating the effects of breast-feeding, according to Geoff Der, a statistician at the Medical Research Council's Social and Public Health Sciences Unit in Glasgow, Scotland.

Analyzing data from 5,475 children and their mothers in the population-based U.S. national longitudinal survey of youth that began in 1979, Mr. Der and his colleagues found that if maternal intelligence was not included as a potential confounder, breast-feeding did appear to exert beneficial effects on children's intelligence, adding approximately 4 points. However, when maternal intelligence was included in the analysis, breast-feeding was associated with an increase of less than half a point (BMJ 2006 Oct. 4 [doi:10.1136/bmj.38978.699583.55]). Previous studies' not having considered maternal intelligence was “surprising given the heritability of intelligence,” he observed.

The researchers also determined that an increase of 15 points in maternal intelligence more than doubled the likelihood that the child would be breast-fed. They furthermore observed that mothers who breast-fed tended to be older and more educated, and to provide a more stimulating home environment.

Despite the lack of association with children's intelligence, breast-feeding remains important for overall growth and development, Mr. Der noted.

Breast-feeding has little or no effect on children's later intelligence, according to the largest study ever to address this question.

The influence of breast-feeding on cognitive ability has been debated for more than 70 years, with multiple potentially confounding factors having been identified. These include socioeconomic status, birth weight, maternal history of smoking, maternal and paternal education, and race or ethnicity. Maternal intelligence, however, has largely been overlooked as a potential confounder in studies investigating the effects of breast-feeding, according to Geoff Der, a statistician at the Medical Research Council's Social and Public Health Sciences Unit in Glasgow, Scotland.

Analyzing data from 5,475 children and their mothers in the population-based U.S. national longitudinal survey of youth that began in 1979, Mr. Der and his colleagues found that if maternal intelligence was not included as a potential confounder, breast-feeding did appear to exert beneficial effects on children's intelligence, adding approximately 4 points. However, when maternal intelligence was included in the analysis, breast-feeding was associated with an increase of less than half a point (BMJ 2006 Oct. 4 [doi:10.1136/bmj.38978.699583.55]). Previous studies' not having considered maternal intelligence was “surprising given the heritability of intelligence,” he observed.

The researchers also determined that an increase of 15 points in maternal intelligence more than doubled the likelihood that the child would be breast-fed. They furthermore observed that mothers who breast-fed tended to be older and more educated, and to provide a more stimulating home environment.

Despite the lack of association with children's intelligence, breast-feeding remains important for overall growth and development, Mr. Der noted.

Breast-feeding has little or no effect on children's later intelligence, according to the largest study ever to address this question.

The influence of breast-feeding on cognitive ability has been debated for more than 70 years, with multiple potentially confounding factors having been identified. These include socioeconomic status, birth weight, maternal history of smoking, maternal and paternal education, and race or ethnicity. Maternal intelligence, however, has largely been overlooked as a potential confounder in studies investigating the effects of breast-feeding, according to Geoff Der, a statistician at the Medical Research Council's Social and Public Health Sciences Unit in Glasgow, Scotland.

Analyzing data from 5,475 children and their mothers in the population-based U.S. national longitudinal survey of youth that began in 1979, Mr. Der and his colleagues found that if maternal intelligence was not included as a potential confounder, breast-feeding did appear to exert beneficial effects on children's intelligence, adding approximately 4 points. However, when maternal intelligence was included in the analysis, breast-feeding was associated with an increase of less than half a point (BMJ 2006 Oct. 4 [doi:10.1136/bmj.38978.699583.55]). Previous studies' not having considered maternal intelligence was “surprising given the heritability of intelligence,” he observed.

The researchers also determined that an increase of 15 points in maternal intelligence more than doubled the likelihood that the child would be breast-fed. They furthermore observed that mothers who breast-fed tended to be older and more educated, and to provide a more stimulating home environment.

Despite the lack of association with children's intelligence, breast-feeding remains important for overall growth and development, Mr. Der noted.

AMSTERDAM — Reassuring data on the use of etanercept in patients with juvenile idiopathic arthritis are emerging from a multicenter Spanish registry, with significant improvements being seen on all clinical parameters and no serious adverse events being reported, Dr. Inmaculada Calvo said at the annual European Congress of Rheumatology.

Etanercept was approved for the treatment of JIA in 1999, but few phase IV studies have been done evaluating the long-term safety and efficacy of tumor necrosis factor (TNF)-αblockade in these patients, noted Dr. Calvo.

A total of 103 patients have been enrolled in the registry, with follow-up extending as long as 48 months.

Fifty-three of the patients were female, the median patient age was 12.3 years, and the median age at disease onset was 5.6 years. During the 3 years prior to recruitment, 91.6% had undergone treatment with methotrexate but had shown an inadequate response, according to Dr. Calvo of the Hospital Infantil la Fe, Valencia, Spain. All patients had polyarticular disease, 55.3% were seronegative, and 15.5% had systemic-onset disease.

At the time of analysis, 83 patients (80.6%) had been followed for at least 6 months, 72 (69.9%) had been followed for 12 months, and 49 (47.6%) had been followed for 24 months. In addition, 29 (28.2%) and 15 (14.6%) had been followed for 36 and 48 months, respectively.

No serious adverse events have been observed, and the infections reported were typical for patients of this age (see box).

The median number of tender joints and swollen joints decreased from 9.09 to 0.3 and 9.24 to 3.13, respectively, Dr. Calvo wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.

Physician global assessment decreased from a median of 5.96 to 1.13, and patient global assessment fell from a median of 5.43 to 1.30.

The Childhood Health Assessment Questionnaire index also decreased, from a median of 1.61 to 0.44.

Furthermore, laboratory parameters improved, with the erythrocyte sedimentation rate falling from 43 to 11 mm/h and C-reactive protein level decreasing from 12 to 0.1 mg/L.

These data provide further support for the use of etanercept in JIA, Dr. Calvo concluded.

Reported Etanercept Adverse Events

AMSTERDAM — Reassuring data on the use of etanercept in patients with juvenile idiopathic arthritis are emerging from a multicenter Spanish registry, with significant improvements being seen on all clinical parameters and no serious adverse events being reported, Dr. Inmaculada Calvo said at the annual European Congress of Rheumatology.

Etanercept was approved for the treatment of JIA in 1999, but few phase IV studies have been done evaluating the long-term safety and efficacy of tumor necrosis factor (TNF)-αblockade in these patients, noted Dr. Calvo.

A total of 103 patients have been enrolled in the registry, with follow-up extending as long as 48 months.

Fifty-three of the patients were female, the median patient age was 12.3 years, and the median age at disease onset was 5.6 years. During the 3 years prior to recruitment, 91.6% had undergone treatment with methotrexate but had shown an inadequate response, according to Dr. Calvo of the Hospital Infantil la Fe, Valencia, Spain. All patients had polyarticular disease, 55.3% were seronegative, and 15.5% had systemic-onset disease.

At the time of analysis, 83 patients (80.6%) had been followed for at least 6 months, 72 (69.9%) had been followed for 12 months, and 49 (47.6%) had been followed for 24 months. In addition, 29 (28.2%) and 15 (14.6%) had been followed for 36 and 48 months, respectively.

No serious adverse events have been observed, and the infections reported were typical for patients of this age (see box).

The median number of tender joints and swollen joints decreased from 9.09 to 0.3 and 9.24 to 3.13, respectively, Dr. Calvo wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.

Physician global assessment decreased from a median of 5.96 to 1.13, and patient global assessment fell from a median of 5.43 to 1.30.

The Childhood Health Assessment Questionnaire index also decreased, from a median of 1.61 to 0.44.

Furthermore, laboratory parameters improved, with the erythrocyte sedimentation rate falling from 43 to 11 mm/h and C-reactive protein level decreasing from 12 to 0.1 mg/L.

These data provide further support for the use of etanercept in JIA, Dr. Calvo concluded.

Reported Etanercept Adverse Events

AMSTERDAM — Reassuring data on the use of etanercept in patients with juvenile idiopathic arthritis are emerging from a multicenter Spanish registry, with significant improvements being seen on all clinical parameters and no serious adverse events being reported, Dr. Inmaculada Calvo said at the annual European Congress of Rheumatology.

Etanercept was approved for the treatment of JIA in 1999, but few phase IV studies have been done evaluating the long-term safety and efficacy of tumor necrosis factor (TNF)-αblockade in these patients, noted Dr. Calvo.

A total of 103 patients have been enrolled in the registry, with follow-up extending as long as 48 months.

Fifty-three of the patients were female, the median patient age was 12.3 years, and the median age at disease onset was 5.6 years. During the 3 years prior to recruitment, 91.6% had undergone treatment with methotrexate but had shown an inadequate response, according to Dr. Calvo of the Hospital Infantil la Fe, Valencia, Spain. All patients had polyarticular disease, 55.3% were seronegative, and 15.5% had systemic-onset disease.

At the time of analysis, 83 patients (80.6%) had been followed for at least 6 months, 72 (69.9%) had been followed for 12 months, and 49 (47.6%) had been followed for 24 months. In addition, 29 (28.2%) and 15 (14.6%) had been followed for 36 and 48 months, respectively.

No serious adverse events have been observed, and the infections reported were typical for patients of this age (see box).

The median number of tender joints and swollen joints decreased from 9.09 to 0.3 and 9.24 to 3.13, respectively, Dr. Calvo wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.

Physician global assessment decreased from a median of 5.96 to 1.13, and patient global assessment fell from a median of 5.43 to 1.30.

The Childhood Health Assessment Questionnaire index also decreased, from a median of 1.61 to 0.44.

Furthermore, laboratory parameters improved, with the erythrocyte sedimentation rate falling from 43 to 11 mm/h and C-reactive protein level decreasing from 12 to 0.1 mg/L.

These data provide further support for the use of etanercept in JIA, Dr. Calvo concluded.

Reported Etanercept Adverse Events

An 81-year-old man presented with severe proximal muscle pain, reduced mobility, and a history of frequent falls as well as knee osteoarthritis, hypertension, and a vertebral wedge collapse nearly 2 decades earlier. Clinical examination revealed ankle swelling and left knee synovitis, as well as bilateral quadriceps muscle wasting and grade 4 or 5 muscle power.

Scintigraphy showed the Lone Ranger sign, with increased uptake in the skull and around the eyes and reduced soft tissue activity. Laboratory evaluations identified and elevated calcium level, at 4.02 mmol/L, and an elevated alkaline phosphate level, at 782 U/L, which suggested severe bone disease.

Diagnosis

The diagnosis, based on scintigraphy and other radiographic investigations, was long-standing parathyroid bone disease complicating primary hyperparathyroidism (Ann. Rheum. Dis. 2006;65:1244).

The scintigraphic findings were characterized as a superscan, in which there is diffuse increased skeletal uptake relating to increased bone turnover and which can appear to be a negative or normal scan. This appearance is more common in metastatic cancer and is quite unusual in hyperparathyroid bone disease, according to Dr. D. John Pradeep of Norfolk and Norwich University Hospital, Norwich, England.

Hyperparathyroidism itself today is usually detected quite early, and a presentation such as this, with extensive bone disease, is quite rare, Dr. Pradeep said in an interview. Aside from the scintigraphic findings, hyperparathyroidism also is characterized by x-ray findings of brown tumors, which are small lytic lesions of the hip.

Further diagnostic evaluation of this patient using ultrasound and Tc-99m sestamibi scanning identified a mass by the left upper pole of the thyroid. The tumor was removed by minimally invasive parathyroidectomy, and histologically was found to be a benign adenoma.

An 81-year-old man presented with severe proximal muscle pain, reduced mobility, and a history of frequent falls as well as knee osteoarthritis, hypertension, and a vertebral wedge collapse nearly 2 decades earlier. Clinical examination revealed ankle swelling and left knee synovitis, as well as bilateral quadriceps muscle wasting and grade 4 or 5 muscle power.

Scintigraphy showed the Lone Ranger sign, with increased uptake in the skull and around the eyes and reduced soft tissue activity. Laboratory evaluations identified and elevated calcium level, at 4.02 mmol/L, and an elevated alkaline phosphate level, at 782 U/L, which suggested severe bone disease.

Diagnosis

The diagnosis, based on scintigraphy and other radiographic investigations, was long-standing parathyroid bone disease complicating primary hyperparathyroidism (Ann. Rheum. Dis. 2006;65:1244).

The scintigraphic findings were characterized as a superscan, in which there is diffuse increased skeletal uptake relating to increased bone turnover and which can appear to be a negative or normal scan. This appearance is more common in metastatic cancer and is quite unusual in hyperparathyroid bone disease, according to Dr. D. John Pradeep of Norfolk and Norwich University Hospital, Norwich, England.

Hyperparathyroidism itself today is usually detected quite early, and a presentation such as this, with extensive bone disease, is quite rare, Dr. Pradeep said in an interview. Aside from the scintigraphic findings, hyperparathyroidism also is characterized by x-ray findings of brown tumors, which are small lytic lesions of the hip.

Further diagnostic evaluation of this patient using ultrasound and Tc-99m sestamibi scanning identified a mass by the left upper pole of the thyroid. The tumor was removed by minimally invasive parathyroidectomy, and histologically was found to be a benign adenoma.

An 81-year-old man presented with severe proximal muscle pain, reduced mobility, and a history of frequent falls as well as knee osteoarthritis, hypertension, and a vertebral wedge collapse nearly 2 decades earlier. Clinical examination revealed ankle swelling and left knee synovitis, as well as bilateral quadriceps muscle wasting and grade 4 or 5 muscle power.

Scintigraphy showed the Lone Ranger sign, with increased uptake in the skull and around the eyes and reduced soft tissue activity. Laboratory evaluations identified and elevated calcium level, at 4.02 mmol/L, and an elevated alkaline phosphate level, at 782 U/L, which suggested severe bone disease.

Diagnosis

The diagnosis, based on scintigraphy and other radiographic investigations, was long-standing parathyroid bone disease complicating primary hyperparathyroidism (Ann. Rheum. Dis. 2006;65:1244).

The scintigraphic findings were characterized as a superscan, in which there is diffuse increased skeletal uptake relating to increased bone turnover and which can appear to be a negative or normal scan. This appearance is more common in metastatic cancer and is quite unusual in hyperparathyroid bone disease, according to Dr. D. John Pradeep of Norfolk and Norwich University Hospital, Norwich, England.

Hyperparathyroidism itself today is usually detected quite early, and a presentation such as this, with extensive bone disease, is quite rare, Dr. Pradeep said in an interview. Aside from the scintigraphic findings, hyperparathyroidism also is characterized by x-ray findings of brown tumors, which are small lytic lesions of the hip.

Further diagnostic evaluation of this patient using ultrasound and Tc-99m sestamibi scanning identified a mass by the left upper pole of the thyroid. The tumor was removed by minimally invasive parathyroidectomy, and histologically was found to be a benign adenoma.

MANCHESTER, ENGLAND — For the first time, a patient being treated with adalimumab for rheumatoid arthritis has developed a subepidermal pustular eruption, wrote Dr. Preeti Athavale in a poster session at the annual meeting of the British Association of Dermatologists.

Cutaneous reactions have been reported previously for the anti-tumor necrosis factor (TNF)-α agents, including injection site reactions and systemic reactions that occur during infusions. However, it had been expected that adalimumab would have fewer side effects than its predecessors, according to Dr. Athavale, of the department of dermatology at Chesterfield (England) Royal Hospital.

The 37-year-old patient had had debilitating rheumatoid arthritis for 20 years, but had no history of skin disease. She had previously received treatment with cyclosporine, infliximab, and etanercept without success. About 8 months after she began taking adalimumab, she developed painful, itchy pustules on her arms, thighs, and chest. These flared approximately 2 days after she received her twice-monthly adalimumab injection and never entirely cleared, said Dr. Athavale.

Biopsy of a pustule and adjacent skin on the arm revealed a subepidermal neutrophilic pustulosis. Immunofluorescence studies looking for evidence of immunoglobulins and complement were negative, and overall, the findings were not consistent with a primary dermatosis.

The adalimumab was stopped 3 months later for lack of efficacy, and the pustular eruption settled within 1 month. It has not recurred, Dr. Athavale reported.

There have been a few reports of skin reactions to adalimumab, mainly injection site reactions and nonspecific rashes. There also has been one case report of an erythema multiforme-like reaction that cleared when the drug was withdrawn (Arthritis Rheum. 2004;50:1690–2).

MANCHESTER, ENGLAND — For the first time, a patient being treated with adalimumab for rheumatoid arthritis has developed a subepidermal pustular eruption, wrote Dr. Preeti Athavale in a poster session at the annual meeting of the British Association of Dermatologists.

Cutaneous reactions have been reported previously for the anti-tumor necrosis factor (TNF)-α agents, including injection site reactions and systemic reactions that occur during infusions. However, it had been expected that adalimumab would have fewer side effects than its predecessors, according to Dr. Athavale, of the department of dermatology at Chesterfield (England) Royal Hospital.

The 37-year-old patient had had debilitating rheumatoid arthritis for 20 years, but had no history of skin disease. She had previously received treatment with cyclosporine, infliximab, and etanercept without success. About 8 months after she began taking adalimumab, she developed painful, itchy pustules on her arms, thighs, and chest. These flared approximately 2 days after she received her twice-monthly adalimumab injection and never entirely cleared, said Dr. Athavale.

Biopsy of a pustule and adjacent skin on the arm revealed a subepidermal neutrophilic pustulosis. Immunofluorescence studies looking for evidence of immunoglobulins and complement were negative, and overall, the findings were not consistent with a primary dermatosis.

The adalimumab was stopped 3 months later for lack of efficacy, and the pustular eruption settled within 1 month. It has not recurred, Dr. Athavale reported.

There have been a few reports of skin reactions to adalimumab, mainly injection site reactions and nonspecific rashes. There also has been one case report of an erythema multiforme-like reaction that cleared when the drug was withdrawn (Arthritis Rheum. 2004;50:1690–2).

MANCHESTER, ENGLAND — For the first time, a patient being treated with adalimumab for rheumatoid arthritis has developed a subepidermal pustular eruption, wrote Dr. Preeti Athavale in a poster session at the annual meeting of the British Association of Dermatologists.

Cutaneous reactions have been reported previously for the anti-tumor necrosis factor (TNF)-α agents, including injection site reactions and systemic reactions that occur during infusions. However, it had been expected that adalimumab would have fewer side effects than its predecessors, according to Dr. Athavale, of the department of dermatology at Chesterfield (England) Royal Hospital.

The 37-year-old patient had had debilitating rheumatoid arthritis for 20 years, but had no history of skin disease. She had previously received treatment with cyclosporine, infliximab, and etanercept without success. About 8 months after she began taking adalimumab, she developed painful, itchy pustules on her arms, thighs, and chest. These flared approximately 2 days after she received her twice-monthly adalimumab injection and never entirely cleared, said Dr. Athavale.

Biopsy of a pustule and adjacent skin on the arm revealed a subepidermal neutrophilic pustulosis. Immunofluorescence studies looking for evidence of immunoglobulins and complement were negative, and overall, the findings were not consistent with a primary dermatosis.

The adalimumab was stopped 3 months later for lack of efficacy, and the pustular eruption settled within 1 month. It has not recurred, Dr. Athavale reported.

There have been a few reports of skin reactions to adalimumab, mainly injection site reactions and nonspecific rashes. There also has been one case report of an erythema multiforme-like reaction that cleared when the drug was withdrawn (Arthritis Rheum. 2004;50:1690–2).

MANCHESTER, ENGLAND — Squamous cell carcinoma of the nail unit is often misdiagnosed and its painful course protracted because clinical features can resemble more mundane conditions such as paronychia, Dr. Mohamed Alrawi said at the annual meeting of the British Association of Dermatologists.

A retrospective study of 20 patients seen between 1997 and 2005 has identified three patterns of presentation in this rare condition, and wider recognition of these patterns could help expedite diagnosis, Dr. Alrawi said. The clinical patterns were:

▸ Type 1, in 10 (50%) patients, was a frank nodule or tumor with or without nail loss.

▸ Type 2, seen in six (30%), was a mild to moderate warty periungual lesion with nail splitting and skin fissures.

▸ Type 3, found in four (20%), was a recurrent discharge from beneath the nail with putative onychomycosis.

In all patients, less than 50% of the surface area of the distal phalanx was affected, said Dr. Alrawi of Bristol Dermatology Centre, Bristol (England) Royal Infirmary.

One patient had bone involvement. Histologic evaluation showed invasive disease in 15 patients, 5 with in situ squamous cell carcinoma. The thumb was the most commonly affected digit, involved in seven of the patients. The index finger was affected in four patients, the middle finger in three, and the ring and little fingers in one each.

A total of 14 patients reported pain as the primary symptom, and only 2 were asymptomatic, he said. In seven patients, the carcinoma was associated with human papillomavirus, with six involving type 16.

MANCHESTER, ENGLAND — Squamous cell carcinoma of the nail unit is often misdiagnosed and its painful course protracted because clinical features can resemble more mundane conditions such as paronychia, Dr. Mohamed Alrawi said at the annual meeting of the British Association of Dermatologists.

A retrospective study of 20 patients seen between 1997 and 2005 has identified three patterns of presentation in this rare condition, and wider recognition of these patterns could help expedite diagnosis, Dr. Alrawi said. The clinical patterns were:

▸ Type 1, in 10 (50%) patients, was a frank nodule or tumor with or without nail loss.

▸ Type 2, seen in six (30%), was a mild to moderate warty periungual lesion with nail splitting and skin fissures.

▸ Type 3, found in four (20%), was a recurrent discharge from beneath the nail with putative onychomycosis.

In all patients, less than 50% of the surface area of the distal phalanx was affected, said Dr. Alrawi of Bristol Dermatology Centre, Bristol (England) Royal Infirmary.

One patient had bone involvement. Histologic evaluation showed invasive disease in 15 patients, 5 with in situ squamous cell carcinoma. The thumb was the most commonly affected digit, involved in seven of the patients. The index finger was affected in four patients, the middle finger in three, and the ring and little fingers in one each.

A total of 14 patients reported pain as the primary symptom, and only 2 were asymptomatic, he said. In seven patients, the carcinoma was associated with human papillomavirus, with six involving type 16.

MANCHESTER, ENGLAND — Squamous cell carcinoma of the nail unit is often misdiagnosed and its painful course protracted because clinical features can resemble more mundane conditions such as paronychia, Dr. Mohamed Alrawi said at the annual meeting of the British Association of Dermatologists.

A retrospective study of 20 patients seen between 1997 and 2005 has identified three patterns of presentation in this rare condition, and wider recognition of these patterns could help expedite diagnosis, Dr. Alrawi said. The clinical patterns were:

▸ Type 1, in 10 (50%) patients, was a frank nodule or tumor with or without nail loss.

▸ Type 2, seen in six (30%), was a mild to moderate warty periungual lesion with nail splitting and skin fissures.

▸ Type 3, found in four (20%), was a recurrent discharge from beneath the nail with putative onychomycosis.

In all patients, less than 50% of the surface area of the distal phalanx was affected, said Dr. Alrawi of Bristol Dermatology Centre, Bristol (England) Royal Infirmary.

One patient had bone involvement. Histologic evaluation showed invasive disease in 15 patients, 5 with in situ squamous cell carcinoma. The thumb was the most commonly affected digit, involved in seven of the patients. The index finger was affected in four patients, the middle finger in three, and the ring and little fingers in one each.

A total of 14 patients reported pain as the primary symptom, and only 2 were asymptomatic, he said. In seven patients, the carcinoma was associated with human papillomavirus, with six involving type 16.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki said at a world congress on osteoporosis.

Complex dosing instructions designed to maximize bioavailability and address tolerability concerns may affect adherence to oral bisphosphonate therapy, and adherence is crucial to clinical efficacy and fracture prevention, he noted.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of symptoms such as heartburn and acid reflux. All got supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day). Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg intravenously every 3 months. The intravenous injection takes 15 to 30 seconds to complete. A total of 396 (73%) of patients chose the intravenous regimen, and 146 (27%) chose the oral route. They were permitted to switch treatment groups once during the study if they experienced adverse effects.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

In patients who chose the intravenous route of administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

So far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance; 15 went from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions. By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improvements in gastrointestinal tolerance compared with baseline.

“Patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance [seem to] prefer intravenous dosing, and patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki said. The study was sponsored by Roche Laboratories. Dr. Lewiecki made no disclosures.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki said at a world congress on osteoporosis.

Complex dosing instructions designed to maximize bioavailability and address tolerability concerns may affect adherence to oral bisphosphonate therapy, and adherence is crucial to clinical efficacy and fracture prevention, he noted.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of symptoms such as heartburn and acid reflux. All got supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day). Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg intravenously every 3 months. The intravenous injection takes 15 to 30 seconds to complete. A total of 396 (73%) of patients chose the intravenous regimen, and 146 (27%) chose the oral route. They were permitted to switch treatment groups once during the study if they experienced adverse effects.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

In patients who chose the intravenous route of administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

So far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance; 15 went from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions. By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improvements in gastrointestinal tolerance compared with baseline.

“Patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance [seem to] prefer intravenous dosing, and patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki said. The study was sponsored by Roche Laboratories. Dr. Lewiecki made no disclosures.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki said at a world congress on osteoporosis.

Complex dosing instructions designed to maximize bioavailability and address tolerability concerns may affect adherence to oral bisphosphonate therapy, and adherence is crucial to clinical efficacy and fracture prevention, he noted.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of symptoms such as heartburn and acid reflux. All got supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day). Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg intravenously every 3 months. The intravenous injection takes 15 to 30 seconds to complete. A total of 396 (73%) of patients chose the intravenous regimen, and 146 (27%) chose the oral route. They were permitted to switch treatment groups once during the study if they experienced adverse effects.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

In patients who chose the intravenous route of administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

So far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance; 15 went from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions. By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improvements in gastrointestinal tolerance compared with baseline.

“Patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance [seem to] prefer intravenous dosing, and patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki said. The study was sponsored by Roche Laboratories. Dr. Lewiecki made no disclosures.

TORONTO — Patients with osteoporosis who took daily raloxifene following a yearlong course of treatment with teriparatide maintained bone mineral density gains, whereas those who had no further therapy rapidly lost bone, Dr. Silvano Adami reported at a world congress on osteoporosis.

Recombinant teriparatide (human parathyroid hormone 1–34) treatment increases bone mass and reduces fracture risk by stimulating bone formation and remodeling, but there are concerns about its long-term safety. The Fracture Prevention Trial was terminated early in 1998 because of the occurrence of osteosarcomas in rats, and although no sarcomas developed in patients in the study, the drug subsequently was not recommended for use for any longer than 2 years.

Clinical experience has shown, however, that once therapy with teriparatide ceases, the bone mineral density (BMD) gains achieved during treatment quickly diminish. Therefore, subsequent antiresorptive therapy has been suggested as a means of maintaining the improvements.

Results of a new study support this concept of sequential therapy, said Dr. Adami of the University of Verona, Italy.

The study included 380 postmenopausal women who had completed 1 year of open-label treatment with 20 mcg/day of teriparatide. They were randomized to an additional year of raloxifene (60 mg/day) or placebo and were followed with dual-energy X-ray absorptiometry.

One year of teriparatide significantly increased BMD at the lumbar spine and femoral neck, by 8.2% and 1.3%, respectively, Dr. Adami said at the meeting, which was sponsored by the International Osteoporosis Foundation. At the end of the second year, patients who had received raloxifene showed a further significant increase in femoral neck BMD of 2.3%. (See chart.)

Correlations also were seen between the changes in bone markers and BMD during the first 3 months after raloxifene therapy, he said.

The sequential approach to therapy is not the first combination strategy to be evaluated for teriparatide. An earlier hypothesis had been that concurrent administration of an antiresorptive drug with parathyroid hormone (PTH) might enhance teriparatide's anabolic effects.

This hypothesis was tested in two studies in which parathyroid hormones were given in combination with alendronate. In one of the studies, 238 postmenopausal women with low BMD were randomized to receive daily parathyroid hormone (100 mcg), alendronate (10 mg), or both for 12 months. The investigators found no evidence of synergy for the combination therapy, reporting that the increase in volumetric density of spinal trabecular bone in the parathyroid hormone group was about double that seen in the other groups. They suggested the concurrent use of alendronate might be attenuating the anabolic effects of teriparatide (N. Engl. J. Med. 2003;349:1207–15).

In the second study, 83 men who had low BMD were randomized to receive parathyroid hormone (40 mcg daily), alendronate (10 mg daily), or both. This study also showed no benefit, with BMD at the femoral neck increasing significantly more in those men who received the parathyroid hormone alone than it did in those who were in the alendronate or combination groups (N. Engl. J. Med. 2003;349:1216–26).

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — Patients with osteoporosis who took daily raloxifene following a yearlong course of treatment with teriparatide maintained bone mineral density gains, whereas those who had no further therapy rapidly lost bone, Dr. Silvano Adami reported at a world congress on osteoporosis.

Recombinant teriparatide (human parathyroid hormone 1–34) treatment increases bone mass and reduces fracture risk by stimulating bone formation and remodeling, but there are concerns about its long-term safety. The Fracture Prevention Trial was terminated early in 1998 because of the occurrence of osteosarcomas in rats, and although no sarcomas developed in patients in the study, the drug subsequently was not recommended for use for any longer than 2 years.

Clinical experience has shown, however, that once therapy with teriparatide ceases, the bone mineral density (BMD) gains achieved during treatment quickly diminish. Therefore, subsequent antiresorptive therapy has been suggested as a means of maintaining the improvements.

Results of a new study support this concept of sequential therapy, said Dr. Adami of the University of Verona, Italy.

The study included 380 postmenopausal women who had completed 1 year of open-label treatment with 20 mcg/day of teriparatide. They were randomized to an additional year of raloxifene (60 mg/day) or placebo and were followed with dual-energy X-ray absorptiometry.

One year of teriparatide significantly increased BMD at the lumbar spine and femoral neck, by 8.2% and 1.3%, respectively, Dr. Adami said at the meeting, which was sponsored by the International Osteoporosis Foundation. At the end of the second year, patients who had received raloxifene showed a further significant increase in femoral neck BMD of 2.3%. (See chart.)

Correlations also were seen between the changes in bone markers and BMD during the first 3 months after raloxifene therapy, he said.

The sequential approach to therapy is not the first combination strategy to be evaluated for teriparatide. An earlier hypothesis had been that concurrent administration of an antiresorptive drug with parathyroid hormone (PTH) might enhance teriparatide's anabolic effects.

This hypothesis was tested in two studies in which parathyroid hormones were given in combination with alendronate. In one of the studies, 238 postmenopausal women with low BMD were randomized to receive daily parathyroid hormone (100 mcg), alendronate (10 mg), or both for 12 months. The investigators found no evidence of synergy for the combination therapy, reporting that the increase in volumetric density of spinal trabecular bone in the parathyroid hormone group was about double that seen in the other groups. They suggested the concurrent use of alendronate might be attenuating the anabolic effects of teriparatide (N. Engl. J. Med. 2003;349:1207–15).

In the second study, 83 men who had low BMD were randomized to receive parathyroid hormone (40 mcg daily), alendronate (10 mg daily), or both. This study also showed no benefit, with BMD at the femoral neck increasing significantly more in those men who received the parathyroid hormone alone than it did in those who were in the alendronate or combination groups (N. Engl. J. Med. 2003;349:1216–26).

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — Patients with osteoporosis who took daily raloxifene following a yearlong course of treatment with teriparatide maintained bone mineral density gains, whereas those who had no further therapy rapidly lost bone, Dr. Silvano Adami reported at a world congress on osteoporosis.

Recombinant teriparatide (human parathyroid hormone 1–34) treatment increases bone mass and reduces fracture risk by stimulating bone formation and remodeling, but there are concerns about its long-term safety. The Fracture Prevention Trial was terminated early in 1998 because of the occurrence of osteosarcomas in rats, and although no sarcomas developed in patients in the study, the drug subsequently was not recommended for use for any longer than 2 years.

Clinical experience has shown, however, that once therapy with teriparatide ceases, the bone mineral density (BMD) gains achieved during treatment quickly diminish. Therefore, subsequent antiresorptive therapy has been suggested as a means of maintaining the improvements.

Results of a new study support this concept of sequential therapy, said Dr. Adami of the University of Verona, Italy.

The study included 380 postmenopausal women who had completed 1 year of open-label treatment with 20 mcg/day of teriparatide. They were randomized to an additional year of raloxifene (60 mg/day) or placebo and were followed with dual-energy X-ray absorptiometry.

One year of teriparatide significantly increased BMD at the lumbar spine and femoral neck, by 8.2% and 1.3%, respectively, Dr. Adami said at the meeting, which was sponsored by the International Osteoporosis Foundation. At the end of the second year, patients who had received raloxifene showed a further significant increase in femoral neck BMD of 2.3%. (See chart.)

Correlations also were seen between the changes in bone markers and BMD during the first 3 months after raloxifene therapy, he said.

The sequential approach to therapy is not the first combination strategy to be evaluated for teriparatide. An earlier hypothesis had been that concurrent administration of an antiresorptive drug with parathyroid hormone (PTH) might enhance teriparatide's anabolic effects.

This hypothesis was tested in two studies in which parathyroid hormones were given in combination with alendronate. In one of the studies, 238 postmenopausal women with low BMD were randomized to receive daily parathyroid hormone (100 mcg), alendronate (10 mg), or both for 12 months. The investigators found no evidence of synergy for the combination therapy, reporting that the increase in volumetric density of spinal trabecular bone in the parathyroid hormone group was about double that seen in the other groups. They suggested the concurrent use of alendronate might be attenuating the anabolic effects of teriparatide (N. Engl. J. Med. 2003;349:1207–15).

In the second study, 83 men who had low BMD were randomized to receive parathyroid hormone (40 mcg daily), alendronate (10 mg daily), or both. This study also showed no benefit, with BMD at the femoral neck increasing significantly more in those men who received the parathyroid hormone alone than it did in those who were in the alendronate or combination groups (N. Engl. J. Med. 2003;349:1216–26).

ELSEVIER GLOBAL MEDICAL NEWS

NEW YORK – Traumatic stress in youth is the single most important contributor to later psychiatric morbidity and mortality, and the American Psychiatric Association should make violence and its sequelae a major organizational priority, according to a new report.

The report of the APA Task Force on the Biopsychosocial Consequences of Childhood Violence, which is being submitted by the association's Joint Reference Committee for approval, also concluded that the prevention of trauma and violence is potentially the single most effective strategy for the prevention of mental illness.

Much of the epidemiologic data on exposure to violence during childhood has emerged from the Adverse Childhood Experiences (ACE) study, which is a collaboration of the Centers for Disease Control and Prevention and the Kaiser-Permanente Medical Care Program in San Diego. This ongoing study, which is investigating the impact of adverse childhood experiences on adult health, includes approximately 175,000 members of the Kaiser health plan, co-principal investigator Vincent J. Felitti said at the American Psychiatric Association's Institute on Psychiatric Services.

The ACE study has identified several specific categories of adverse childhood experiences that are associated with numerous health risk factors later in life, and has found these experiences to be far more common than was previously appreciated. (See box at right.)

The subjects in the study are predominantly white and well educated. “In no way can this group be considered an aberrant population,” said Dr. Felitti, who is an internist with Kaiser-Permanente and clinical professor of medicine, University of California, San Diego.

Nonetheless, more than half reported having experienced at least one of these early life adverse events (ACE score one) and one-quarter reported having two or more, according to Dr. Felitti. Serious physical and emotional abuse was reported by one in nine people, and sexual abuse was reported by 28% of women and 16% of men. “This is hard to believe unless you routinely ask people–in which case it becomes blatantly obvious,” he said.

Then the ACE researchers looked at the impact of these events on health risk factors in adulthood. Smoking and self-acknowledged alcohol abuse strongly correlated with childhood exposure to violence, as did intravenous drug use. For males who had an ACE score of six or higher, there was a 46-fold increase in likelihood of intravenous drug use. An ACE score of six or higher also was associated with a 30- to 51-fold increase in the likelihood of attempted suicide in later life, he said.

The report also highlights the fact that traumatic stress is not only linked to psychological disorders such as depression and posttraumatic stress disorder (PTSD), but is also a major etiologic factor in medical morbidity and mortality. For example, regular smoking before age 14 not only correlated with early life exposure to violence, but also with later development of chronic obstructive pulmonary disease. “This was an important conceptual shift, the conversion of life experience into biomedical disease,” Dr. Felitti said. And this conversion extended to ischemic heart disease, cancer, fractures, and liver disease.

Nonetheless, although exposure to violence heightens the risk for the development of PTSD, other stress-related disorders, and medical morbidity, it is not necessarily predictive of psychopathology. Another task force member, Dr. Carl C. Bell, who is chief executive officer of Community Mental Health Council Inc. in Chicago, emphasized this point. “Risk factors are not predictive factors because of protective factors,” he said. Only one-third of individuals exposed to violence develop PTSD. The rest are characterized by a variety of protective factors, such as intellectual ability, a feeling of connectedness, and having an internal locus of control and blame, according to Dr. Bell, who is also clinical professor of psychiatry and public health, University of Illinois in Chicago.

These protective factors together cultivate resilience and stress resistance in the individual, and psychiatrists have an important role in helping individuals cultivate resiliency by means of a community psychiatry model, the task force report states. (See box at left.)

The APA can play a major role in improving the lives of children and preventing psychiatric disorders. “With the external environment that we find ourselves in today, with a war going on, school shootings, and what's been going on between a member of Congress and some pages, we have violence and trauma all around us,” said another task force member, William W. Harris, Ph.D.

“But we just say 'isn't that horrible?' and then we move on. There's a collective denial,” said Dr. Harris, president of KidsPac, a political action committee dedicated to obtaining federal government assistance for disadvantaged children.

The APA's willingness to take on the profound issues associated with violence, however, is hopeful, Dr. Harris said. The task force recommended that the APA make a long-term commitment to addressing issues of trauma, establishing a committee with a 5-year mandate to raise consciousness within psychiatry, and to address fiscal issues, training, research, prevention, and public education.

“The only way this is going to happen politically is to form many partnerships, both within the APA and other professional organizations, the police, Head Start, and early childhood care teachers, so they begin to understand more about these kids,” he said. The APA's formation of this committee will be an important first step, he said.

ELSEVIER GLOBAL MEDICAL NEWS

Cultivating Resiliency

Seven strategies that psychiatrists can employ to encourage wellness and resiliency are:

Reestablishing “the village,” providing a sense of community connection and life.

Providing access to health care.

Improving bonding, attachment, and connectedness dynamics that in turn facilitate “collective efficacy.”

Improving self-esteem.

Increasing the individual's social skills.

Reestablishing the adult protective shield and monitoring problem behaviors.

Minimizing the residual effects of trauma.

Source: Report of the APA Task Force on the Biopsychosocial Consequences of Childhood Violence

NEW YORK – Traumatic stress in youth is the single most important contributor to later psychiatric morbidity and mortality, and the American Psychiatric Association should make violence and its sequelae a major organizational priority, according to a new report.

The report of the APA Task Force on the Biopsychosocial Consequences of Childhood Violence, which is being submitted by the association's Joint Reference Committee for approval, also concluded that the prevention of trauma and violence is potentially the single most effective strategy for the prevention of mental illness.

Much of the epidemiologic data on exposure to violence during childhood has emerged from the Adverse Childhood Experiences (ACE) study, which is a collaboration of the Centers for Disease Control and Prevention and the Kaiser-Permanente Medical Care Program in San Diego. This ongoing study, which is investigating the impact of adverse childhood experiences on adult health, includes approximately 175,000 members of the Kaiser health plan, co-principal investigator Vincent J. Felitti said at the American Psychiatric Association's Institute on Psychiatric Services.

The ACE study has identified several specific categories of adverse childhood experiences that are associated with numerous health risk factors later in life, and has found these experiences to be far more common than was previously appreciated. (See box at right.)

The subjects in the study are predominantly white and well educated. “In no way can this group be considered an aberrant population,” said Dr. Felitti, who is an internist with Kaiser-Permanente and clinical professor of medicine, University of California, San Diego.

Nonetheless, more than half reported having experienced at least one of these early life adverse events (ACE score one) and one-quarter reported having two or more, according to Dr. Felitti. Serious physical and emotional abuse was reported by one in nine people, and sexual abuse was reported by 28% of women and 16% of men. “This is hard to believe unless you routinely ask people–in which case it becomes blatantly obvious,” he said.

Then the ACE researchers looked at the impact of these events on health risk factors in adulthood. Smoking and self-acknowledged alcohol abuse strongly correlated with childhood exposure to violence, as did intravenous drug use. For males who had an ACE score of six or higher, there was a 46-fold increase in likelihood of intravenous drug use. An ACE score of six or higher also was associated with a 30- to 51-fold increase in the likelihood of attempted suicide in later life, he said.

The report also highlights the fact that traumatic stress is not only linked to psychological disorders such as depression and posttraumatic stress disorder (PTSD), but is also a major etiologic factor in medical morbidity and mortality. For example, regular smoking before age 14 not only correlated with early life exposure to violence, but also with later development of chronic obstructive pulmonary disease. “This was an important conceptual shift, the conversion of life experience into biomedical disease,” Dr. Felitti said. And this conversion extended to ischemic heart disease, cancer, fractures, and liver disease.

Nonetheless, although exposure to violence heightens the risk for the development of PTSD, other stress-related disorders, and medical morbidity, it is not necessarily predictive of psychopathology. Another task force member, Dr. Carl C. Bell, who is chief executive officer of Community Mental Health Council Inc. in Chicago, emphasized this point. “Risk factors are not predictive factors because of protective factors,” he said. Only one-third of individuals exposed to violence develop PTSD. The rest are characterized by a variety of protective factors, such as intellectual ability, a feeling of connectedness, and having an internal locus of control and blame, according to Dr. Bell, who is also clinical professor of psychiatry and public health, University of Illinois in Chicago.

These protective factors together cultivate resilience and stress resistance in the individual, and psychiatrists have an important role in helping individuals cultivate resiliency by means of a community psychiatry model, the task force report states. (See box at left.)

The APA can play a major role in improving the lives of children and preventing psychiatric disorders. “With the external environment that we find ourselves in today, with a war going on, school shootings, and what's been going on between a member of Congress and some pages, we have violence and trauma all around us,” said another task force member, William W. Harris, Ph.D.

“But we just say 'isn't that horrible?' and then we move on. There's a collective denial,” said Dr. Harris, president of KidsPac, a political action committee dedicated to obtaining federal government assistance for disadvantaged children.

The APA's willingness to take on the profound issues associated with violence, however, is hopeful, Dr. Harris said. The task force recommended that the APA make a long-term commitment to addressing issues of trauma, establishing a committee with a 5-year mandate to raise consciousness within psychiatry, and to address fiscal issues, training, research, prevention, and public education.

“The only way this is going to happen politically is to form many partnerships, both within the APA and other professional organizations, the police, Head Start, and early childhood care teachers, so they begin to understand more about these kids,” he said. The APA's formation of this committee will be an important first step, he said.

ELSEVIER GLOBAL MEDICAL NEWS

Cultivating Resiliency

Seven strategies that psychiatrists can employ to encourage wellness and resiliency are:

Reestablishing “the village,” providing a sense of community connection and life.

Providing access to health care.

Improving bonding, attachment, and connectedness dynamics that in turn facilitate “collective efficacy.”

Improving self-esteem.

Increasing the individual's social skills.

Reestablishing the adult protective shield and monitoring problem behaviors.

Minimizing the residual effects of trauma.

Source: Report of the APA Task Force on the Biopsychosocial Consequences of Childhood Violence

NEW YORK – Traumatic stress in youth is the single most important contributor to later psychiatric morbidity and mortality, and the American Psychiatric Association should make violence and its sequelae a major organizational priority, according to a new report.

The report of the APA Task Force on the Biopsychosocial Consequences of Childhood Violence, which is being submitted by the association's Joint Reference Committee for approval, also concluded that the prevention of trauma and violence is potentially the single most effective strategy for the prevention of mental illness.

Much of the epidemiologic data on exposure to violence during childhood has emerged from the Adverse Childhood Experiences (ACE) study, which is a collaboration of the Centers for Disease Control and Prevention and the Kaiser-Permanente Medical Care Program in San Diego. This ongoing study, which is investigating the impact of adverse childhood experiences on adult health, includes approximately 175,000 members of the Kaiser health plan, co-principal investigator Vincent J. Felitti said at the American Psychiatric Association's Institute on Psychiatric Services.

The ACE study has identified several specific categories of adverse childhood experiences that are associated with numerous health risk factors later in life, and has found these experiences to be far more common than was previously appreciated. (See box at right.)

The subjects in the study are predominantly white and well educated. “In no way can this group be considered an aberrant population,” said Dr. Felitti, who is an internist with Kaiser-Permanente and clinical professor of medicine, University of California, San Diego.

Nonetheless, more than half reported having experienced at least one of these early life adverse events (ACE score one) and one-quarter reported having two or more, according to Dr. Felitti. Serious physical and emotional abuse was reported by one in nine people, and sexual abuse was reported by 28% of women and 16% of men. “This is hard to believe unless you routinely ask people–in which case it becomes blatantly obvious,” he said.

Then the ACE researchers looked at the impact of these events on health risk factors in adulthood. Smoking and self-acknowledged alcohol abuse strongly correlated with childhood exposure to violence, as did intravenous drug use. For males who had an ACE score of six or higher, there was a 46-fold increase in likelihood of intravenous drug use. An ACE score of six or higher also was associated with a 30- to 51-fold increase in the likelihood of attempted suicide in later life, he said.

The report also highlights the fact that traumatic stress is not only linked to psychological disorders such as depression and posttraumatic stress disorder (PTSD), but is also a major etiologic factor in medical morbidity and mortality. For example, regular smoking before age 14 not only correlated with early life exposure to violence, but also with later development of chronic obstructive pulmonary disease. “This was an important conceptual shift, the conversion of life experience into biomedical disease,” Dr. Felitti said. And this conversion extended to ischemic heart disease, cancer, fractures, and liver disease.

Nonetheless, although exposure to violence heightens the risk for the development of PTSD, other stress-related disorders, and medical morbidity, it is not necessarily predictive of psychopathology. Another task force member, Dr. Carl C. Bell, who is chief executive officer of Community Mental Health Council Inc. in Chicago, emphasized this point. “Risk factors are not predictive factors because of protective factors,” he said. Only one-third of individuals exposed to violence develop PTSD. The rest are characterized by a variety of protective factors, such as intellectual ability, a feeling of connectedness, and having an internal locus of control and blame, according to Dr. Bell, who is also clinical professor of psychiatry and public health, University of Illinois in Chicago.

These protective factors together cultivate resilience and stress resistance in the individual, and psychiatrists have an important role in helping individuals cultivate resiliency by means of a community psychiatry model, the task force report states. (See box at left.)

The APA can play a major role in improving the lives of children and preventing psychiatric disorders. “With the external environment that we find ourselves in today, with a war going on, school shootings, and what's been going on between a member of Congress and some pages, we have violence and trauma all around us,” said another task force member, William W. Harris, Ph.D.

“But we just say 'isn't that horrible?' and then we move on. There's a collective denial,” said Dr. Harris, president of KidsPac, a political action committee dedicated to obtaining federal government assistance for disadvantaged children.

The APA's willingness to take on the profound issues associated with violence, however, is hopeful, Dr. Harris said. The task force recommended that the APA make a long-term commitment to addressing issues of trauma, establishing a committee with a 5-year mandate to raise consciousness within psychiatry, and to address fiscal issues, training, research, prevention, and public education.

“The only way this is going to happen politically is to form many partnerships, both within the APA and other professional organizations, the police, Head Start, and early childhood care teachers, so they begin to understand more about these kids,” he said. The APA's formation of this committee will be an important first step, he said.

ELSEVIER GLOBAL MEDICAL NEWS

Cultivating Resiliency

Seven strategies that psychiatrists can employ to encourage wellness and resiliency are:

Reestablishing “the village,” providing a sense of community connection and life.

Providing access to health care.

Improving bonding, attachment, and connectedness dynamics that in turn facilitate “collective efficacy.”

Improving self-esteem.

Increasing the individual's social skills.

Reestablishing the adult protective shield and monitoring problem behaviors.

Minimizing the residual effects of trauma.

Source: Report of the APA Task Force on the Biopsychosocial Consequences of Childhood Violence

TORONTO — For the first time, the microarchitecture of cortical and trabecular bone can be visualized noninvasively using a high-resolution CT scanner, Dr. Pierre D. Delmas reported at a world congress on osteoporosis.

Measurement of bone density by dual-energy x-ray absorptiometry (DXA) captures only part of the fracture risk in postmenopausal women, Dr. Delmas said. Treatment decisions based on DXA alone can miss a large proportion of women who may have fractures later.

This development may ultimately permit a fuller understanding of the mechanisms involved in osteoporosis and provide more accurate fracture risk assessment and disease monitoring capability, he said.

The device, a 3-D peripheral quantitative computed tomography (pQCT) scanner (XtremeCT, Scanco Medical AG, Bassersdorf, Switzerland), has greater resolution than conventional CT scanners, and permits visualization of trabecular number, thickness, and separation, as well as cortical thickness, said Dr. Delmas, professor of medicine, Claude Bernard University in Lyon, France.

As an example of the capability of this device, he described a case-control study that included 57 women who had experienced fragility fractures during 13 years of follow-up and were evaluated with pQCT. “We found that for every standard deviation decrease in total and trabecular density, and cortical and trabecular thickness, there was a significant increase in risk of fracture,” he said. Moreover, the increases remained significant after adjusting for bone mineral density (BMD) as measured by DXA, suggesting that the two approaches are independent measurements of bone strength, said Dr. Delmas, who is president of the International Osteoporosis Foundation, the sponsor of the meeting. A further capability of the high-resolution pQCT device is that, unlike DXA, it can reveal localized abnormalities in bone structure, he said.

During a press briefing at the meeting Dr. Delmas was asked who might be an appropriate candidate for this type of evaluation. “We need to show in prospective studies that we can do better than with DXA. If we do so you could argue that any postmenopausal woman who is at risk of fracture should have the test, but it's too early to say,” he replied.

He also commented that he and his colleagues plan to conduct studies using pQCT to measure the efficacy of therapy, and to gain insight into how antiosteoporosis drug therapy works. “The paradox is that we have a variety of drugs that are useful in decreasing the risk of fracture, but we're not always sure what is really causing the improved bone strength,” he said. Changes in bone among premenopausal women, important for the overall understanding of skeletal fragility, also are being investigated.

In another presentation at the meeting, Dr. Stephanie Boutroy described a cross-sectional study that included 235 women aged 19–50 years who underwent a scan at the distal radius and tibia with the high-resolution device.

Among the age-related changes seen were small increases in the radius and tibia cross-sectional areas without a correlating change in cortical thickness. “This reflects periosteal apposition and endosteal resorption of similar magnitude,” explained Dr. Boutroy, also of Claude Bernard University. No correlation was seen in density and architecture parameters with age at the radius, but at the tibia there was an age-related 17% decrease in trabecular density, she said. This was explained by a decrease in trabecular number, separation, and distribution.

Age-related changes in bone architecture had been noted previously in another study by Dr. Boutroy and her colleagues that included 108 premenopausal and 148 postmenopausal women. Lumbar spine and femoral neck BMD were measured using DXA; volumetric BMD and microarchitecture were measured at the distal radius and tibia using high-resolution pQCT.

By using the high-resolution device, they were able to detect significant changes in trabecular density, number, and thickness, as well as in cortical thickness. They also found that, unlike with DXA, they were able to discriminate between women with osteopenia who had had a previous fracture and those who had not (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

The cost of the device is currently high, noted Dr. Delmas, at approximately $300,000, and there are only about 15 in use around the world. “But I expect that if our technique is validated by other studies and the device is produced on a larger scale the price will come down,” he said, adding that he has no financial interest in the company.

Shown are a 3-D peripheral quantitative CT scan of a tibia in a healthy woman (left) and a 3-D pQCT scan of a tibia in an osteoporotic woman (right). Photos courtesy Dr. Stephanie Boutroy

TORONTO — For the first time, the microarchitecture of cortical and trabecular bone can be visualized noninvasively using a high-resolution CT scanner, Dr. Pierre D. Delmas reported at a world congress on osteoporosis.

Measurement of bone density by dual-energy x-ray absorptiometry (DXA) captures only part of the fracture risk in postmenopausal women, Dr. Delmas said. Treatment decisions based on DXA alone can miss a large proportion of women who may have fractures later.

This development may ultimately permit a fuller understanding of the mechanisms involved in osteoporosis and provide more accurate fracture risk assessment and disease monitoring capability, he said.

The device, a 3-D peripheral quantitative computed tomography (pQCT) scanner (XtremeCT, Scanco Medical AG, Bassersdorf, Switzerland), has greater resolution than conventional CT scanners, and permits visualization of trabecular number, thickness, and separation, as well as cortical thickness, said Dr. Delmas, professor of medicine, Claude Bernard University in Lyon, France.

As an example of the capability of this device, he described a case-control study that included 57 women who had experienced fragility fractures during 13 years of follow-up and were evaluated with pQCT. “We found that for every standard deviation decrease in total and trabecular density, and cortical and trabecular thickness, there was a significant increase in risk of fracture,” he said. Moreover, the increases remained significant after adjusting for bone mineral density (BMD) as measured by DXA, suggesting that the two approaches are independent measurements of bone strength, said Dr. Delmas, who is president of the International Osteoporosis Foundation, the sponsor of the meeting. A further capability of the high-resolution pQCT device is that, unlike DXA, it can reveal localized abnormalities in bone structure, he said.

During a press briefing at the meeting Dr. Delmas was asked who might be an appropriate candidate for this type of evaluation. “We need to show in prospective studies that we can do better than with DXA. If we do so you could argue that any postmenopausal woman who is at risk of fracture should have the test, but it's too early to say,” he replied.

He also commented that he and his colleagues plan to conduct studies using pQCT to measure the efficacy of therapy, and to gain insight into how antiosteoporosis drug therapy works. “The paradox is that we have a variety of drugs that are useful in decreasing the risk of fracture, but we're not always sure what is really causing the improved bone strength,” he said. Changes in bone among premenopausal women, important for the overall understanding of skeletal fragility, also are being investigated.

In another presentation at the meeting, Dr. Stephanie Boutroy described a cross-sectional study that included 235 women aged 19–50 years who underwent a scan at the distal radius and tibia with the high-resolution device.

Among the age-related changes seen were small increases in the radius and tibia cross-sectional areas without a correlating change in cortical thickness. “This reflects periosteal apposition and endosteal resorption of similar magnitude,” explained Dr. Boutroy, also of Claude Bernard University. No correlation was seen in density and architecture parameters with age at the radius, but at the tibia there was an age-related 17% decrease in trabecular density, she said. This was explained by a decrease in trabecular number, separation, and distribution.

Age-related changes in bone architecture had been noted previously in another study by Dr. Boutroy and her colleagues that included 108 premenopausal and 148 postmenopausal women. Lumbar spine and femoral neck BMD were measured using DXA; volumetric BMD and microarchitecture were measured at the distal radius and tibia using high-resolution pQCT.

By using the high-resolution device, they were able to detect significant changes in trabecular density, number, and thickness, as well as in cortical thickness. They also found that, unlike with DXA, they were able to discriminate between women with osteopenia who had had a previous fracture and those who had not (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

The cost of the device is currently high, noted Dr. Delmas, at approximately $300,000, and there are only about 15 in use around the world. “But I expect that if our technique is validated by other studies and the device is produced on a larger scale the price will come down,” he said, adding that he has no financial interest in the company.

Shown are a 3-D peripheral quantitative CT scan of a tibia in a healthy woman (left) and a 3-D pQCT scan of a tibia in an osteoporotic woman (right). Photos courtesy Dr. Stephanie Boutroy

TORONTO — For the first time, the microarchitecture of cortical and trabecular bone can be visualized noninvasively using a high-resolution CT scanner, Dr. Pierre D. Delmas reported at a world congress on osteoporosis.

Measurement of bone density by dual-energy x-ray absorptiometry (DXA) captures only part of the fracture risk in postmenopausal women, Dr. Delmas said. Treatment decisions based on DXA alone can miss a large proportion of women who may have fractures later.

This development may ultimately permit a fuller understanding of the mechanisms involved in osteoporosis and provide more accurate fracture risk assessment and disease monitoring capability, he said.

The device, a 3-D peripheral quantitative computed tomography (pQCT) scanner (XtremeCT, Scanco Medical AG, Bassersdorf, Switzerland), has greater resolution than conventional CT scanners, and permits visualization of trabecular number, thickness, and separation, as well as cortical thickness, said Dr. Delmas, professor of medicine, Claude Bernard University in Lyon, France.

As an example of the capability of this device, he described a case-control study that included 57 women who had experienced fragility fractures during 13 years of follow-up and were evaluated with pQCT. “We found that for every standard deviation decrease in total and trabecular density, and cortical and trabecular thickness, there was a significant increase in risk of fracture,” he said. Moreover, the increases remained significant after adjusting for bone mineral density (BMD) as measured by DXA, suggesting that the two approaches are independent measurements of bone strength, said Dr. Delmas, who is president of the International Osteoporosis Foundation, the sponsor of the meeting. A further capability of the high-resolution pQCT device is that, unlike DXA, it can reveal localized abnormalities in bone structure, he said.

During a press briefing at the meeting Dr. Delmas was asked who might be an appropriate candidate for this type of evaluation. “We need to show in prospective studies that we can do better than with DXA. If we do so you could argue that any postmenopausal woman who is at risk of fracture should have the test, but it's too early to say,” he replied.

He also commented that he and his colleagues plan to conduct studies using pQCT to measure the efficacy of therapy, and to gain insight into how antiosteoporosis drug therapy works. “The paradox is that we have a variety of drugs that are useful in decreasing the risk of fracture, but we're not always sure what is really causing the improved bone strength,” he said. Changes in bone among premenopausal women, important for the overall understanding of skeletal fragility, also are being investigated.

In another presentation at the meeting, Dr. Stephanie Boutroy described a cross-sectional study that included 235 women aged 19–50 years who underwent a scan at the distal radius and tibia with the high-resolution device.

Among the age-related changes seen were small increases in the radius and tibia cross-sectional areas without a correlating change in cortical thickness. “This reflects periosteal apposition and endosteal resorption of similar magnitude,” explained Dr. Boutroy, also of Claude Bernard University. No correlation was seen in density and architecture parameters with age at the radius, but at the tibia there was an age-related 17% decrease in trabecular density, she said. This was explained by a decrease in trabecular number, separation, and distribution.

Age-related changes in bone architecture had been noted previously in another study by Dr. Boutroy and her colleagues that included 108 premenopausal and 148 postmenopausal women. Lumbar spine and femoral neck BMD were measured using DXA; volumetric BMD and microarchitecture were measured at the distal radius and tibia using high-resolution pQCT.

By using the high-resolution device, they were able to detect significant changes in trabecular density, number, and thickness, as well as in cortical thickness. They also found that, unlike with DXA, they were able to discriminate between women with osteopenia who had had a previous fracture and those who had not (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

The cost of the device is currently high, noted Dr. Delmas, at approximately $300,000, and there are only about 15 in use around the world. “But I expect that if our technique is validated by other studies and the device is produced on a larger scale the price will come down,” he said, adding that he has no financial interest in the company.

Shown are a 3-D peripheral quantitative CT scan of a tibia in a healthy woman (left) and a 3-D pQCT scan of a tibia in an osteoporotic woman (right). Photos courtesy Dr. Stephanie Boutroy