Diana Mahoney

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

“Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk,” Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781–6).

Further, Merck's marketing strategy included awarding “sizeable educational grants” to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. “We did not require any reporting or review of any materials developed,” Ms. Eisele said. “Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences.”

“We value our relationships with these groups and [strictly adhere] to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals,” she said. In addition, “Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education.”

Dr. Rothman and Dr. Rothman said that the role of several professional medical associations in the marketing of the HPV vaccine “is cause for concern.”

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said.

Given the potential for conflicts of interest associated with an industry-supported educational program, “we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently,” said Dr. L. Stewart Massad, chair of ASCCP's Practice and Ethics committees, noting that he accepts no financial support or grant money.

The American College of Obstetricians and Gynecologists (ACOG) also received grant money for HPV vaccine education.

In an interview, Dr. Hal C. Lawrence III, vice president of practice activities for ACOG, emphasized that the college “thoroughly reviewed the evidence before making any recommendations about the HPV vaccine.”

“We wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine, both in the prevention of cervical cancer but also in other HPV illnesses,” he said.

Dr. Rothman and Dr. Rothman concluded that professional medical associations should refrain from promoting product-specific speakers bureaus and refuse funding that requires reporting activity to the donor. Neither reported having relevant financial disclosures.

ACOG 'wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine.'

Source DR. LAWRENCE

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

“Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk,” Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781–6).

Further, Merck's marketing strategy included awarding “sizeable educational grants” to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. “We did not require any reporting or review of any materials developed,” Ms. Eisele said. “Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences.”

“We value our relationships with these groups and [strictly adhere] to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals,” she said. In addition, “Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education.”

Dr. Rothman and Dr. Rothman said that the role of several professional medical associations in the marketing of the HPV vaccine “is cause for concern.”

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said.

Given the potential for conflicts of interest associated with an industry-supported educational program, “we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently,” said Dr. L. Stewart Massad, chair of ASCCP's Practice and Ethics committees, noting that he accepts no financial support or grant money.

The American College of Obstetricians and Gynecologists (ACOG) also received grant money for HPV vaccine education.

In an interview, Dr. Hal C. Lawrence III, vice president of practice activities for ACOG, emphasized that the college “thoroughly reviewed the evidence before making any recommendations about the HPV vaccine.”

“We wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine, both in the prevention of cervical cancer but also in other HPV illnesses,” he said.

Dr. Rothman and Dr. Rothman concluded that professional medical associations should refrain from promoting product-specific speakers bureaus and refuse funding that requires reporting activity to the donor. Neither reported having relevant financial disclosures.

ACOG 'wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine.'

Source DR. LAWRENCE

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

“Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk,” Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781–6).

Further, Merck's marketing strategy included awarding “sizeable educational grants” to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. “We did not require any reporting or review of any materials developed,” Ms. Eisele said. “Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences.”

“We value our relationships with these groups and [strictly adhere] to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals,” she said. In addition, “Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education.”

Dr. Rothman and Dr. Rothman said that the role of several professional medical associations in the marketing of the HPV vaccine “is cause for concern.”

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said.

Given the potential for conflicts of interest associated with an industry-supported educational program, “we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently,” said Dr. L. Stewart Massad, chair of ASCCP's Practice and Ethics committees, noting that he accepts no financial support or grant money.

The American College of Obstetricians and Gynecologists (ACOG) also received grant money for HPV vaccine education.

In an interview, Dr. Hal C. Lawrence III, vice president of practice activities for ACOG, emphasized that the college “thoroughly reviewed the evidence before making any recommendations about the HPV vaccine.”

“We wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine, both in the prevention of cervical cancer but also in other HPV illnesses,” he said.

Dr. Rothman and Dr. Rothman concluded that professional medical associations should refrain from promoting product-specific speakers bureaus and refuse funding that requires reporting activity to the donor. Neither reported having relevant financial disclosures.

ACOG 'wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine.'

Source DR. LAWRENCE

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although most nail unit lesions are benign, “malignancies are not as obvious to spot clinically as you would think,” and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed. Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix), as a nodule or tumor with or without nail loss, as a wartlike periungual lesion with nail splitting and skin fissure, or as a draining subungual mass. Because these presentations mimic other clinical entities, “you have to biopsy to get an accurate diagnosis.”

For the aforementioned lesions, “you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs,” Dr. Rich said.

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, Dr. Rich said. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin-deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign), if there is variability in the pigmentation of the band, if the pigmented band is widening or growing, or if there is bleeding or signs of ulceration, Dr. Rich explained.

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, Dr. Rich said. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, “unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation,” Dr. Rich said. “In that case, a full thickness biopsy is needed.”

For large lesions located in the lateral third of the nail, she added, “a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium.”

Patients are typically apprehensive about nail surgery, so the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, she noted.

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma, which arises from the nail matrix, often presents initially as longitudinal melanonychia.

Source ©dermnet.com

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although most nail unit lesions are benign, “malignancies are not as obvious to spot clinically as you would think,” and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed. Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix), as a nodule or tumor with or without nail loss, as a wartlike periungual lesion with nail splitting and skin fissure, or as a draining subungual mass. Because these presentations mimic other clinical entities, “you have to biopsy to get an accurate diagnosis.”

For the aforementioned lesions, “you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs,” Dr. Rich said.

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, Dr. Rich said. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin-deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign), if there is variability in the pigmentation of the band, if the pigmented band is widening or growing, or if there is bleeding or signs of ulceration, Dr. Rich explained.

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, Dr. Rich said. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, “unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation,” Dr. Rich said. “In that case, a full thickness biopsy is needed.”

For large lesions located in the lateral third of the nail, she added, “a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium.”

Patients are typically apprehensive about nail surgery, so the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, she noted.

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma, which arises from the nail matrix, often presents initially as longitudinal melanonychia.

Source ©dermnet.com

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although most nail unit lesions are benign, “malignancies are not as obvious to spot clinically as you would think,” and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed. Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix), as a nodule or tumor with or without nail loss, as a wartlike periungual lesion with nail splitting and skin fissure, or as a draining subungual mass. Because these presentations mimic other clinical entities, “you have to biopsy to get an accurate diagnosis.”

For the aforementioned lesions, “you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs,” Dr. Rich said.

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, Dr. Rich said. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin-deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign), if there is variability in the pigmentation of the band, if the pigmented band is widening or growing, or if there is bleeding or signs of ulceration, Dr. Rich explained.

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, Dr. Rich said. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, “unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation,” Dr. Rich said. “In that case, a full thickness biopsy is needed.”

For large lesions located in the lateral third of the nail, she added, “a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium.”

Patients are typically apprehensive about nail surgery, so the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, she noted.

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma, which arises from the nail matrix, often presents initially as longitudinal melanonychia.

Source ©dermnet.com

A confident diagnosis of knee osteoarthritis can be made without radiographic examination in adults older than 40 years based on criteria described in evidence-based recommendations to be published by the European League Against Rheumatism.

The criteria include usage-related knee pain, short-lived morning stiffness, functional limitation, and one or more “typical” examination findings, such as crepitus, restricted movement, and bony enlargement.

Clinical signs, symptoms, risk factors, and plain radiography are the cornerstones of the recommendations, which have a focus on clinical diagnosis that distinguishes them from the American College of Rheumatology criteria, said Weiya Zhang, Ph.D., of the University of Nottingham (England). He is lead author of the recommendations, which were presented at the annual European Congress of Rheumatology in Copenhagen and are slated for publication in an upcoming issue of the Annals of Rheumatic Disease.

The recommendations were developed by a task force of 17 osteoarthritis experts from 12 European countries. A systematic literature search was undertaken to identify the best available evidence, which was combined with clinical expertise in gauging the strength of each recommendation. Diagnostic accuracy was tested using multiple predictive models in two populations, including one from the Netherlands and one from the United Kingdom, Dr. Zhang explained.

The risk factors found to be strongly associated with knee OA in patients with knee pain include age older than 50 years, female sex, high body mass index, previous knee injury or malalignment, joint laxity, occupational or recreational usage, family history, and the presence of Heberden's nodes, the task force concluded.

Although plain radiography of the knee (including a weight-bearing view, a semiflexed view, and lateral and skyline views) remains the standard imaging modality for morphologic assessment of knee OA, imaging is an adjunct for diagnostic purposes. Other imaging modalities, such as MRI, sonography, and scintigraphy, are “seldom indicated for diagnosis of OA,” according to the authors. Classic radiographic features “are focal joint space narrowing, osteophyte, subchondral bone sclerosis, and subchondral cysts.”

Other recommendations cover the definition of knee OA, subsets of the disease, typical symptoms and signs, the use of laboratory tests, and differential diagnosis:

▸ Knee OA is a common, complex joint disorder that is characterized clinically by usage-related pain and functional limitation. The disorder entails focal cartilage loss, new bone formation, and involvement of all joint tissues—changes that are mirrored radiographically.

▸ Subsets of knee OA are associated with different risk factors and outcomes, and can be defined by compartmental involvement, bone response, the global pattern of OA, crystal presence, and the degree of inflammation. However, “the ability to discriminate subsets and the relevance for routine practice are unclear,” the task force noted.

▸ The typical symptoms of knee OA are often episodic, variable in severity, and slow to change. Night pain and more persistent pain at rest may indicate advanced OA.

▸ In addition to the key findings indicative of knee OA (crepitus, restricted movement, and bony enlargement), additional features may include deformity, instability, periarticular or joint-line tenderness, and pain on patellofemoral compression.

▸ Such features as severe local inflammation, erythema, and progressive pain unrelated to usage should raise red flags, as they suggest sepsis, crystals, or serious bone pathology.

▸ Laboratory tests on blood, urine, or synovial fluid are not required for the diagnosis of knee OA, but they may be used to confirm or exclude other inflammatory conditions.

▸ Synovial fluid should be aspirated and analyzed if a palpable effusion is present, in order to confirm or exclude inflammatory disease and identify urate and calcium pyrophosphate crystals.

The authors acknowledged that the recommendations are limited because they were derived from literature based on different studies; the likelihood ratios pooled from the literature may be affected by multiple factors, including the number of studies, the populations considered, and the cutoff values selected; and there was no universally applicable reference standard for knee OA. Also, the recommendations could be different for “less typical” patients younger than age 40 years.

Dr. Zhang reported having no relevant financial relationships to disclose.

A confident diagnosis of knee osteoarthritis can be made without radiographic examination in adults older than 40 years based on criteria described in evidence-based recommendations to be published by the European League Against Rheumatism.

The criteria include usage-related knee pain, short-lived morning stiffness, functional limitation, and one or more “typical” examination findings, such as crepitus, restricted movement, and bony enlargement.

Clinical signs, symptoms, risk factors, and plain radiography are the cornerstones of the recommendations, which have a focus on clinical diagnosis that distinguishes them from the American College of Rheumatology criteria, said Weiya Zhang, Ph.D., of the University of Nottingham (England). He is lead author of the recommendations, which were presented at the annual European Congress of Rheumatology in Copenhagen and are slated for publication in an upcoming issue of the Annals of Rheumatic Disease.

The recommendations were developed by a task force of 17 osteoarthritis experts from 12 European countries. A systematic literature search was undertaken to identify the best available evidence, which was combined with clinical expertise in gauging the strength of each recommendation. Diagnostic accuracy was tested using multiple predictive models in two populations, including one from the Netherlands and one from the United Kingdom, Dr. Zhang explained.

The risk factors found to be strongly associated with knee OA in patients with knee pain include age older than 50 years, female sex, high body mass index, previous knee injury or malalignment, joint laxity, occupational or recreational usage, family history, and the presence of Heberden's nodes, the task force concluded.

Although plain radiography of the knee (including a weight-bearing view, a semiflexed view, and lateral and skyline views) remains the standard imaging modality for morphologic assessment of knee OA, imaging is an adjunct for diagnostic purposes. Other imaging modalities, such as MRI, sonography, and scintigraphy, are “seldom indicated for diagnosis of OA,” according to the authors. Classic radiographic features “are focal joint space narrowing, osteophyte, subchondral bone sclerosis, and subchondral cysts.”

Other recommendations cover the definition of knee OA, subsets of the disease, typical symptoms and signs, the use of laboratory tests, and differential diagnosis:

▸ Knee OA is a common, complex joint disorder that is characterized clinically by usage-related pain and functional limitation. The disorder entails focal cartilage loss, new bone formation, and involvement of all joint tissues—changes that are mirrored radiographically.

▸ Subsets of knee OA are associated with different risk factors and outcomes, and can be defined by compartmental involvement, bone response, the global pattern of OA, crystal presence, and the degree of inflammation. However, “the ability to discriminate subsets and the relevance for routine practice are unclear,” the task force noted.

▸ The typical symptoms of knee OA are often episodic, variable in severity, and slow to change. Night pain and more persistent pain at rest may indicate advanced OA.

▸ In addition to the key findings indicative of knee OA (crepitus, restricted movement, and bony enlargement), additional features may include deformity, instability, periarticular or joint-line tenderness, and pain on patellofemoral compression.

▸ Such features as severe local inflammation, erythema, and progressive pain unrelated to usage should raise red flags, as they suggest sepsis, crystals, or serious bone pathology.

▸ Laboratory tests on blood, urine, or synovial fluid are not required for the diagnosis of knee OA, but they may be used to confirm or exclude other inflammatory conditions.

▸ Synovial fluid should be aspirated and analyzed if a palpable effusion is present, in order to confirm or exclude inflammatory disease and identify urate and calcium pyrophosphate crystals.

The authors acknowledged that the recommendations are limited because they were derived from literature based on different studies; the likelihood ratios pooled from the literature may be affected by multiple factors, including the number of studies, the populations considered, and the cutoff values selected; and there was no universally applicable reference standard for knee OA. Also, the recommendations could be different for “less typical” patients younger than age 40 years.

Dr. Zhang reported having no relevant financial relationships to disclose.

A confident diagnosis of knee osteoarthritis can be made without radiographic examination in adults older than 40 years based on criteria described in evidence-based recommendations to be published by the European League Against Rheumatism.

The criteria include usage-related knee pain, short-lived morning stiffness, functional limitation, and one or more “typical” examination findings, such as crepitus, restricted movement, and bony enlargement.

Clinical signs, symptoms, risk factors, and plain radiography are the cornerstones of the recommendations, which have a focus on clinical diagnosis that distinguishes them from the American College of Rheumatology criteria, said Weiya Zhang, Ph.D., of the University of Nottingham (England). He is lead author of the recommendations, which were presented at the annual European Congress of Rheumatology in Copenhagen and are slated for publication in an upcoming issue of the Annals of Rheumatic Disease.

The recommendations were developed by a task force of 17 osteoarthritis experts from 12 European countries. A systematic literature search was undertaken to identify the best available evidence, which was combined with clinical expertise in gauging the strength of each recommendation. Diagnostic accuracy was tested using multiple predictive models in two populations, including one from the Netherlands and one from the United Kingdom, Dr. Zhang explained.

The risk factors found to be strongly associated with knee OA in patients with knee pain include age older than 50 years, female sex, high body mass index, previous knee injury or malalignment, joint laxity, occupational or recreational usage, family history, and the presence of Heberden's nodes, the task force concluded.

Although plain radiography of the knee (including a weight-bearing view, a semiflexed view, and lateral and skyline views) remains the standard imaging modality for morphologic assessment of knee OA, imaging is an adjunct for diagnostic purposes. Other imaging modalities, such as MRI, sonography, and scintigraphy, are “seldom indicated for diagnosis of OA,” according to the authors. Classic radiographic features “are focal joint space narrowing, osteophyte, subchondral bone sclerosis, and subchondral cysts.”

Other recommendations cover the definition of knee OA, subsets of the disease, typical symptoms and signs, the use of laboratory tests, and differential diagnosis:

▸ Knee OA is a common, complex joint disorder that is characterized clinically by usage-related pain and functional limitation. The disorder entails focal cartilage loss, new bone formation, and involvement of all joint tissues—changes that are mirrored radiographically.

▸ Subsets of knee OA are associated with different risk factors and outcomes, and can be defined by compartmental involvement, bone response, the global pattern of OA, crystal presence, and the degree of inflammation. However, “the ability to discriminate subsets and the relevance for routine practice are unclear,” the task force noted.

▸ The typical symptoms of knee OA are often episodic, variable in severity, and slow to change. Night pain and more persistent pain at rest may indicate advanced OA.

▸ In addition to the key findings indicative of knee OA (crepitus, restricted movement, and bony enlargement), additional features may include deformity, instability, periarticular or joint-line tenderness, and pain on patellofemoral compression.

▸ Such features as severe local inflammation, erythema, and progressive pain unrelated to usage should raise red flags, as they suggest sepsis, crystals, or serious bone pathology.

▸ Laboratory tests on blood, urine, or synovial fluid are not required for the diagnosis of knee OA, but they may be used to confirm or exclude other inflammatory conditions.

▸ Synovial fluid should be aspirated and analyzed if a palpable effusion is present, in order to confirm or exclude inflammatory disease and identify urate and calcium pyrophosphate crystals.

The authors acknowledged that the recommendations are limited because they were derived from literature based on different studies; the likelihood ratios pooled from the literature may be affected by multiple factors, including the number of studies, the populations considered, and the cutoff values selected; and there was no universally applicable reference standard for knee OA. Also, the recommendations could be different for “less typical” patients younger than age 40 years.

Dr. Zhang reported having no relevant financial relationships to disclose.

COPENHAGEN — Reduced responses to pneumococcal polysaccharide and neoantigen vaccination in rheumatoid arthritis patients who were treated with rituximab and methotrexate suggest that polysaccharide and primary immunizations should be administered before rituximab infusions to maximize their efficacy, Dr. Clifton O. Bingham III said at the annual European Congress of Rheumatology.

Presenting data from SIERRA (Study Investigating the Effects of Rituximab on Rheumatoid Arthritis Patients), Dr. Bingham, director of the rheumatology clinics at John Hopkins University in Baltimore, reported that relative to patients treated with methotrexate only, patients who were given rituximab plus methotrexate mount a comparable recall response to tetanus toxoid, a measure of retained immunity. Patients on combination therapy also showed preserved delayed-type hypersensitivity (DTH) responses to the Candida albicans skin test.

However, patients on combination therapy showed decreased responses to both the 23-valent pneumococcal polysaccharide vaccine (PPV23), which measures T cell–independent humoral responses, and the neoantigen keyhole limpet hemocyanin (KLH), which tests T cell–dependent primary humoral responses.

The multicenter trial included 103 patients with active RA who were stratified by age and randomized 2:1 to receive two 1,000-mg infusions of rituximab 14 days apart plus methotrexate, or methotrexate alone. Patients aged 18-65 years were included in the study if they had at least four swollen and five tender joints and had been on stable doses of methotrexate for more than 4 weeks, Dr. Bingham explained.

Individuals older than 65 years were excluded from the study “because of the known effect of aging on immune responses,” Dr. Bingham stated. Patients who received the pneumococcal or tetanus vaccine within the previous 3-5 years, and those with other uncontrolled illnesses or concurrent use of other disease-modifying antirheumatic drugs or biologics were also excluded, he said.

The methotrexate-only patients received the tetanus toxoid–adsorbed vaccine on day 1, the PPV23 at week 4, and KLH at weeks 8 and 9, whereas the rituximab group received the same vaccines in the same intervals beginning at week 24, Dr. Bingham said. The C. albicans skin test was administered on day 1 to both groups and then again at week 12 in the methotrexate-only group and at week 24 in the rituximab group.

The study's primary end point was the proportion of patients with a fourfold increase in antitetanus IgG from prevaccination levels, measured 4 weeks after immunization, Dr. Bingham said. Secondary end points included a twofold increase in tetanus toxoid titer; a twofold increase or an increase of more than one mcg/mL from prevaccination levels in immune response to the PPV23; postvaccination KLH titers; and postvaccination DTH reactions, based on a C. albicans skin test with a cutoff of 5 mm of induration, he said.

At baseline, the patients in both groups were similarly matched except for baseline steroid use and positive skin test, Dr. Bingham noted. Baseline steroid use was 42% in the rituximab group and 19% in the methotrexate-only group, whereas the proportion of patients with a positive skin test was 48% in the rituximab group and 71% in the methotrexate-only population, he said.

An evaluation of B cells in the rituximab group at the time of vaccine administration showed that “peripheral B-cell depletion was as expected,” Dr. Bingham said. “At 24 weeks, when the tetanus toxoid was administered, 92% of the patients remained B cell depleted; at 28 weeks, when the pneumococcus vaccine was given, 89% were B cell depleted; and at 36 weeks, when the KLH was given, 76% of the patients were B cell depleted.”

Regarding the study end points, there was no significant difference between the methotrexate-only patients and the rituximab patients in their responses to the tetanus vaccine at either the fourfold or twofold titer increase thresholds, Dr. Bingham said. “What was striking, actually, is that even in patients treated with methotrexate only, the tetanus responses were somewhat low, with only 39% of the rituximab-treated group and 42% of the methotrexate-only group demonstrating a fourfold titer rise.”

An evaluation of the secondary end points showed that significantly fewer of the rituximab patients responded to at least one pneumococcal serotype of the PPV23 (57% vs. 82% of the methotrexate-only group) and to KLH (47% vs. 93%), Dr. Bingham said. “The mean titers were also lower in the rituximab-treated patients,” he said.

Although many patients in the rituximab group were able to mount an immune response to the vaccinations, “it did appear that neoantigen responses to KLH and T cell–independent responses to pneumococcal polysaccharide vaccination were decreased,” Dr. Bingham said. The only significant predictor of vaccine response was IgG2 level at the time of immunization for tetanus, PPV23, and KLH vaccines, he said, noting that “age, methotrexate dose, concomitant corticosteroid use, diagnosis of diabetes mellitus, skin test anergy [less than 5 mm induration], IgM, IgA, total IgG, and IgG1, IgG3, and IgG4 subsets were not predictors of immunization response, nor did rituximab affect total IgG or IgG2 levels.”

The findings provide a rationale for administering polysaccharide and primary immunizations before rituximab infusions in RA patients, Dr. Bingham concluded. During the question-and-answer session, he agreed that in some patients in whom pretreatment immunization is not feasible, reimmunization may boost the level of immune response. “Even during the period of B-cell depletion, 57% of the rituximab group did respond to at least one serotype and 42% responded to at least two serotypes, so there is some efficacy,” he said.

Dr. Bingham has served as a consultant to Genentech Inc. and to Roche.

This provides a rationale for administering polysaccharide and primary immunizations before rituximab.

Source Dr. Bingham

COPENHAGEN — Reduced responses to pneumococcal polysaccharide and neoantigen vaccination in rheumatoid arthritis patients who were treated with rituximab and methotrexate suggest that polysaccharide and primary immunizations should be administered before rituximab infusions to maximize their efficacy, Dr. Clifton O. Bingham III said at the annual European Congress of Rheumatology.

Presenting data from SIERRA (Study Investigating the Effects of Rituximab on Rheumatoid Arthritis Patients), Dr. Bingham, director of the rheumatology clinics at John Hopkins University in Baltimore, reported that relative to patients treated with methotrexate only, patients who were given rituximab plus methotrexate mount a comparable recall response to tetanus toxoid, a measure of retained immunity. Patients on combination therapy also showed preserved delayed-type hypersensitivity (DTH) responses to the Candida albicans skin test.

However, patients on combination therapy showed decreased responses to both the 23-valent pneumococcal polysaccharide vaccine (PPV23), which measures T cell–independent humoral responses, and the neoantigen keyhole limpet hemocyanin (KLH), which tests T cell–dependent primary humoral responses.

The multicenter trial included 103 patients with active RA who were stratified by age and randomized 2:1 to receive two 1,000-mg infusions of rituximab 14 days apart plus methotrexate, or methotrexate alone. Patients aged 18-65 years were included in the study if they had at least four swollen and five tender joints and had been on stable doses of methotrexate for more than 4 weeks, Dr. Bingham explained.

Individuals older than 65 years were excluded from the study “because of the known effect of aging on immune responses,” Dr. Bingham stated. Patients who received the pneumococcal or tetanus vaccine within the previous 3-5 years, and those with other uncontrolled illnesses or concurrent use of other disease-modifying antirheumatic drugs or biologics were also excluded, he said.

The methotrexate-only patients received the tetanus toxoid–adsorbed vaccine on day 1, the PPV23 at week 4, and KLH at weeks 8 and 9, whereas the rituximab group received the same vaccines in the same intervals beginning at week 24, Dr. Bingham said. The C. albicans skin test was administered on day 1 to both groups and then again at week 12 in the methotrexate-only group and at week 24 in the rituximab group.

The study's primary end point was the proportion of patients with a fourfold increase in antitetanus IgG from prevaccination levels, measured 4 weeks after immunization, Dr. Bingham said. Secondary end points included a twofold increase in tetanus toxoid titer; a twofold increase or an increase of more than one mcg/mL from prevaccination levels in immune response to the PPV23; postvaccination KLH titers; and postvaccination DTH reactions, based on a C. albicans skin test with a cutoff of 5 mm of induration, he said.

At baseline, the patients in both groups were similarly matched except for baseline steroid use and positive skin test, Dr. Bingham noted. Baseline steroid use was 42% in the rituximab group and 19% in the methotrexate-only group, whereas the proportion of patients with a positive skin test was 48% in the rituximab group and 71% in the methotrexate-only population, he said.

An evaluation of B cells in the rituximab group at the time of vaccine administration showed that “peripheral B-cell depletion was as expected,” Dr. Bingham said. “At 24 weeks, when the tetanus toxoid was administered, 92% of the patients remained B cell depleted; at 28 weeks, when the pneumococcus vaccine was given, 89% were B cell depleted; and at 36 weeks, when the KLH was given, 76% of the patients were B cell depleted.”

Regarding the study end points, there was no significant difference between the methotrexate-only patients and the rituximab patients in their responses to the tetanus vaccine at either the fourfold or twofold titer increase thresholds, Dr. Bingham said. “What was striking, actually, is that even in patients treated with methotrexate only, the tetanus responses were somewhat low, with only 39% of the rituximab-treated group and 42% of the methotrexate-only group demonstrating a fourfold titer rise.”

An evaluation of the secondary end points showed that significantly fewer of the rituximab patients responded to at least one pneumococcal serotype of the PPV23 (57% vs. 82% of the methotrexate-only group) and to KLH (47% vs. 93%), Dr. Bingham said. “The mean titers were also lower in the rituximab-treated patients,” he said.

Although many patients in the rituximab group were able to mount an immune response to the vaccinations, “it did appear that neoantigen responses to KLH and T cell–independent responses to pneumococcal polysaccharide vaccination were decreased,” Dr. Bingham said. The only significant predictor of vaccine response was IgG2 level at the time of immunization for tetanus, PPV23, and KLH vaccines, he said, noting that “age, methotrexate dose, concomitant corticosteroid use, diagnosis of diabetes mellitus, skin test anergy [less than 5 mm induration], IgM, IgA, total IgG, and IgG1, IgG3, and IgG4 subsets were not predictors of immunization response, nor did rituximab affect total IgG or IgG2 levels.”

The findings provide a rationale for administering polysaccharide and primary immunizations before rituximab infusions in RA patients, Dr. Bingham concluded. During the question-and-answer session, he agreed that in some patients in whom pretreatment immunization is not feasible, reimmunization may boost the level of immune response. “Even during the period of B-cell depletion, 57% of the rituximab group did respond to at least one serotype and 42% responded to at least two serotypes, so there is some efficacy,” he said.

Dr. Bingham has served as a consultant to Genentech Inc. and to Roche.

This provides a rationale for administering polysaccharide and primary immunizations before rituximab.

Source Dr. Bingham

COPENHAGEN — Reduced responses to pneumococcal polysaccharide and neoantigen vaccination in rheumatoid arthritis patients who were treated with rituximab and methotrexate suggest that polysaccharide and primary immunizations should be administered before rituximab infusions to maximize their efficacy, Dr. Clifton O. Bingham III said at the annual European Congress of Rheumatology.

Presenting data from SIERRA (Study Investigating the Effects of Rituximab on Rheumatoid Arthritis Patients), Dr. Bingham, director of the rheumatology clinics at John Hopkins University in Baltimore, reported that relative to patients treated with methotrexate only, patients who were given rituximab plus methotrexate mount a comparable recall response to tetanus toxoid, a measure of retained immunity. Patients on combination therapy also showed preserved delayed-type hypersensitivity (DTH) responses to the Candida albicans skin test.

However, patients on combination therapy showed decreased responses to both the 23-valent pneumococcal polysaccharide vaccine (PPV23), which measures T cell–independent humoral responses, and the neoantigen keyhole limpet hemocyanin (KLH), which tests T cell–dependent primary humoral responses.

The multicenter trial included 103 patients with active RA who were stratified by age and randomized 2:1 to receive two 1,000-mg infusions of rituximab 14 days apart plus methotrexate, or methotrexate alone. Patients aged 18-65 years were included in the study if they had at least four swollen and five tender joints and had been on stable doses of methotrexate for more than 4 weeks, Dr. Bingham explained.

Individuals older than 65 years were excluded from the study “because of the known effect of aging on immune responses,” Dr. Bingham stated. Patients who received the pneumococcal or tetanus vaccine within the previous 3-5 years, and those with other uncontrolled illnesses or concurrent use of other disease-modifying antirheumatic drugs or biologics were also excluded, he said.

The methotrexate-only patients received the tetanus toxoid–adsorbed vaccine on day 1, the PPV23 at week 4, and KLH at weeks 8 and 9, whereas the rituximab group received the same vaccines in the same intervals beginning at week 24, Dr. Bingham said. The C. albicans skin test was administered on day 1 to both groups and then again at week 12 in the methotrexate-only group and at week 24 in the rituximab group.

The study's primary end point was the proportion of patients with a fourfold increase in antitetanus IgG from prevaccination levels, measured 4 weeks after immunization, Dr. Bingham said. Secondary end points included a twofold increase in tetanus toxoid titer; a twofold increase or an increase of more than one mcg/mL from prevaccination levels in immune response to the PPV23; postvaccination KLH titers; and postvaccination DTH reactions, based on a C. albicans skin test with a cutoff of 5 mm of induration, he said.

At baseline, the patients in both groups were similarly matched except for baseline steroid use and positive skin test, Dr. Bingham noted. Baseline steroid use was 42% in the rituximab group and 19% in the methotrexate-only group, whereas the proportion of patients with a positive skin test was 48% in the rituximab group and 71% in the methotrexate-only population, he said.

An evaluation of B cells in the rituximab group at the time of vaccine administration showed that “peripheral B-cell depletion was as expected,” Dr. Bingham said. “At 24 weeks, when the tetanus toxoid was administered, 92% of the patients remained B cell depleted; at 28 weeks, when the pneumococcus vaccine was given, 89% were B cell depleted; and at 36 weeks, when the KLH was given, 76% of the patients were B cell depleted.”

Regarding the study end points, there was no significant difference between the methotrexate-only patients and the rituximab patients in their responses to the tetanus vaccine at either the fourfold or twofold titer increase thresholds, Dr. Bingham said. “What was striking, actually, is that even in patients treated with methotrexate only, the tetanus responses were somewhat low, with only 39% of the rituximab-treated group and 42% of the methotrexate-only group demonstrating a fourfold titer rise.”

An evaluation of the secondary end points showed that significantly fewer of the rituximab patients responded to at least one pneumococcal serotype of the PPV23 (57% vs. 82% of the methotrexate-only group) and to KLH (47% vs. 93%), Dr. Bingham said. “The mean titers were also lower in the rituximab-treated patients,” he said.

Although many patients in the rituximab group were able to mount an immune response to the vaccinations, “it did appear that neoantigen responses to KLH and T cell–independent responses to pneumococcal polysaccharide vaccination were decreased,” Dr. Bingham said. The only significant predictor of vaccine response was IgG2 level at the time of immunization for tetanus, PPV23, and KLH vaccines, he said, noting that “age, methotrexate dose, concomitant corticosteroid use, diagnosis of diabetes mellitus, skin test anergy [less than 5 mm induration], IgM, IgA, total IgG, and IgG1, IgG3, and IgG4 subsets were not predictors of immunization response, nor did rituximab affect total IgG or IgG2 levels.”

The findings provide a rationale for administering polysaccharide and primary immunizations before rituximab infusions in RA patients, Dr. Bingham concluded. During the question-and-answer session, he agreed that in some patients in whom pretreatment immunization is not feasible, reimmunization may boost the level of immune response. “Even during the period of B-cell depletion, 57% of the rituximab group did respond to at least one serotype and 42% responded to at least two serotypes, so there is some efficacy,” he said.

Dr. Bingham has served as a consultant to Genentech Inc. and to Roche.

This provides a rationale for administering polysaccharide and primary immunizations before rituximab.

Source Dr. Bingham

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

“Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk,” Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781–6).

Further, Merck's marketing strategy included awarding “sizeable educational grants” to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. “We did not require any reporting or review of any materials developed,” Ms. Eisele said. “Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences. Merck did not have any input or influence over the content of the materials those organizations developed.”

“We value our relationships with these groups and conduct our interactions with strict adherence to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals,” said Ms. Eisele. In addition, “Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education.”

Dr. Rothman and Dr. Rothman charged that the role of several professional medical associations in the marketing of the HPV vaccine “is cause for concern.”

Professional medical associations “must become more transparent about their relationships with industry, disclosing both the precise funding and technical assistance they have received to develop and disseminate the promotional products.”

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a day-long program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said. The society also “arranged opportunities for CME-accredited courses” through various venues.

Attendees of the ASCCP educational program receive a Speaker Lecture Kit of nearly 200 slides with information on cervical cancer risk for medical and lay audiences as well as strategies for convincing government agencies to mandate HPV vaccination and for convincing insurers to pay for the vaccine, the editorialists noted. One of the slides recommended downplaying the fact that HPV is a sexually transmitted infection to minimize parental discomfort, according to Dr. Rothman and Dr. Rothman.

The ASCCP's member clinicians “have little occasion to recommend or deliver immunization,” and could potentially see a negative economic benefit from a successful vaccination effort, yet “ASCCP leaders perceived vaccine promotion as an opportunity to turn a potential financial liability into an asset,” and to re-energize its society, according to Dr. Rothman and Dr. Rothman.

“That is not the case,” Dr. L. Stewart Massad, chair of the ASCCP's Practice and Ethics committees, said in an interview. “We have long recognized that the current [cervical cancer] prevention system is flawed. Although prevention based on Pap testing, colposcopy, and destruction of precursors is effective, it is expensive, intrusive, insensitive, and nonspecific, and it results in the overtreatment of thousands of women each year.”

Given the potential for conflicts of interest associated with an industry-supported educational program, “we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently,” Dr. Massad said, noting that he accepts no financial support or grant money.

Merck also gave grant money to the Society of Gynecologic Oncologists (SGO).

Dr. Rothman and Dr. Rothman wrote that the SGO was concerned about its future as a subspecialty and perceived the HPV marketing opportunity as a way to springboard its transformation from a surgically based to a medically based discipline. The organization used the funding from Merck and other companies to create a physician education campaign, which was overseen by a resource panel that included some members with financial ties to Merck.

The materials created by the SGO panel “omitted cautionary qualifications,” according to Dr. Rothman and Dr. Rothman. Further, the materials “did not include data on disparities in cervical cancer incidence and outcomes,” nor did it include questions about the vaccine's history and efficacy, whether the risks outweigh the benefits, or a discussion of the continued need for Pap tests.

Additionally, as part of the sponsorship agreement with Merck, society members who used the teaching materials were required to report to the society where and when they presented the material, Dr. Rothman and Dr. Rothman said.

The American College of Obstetricians and Gynecologists also received grant money for HPV vaccine education.

In an interview, Dr. Hal C. Lawrence III, vice president of practice activities for ACOG, emphasized that the college “thoroughly reviewed the evidence before making any recommendations about the HPV vaccine.”

“We wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine, both in the prevention of cervical cancer but also in other HPV illnesses,” he said. “Although the incidence of cervical cancer has diminished dramatically, the incidence of venereal warts, condyloma, and abnormal Pap tests is still significant.”

Dr. Rothman and Dr. Rothman concluded that professional medical associations should refrain from promoting product-specific speakers bureaus and refuse funding that requires reporting activity to the donor.

Neither reported having relevant financial disclosures.

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

“Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk,” Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781–6).

Further, Merck's marketing strategy included awarding “sizeable educational grants” to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. “We did not require any reporting or review of any materials developed,” Ms. Eisele said. “Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences. Merck did not have any input or influence over the content of the materials those organizations developed.”

“We value our relationships with these groups and conduct our interactions with strict adherence to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals,” said Ms. Eisele. In addition, “Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education.”

Dr. Rothman and Dr. Rothman charged that the role of several professional medical associations in the marketing of the HPV vaccine “is cause for concern.”

Professional medical associations “must become more transparent about their relationships with industry, disclosing both the precise funding and technical assistance they have received to develop and disseminate the promotional products.”

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a day-long program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said. The society also “arranged opportunities for CME-accredited courses” through various venues.

Attendees of the ASCCP educational program receive a Speaker Lecture Kit of nearly 200 slides with information on cervical cancer risk for medical and lay audiences as well as strategies for convincing government agencies to mandate HPV vaccination and for convincing insurers to pay for the vaccine, the editorialists noted. One of the slides recommended downplaying the fact that HPV is a sexually transmitted infection to minimize parental discomfort, according to Dr. Rothman and Dr. Rothman.

The ASCCP's member clinicians “have little occasion to recommend or deliver immunization,” and could potentially see a negative economic benefit from a successful vaccination effort, yet “ASCCP leaders perceived vaccine promotion as an opportunity to turn a potential financial liability into an asset,” and to re-energize its society, according to Dr. Rothman and Dr. Rothman.

“That is not the case,” Dr. L. Stewart Massad, chair of the ASCCP's Practice and Ethics committees, said in an interview. “We have long recognized that the current [cervical cancer] prevention system is flawed. Although prevention based on Pap testing, colposcopy, and destruction of precursors is effective, it is expensive, intrusive, insensitive, and nonspecific, and it results in the overtreatment of thousands of women each year.”

Given the potential for conflicts of interest associated with an industry-supported educational program, “we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently,” Dr. Massad said, noting that he accepts no financial support or grant money.

Merck also gave grant money to the Society of Gynecologic Oncologists (SGO).

Dr. Rothman and Dr. Rothman wrote that the SGO was concerned about its future as a subspecialty and perceived the HPV marketing opportunity as a way to springboard its transformation from a surgically based to a medically based discipline. The organization used the funding from Merck and other companies to create a physician education campaign, which was overseen by a resource panel that included some members with financial ties to Merck.

The materials created by the SGO panel “omitted cautionary qualifications,” according to Dr. Rothman and Dr. Rothman. Further, the materials “did not include data on disparities in cervical cancer incidence and outcomes,” nor did it include questions about the vaccine's history and efficacy, whether the risks outweigh the benefits, or a discussion of the continued need for Pap tests.

Additionally, as part of the sponsorship agreement with Merck, society members who used the teaching materials were required to report to the society where and when they presented the material, Dr. Rothman and Dr. Rothman said.

The American College of Obstetricians and Gynecologists also received grant money for HPV vaccine education.

In an interview, Dr. Hal C. Lawrence III, vice president of practice activities for ACOG, emphasized that the college “thoroughly reviewed the evidence before making any recommendations about the HPV vaccine.”

“We wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine, both in the prevention of cervical cancer but also in other HPV illnesses,” he said. “Although the incidence of cervical cancer has diminished dramatically, the incidence of venereal warts, condyloma, and abnormal Pap tests is still significant.”

Dr. Rothman and Dr. Rothman concluded that professional medical associations should refrain from promoting product-specific speakers bureaus and refuse funding that requires reporting activity to the donor.

Neither reported having relevant financial disclosures.

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

“Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk,” Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781–6).

Further, Merck's marketing strategy included awarding “sizeable educational grants” to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. “We did not require any reporting or review of any materials developed,” Ms. Eisele said. “Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences. Merck did not have any input or influence over the content of the materials those organizations developed.”

“We value our relationships with these groups and conduct our interactions with strict adherence to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals,” said Ms. Eisele. In addition, “Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education.”

Dr. Rothman and Dr. Rothman charged that the role of several professional medical associations in the marketing of the HPV vaccine “is cause for concern.”

Professional medical associations “must become more transparent about their relationships with industry, disclosing both the precise funding and technical assistance they have received to develop and disseminate the promotional products.”

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a day-long program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said. The society also “arranged opportunities for CME-accredited courses” through various venues.

Attendees of the ASCCP educational program receive a Speaker Lecture Kit of nearly 200 slides with information on cervical cancer risk for medical and lay audiences as well as strategies for convincing government agencies to mandate HPV vaccination and for convincing insurers to pay for the vaccine, the editorialists noted. One of the slides recommended downplaying the fact that HPV is a sexually transmitted infection to minimize parental discomfort, according to Dr. Rothman and Dr. Rothman.

The ASCCP's member clinicians “have little occasion to recommend or deliver immunization,” and could potentially see a negative economic benefit from a successful vaccination effort, yet “ASCCP leaders perceived vaccine promotion as an opportunity to turn a potential financial liability into an asset,” and to re-energize its society, according to Dr. Rothman and Dr. Rothman.

“That is not the case,” Dr. L. Stewart Massad, chair of the ASCCP's Practice and Ethics committees, said in an interview. “We have long recognized that the current [cervical cancer] prevention system is flawed. Although prevention based on Pap testing, colposcopy, and destruction of precursors is effective, it is expensive, intrusive, insensitive, and nonspecific, and it results in the overtreatment of thousands of women each year.”

Given the potential for conflicts of interest associated with an industry-supported educational program, “we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently,” Dr. Massad said, noting that he accepts no financial support or grant money.

Merck also gave grant money to the Society of Gynecologic Oncologists (SGO).

Dr. Rothman and Dr. Rothman wrote that the SGO was concerned about its future as a subspecialty and perceived the HPV marketing opportunity as a way to springboard its transformation from a surgically based to a medically based discipline. The organization used the funding from Merck and other companies to create a physician education campaign, which was overseen by a resource panel that included some members with financial ties to Merck.

The materials created by the SGO panel “omitted cautionary qualifications,” according to Dr. Rothman and Dr. Rothman. Further, the materials “did not include data on disparities in cervical cancer incidence and outcomes,” nor did it include questions about the vaccine's history and efficacy, whether the risks outweigh the benefits, or a discussion of the continued need for Pap tests.

Additionally, as part of the sponsorship agreement with Merck, society members who used the teaching materials were required to report to the society where and when they presented the material, Dr. Rothman and Dr. Rothman said.

The American College of Obstetricians and Gynecologists also received grant money for HPV vaccine education.

In an interview, Dr. Hal C. Lawrence III, vice president of practice activities for ACOG, emphasized that the college “thoroughly reviewed the evidence before making any recommendations about the HPV vaccine.”

“We wouldn't make any recommendations if we didn't feel strongly about the importance of the vaccine, both in the prevention of cervical cancer but also in other HPV illnesses,” he said. “Although the incidence of cervical cancer has diminished dramatically, the incidence of venereal warts, condyloma, and abnormal Pap tests is still significant.”

Dr. Rothman and Dr. Rothman concluded that professional medical associations should refrain from promoting product-specific speakers bureaus and refuse funding that requires reporting activity to the donor.

Neither reported having relevant financial disclosures.

Women taking antidepressants who are thinking about getting pregnant might consider tapering or discontinuing drug therapy if they have experienced only mild or no symptoms for at least 6 months, depending on their psychiatric history, according to a new report on the treatment of depression during pregnancy.

The report, issued jointly by the American Psychiatric Association and the American College of Obstetricians and Gynecologists, also said medication discontinuation might not be appropriate for women with a history of severe recurrent depression or those who have psychosis, bipolar disorder, other psychiatric illness requiring medication, or a history of suicide attempts.

The report was published in the September issue of Obstetrics and Gynecology, and produced by an APA/ACOG work group convened to evaluate and summarize information about the risks associated with depression and antidepressant therapy during pregnancy. Representatives from both professional associations, along with a consulting developmental pediatrician, conducted a critical review of published literature on fetal and neonatal outcomes associated with depression and antidepressant treatment during childbearing.

The authors concluded that the symptoms of depression and exposure to antidepressant therapy might be linked to certain fetal growth and development changes, “but the available research has not yet adequately controlled for other factors that may influence birth outcomes, including maternal illness or problematic health behaviors that can adversely affect pregnancy,” wrote lead author Dr. Kimberly A. Yonkers of Yale University, New Haven, Conn., and her colleagues (Obstet. Gynecol. 2009;114:703–13). The report is being published concurrently in the September/October issue of General Hospital Psychiatry (doi:10.1016/j.genhosppsych.2009.04.003

For preconceptional patients receiving pharmacologic treatment for depression, a determination of the severity of symptoms should guide management recommendations, the authors wrote. Patients with suicidal or acute psychotic symptoms should be referred to a psychiatrist for aggressive treatment and counseled to wait a period of time after achieving euthymia before conceiving.

Similarly, patients with moderate to severe symptoms should continue and optimize antidepressant therapy and wait for a period of time before conceiving.

“While it is difficult to specify an exact or optimal length of time for all patients, guidelines such as those from the [Agency for Healthcare Research and Quality] suggest antidepressant treatment for a first, acute episode of depression should endure at least 6–12 months,” they wrote.

For women with mild or no symptoms for at least 6 months who are candidates for medication discontinuation, the decision to initiate a treatment hiatus should be made in consultation with her psychiatrist, and the subsequent taper should be slow—such as a 25% reduction in dose every 1–2 weeks with close monitoring for relapse, the authors said.

The obstetrical care of women with a history of severe, recurrent mood disorders who continue drug treatment should also be coordinated with the psychiatric provider to monitor for illness relapse, they wrote, noting also that some women may benefit from individual or group psychotherapy, alone or in combination with medication.

Women with untreated depression that is diagnosed during pregnancy and those with depression who have discontinued their medication should similarly be evaluated for symptom severity and, if necessary, referred for psychiatric consultation, according to the report.

For patients with severe depressive, suicidal, or psychotic symptoms, the use of antiepileptic agents, newer antipsychotic drugs, and antidepressants should be avoided in the first trimester, if possible, because of the teratogenic potential of the antiepileptics and relative lack of reproductive safety information for the newer antipsychotics and antidepressants, the authors stated.

Those women who are not “gravely disabled or at high risk of relapse” may benefit from psychotherapy, and those with bipolar affective disorder should be managed by a psychiatrist because of the risk that antidepressant monotherapy could trigger mania and psychosis, they wrote.

In all women who begin antidepressant treatment during pregnancy, the treatment choice should be guided by the drugs' safety profile and the stage of gestation, as well as the patient's symptoms, history, and preferences, the authors stressed.

For women who are taking antidepressant medication when they become pregnant, “if the patient is willing to consider discontinuation of medication and she is not currently having symptoms, then, depending upon the individual's psychiatric history, a trial of medication taper may be appropriate,” the authors wrote. They noted, however, that “women with a history of severe, recurrent depression, even if currently asymptomatic or minimally symptomatic, are at a high risk of relapse if medication is discontinued.” For those women who prefer to continue medication, “discuss risk/benefit issues and document this discussion and the patient's choice, in her medical record,” they advised.

If a woman being treated for severe depression refuses to continue medication, alternative treatment, such as psychotherapy, and close monitoring are advised. Similarly, women with depressive symptoms or recurrent depression despite medication, might benefit from the addition of psychotherapy, the authors wrote.

In addition to the recommendations, the report addresses several frequently asked questions about antidepressant treatment during pregnancy. In evaluating the cumulative research related to antidepressant use in pregnancy, the authors noted several limitations. Specifically, few of the studies that assessed associations between antidepressant treatment and birth outcomes included information on maternal psychiatric illness and confounding factors that influence birth outcomes, such as poor prenatal care and drug, alcohol, and nicotine use, which occur at a higher rate among depressed vs. nondepressed women, were often not controlled.

Some of the report authors disclosed having received research support and consultants fees from various pharmaceutical companies, including Eli Lilly, Pfizer, Wyeth, Boehringer Ingelheim, Bayer Schering Pharma AG, Berlex, and GlaxoSmithKline.

Women taking antidepressants who are thinking about getting pregnant might consider tapering or discontinuing drug therapy if they have experienced only mild or no symptoms for at least 6 months, depending on their psychiatric history, according to a new report on the treatment of depression during pregnancy.

The report, issued jointly by the American Psychiatric Association and the American College of Obstetricians and Gynecologists, also said medication discontinuation might not be appropriate for women with a history of severe recurrent depression or those who have psychosis, bipolar disorder, other psychiatric illness requiring medication, or a history of suicide attempts.

The report was published in the September issue of Obstetrics and Gynecology, and produced by an APA/ACOG work group convened to evaluate and summarize information about the risks associated with depression and antidepressant therapy during pregnancy. Representatives from both professional associations, along with a consulting developmental pediatrician, conducted a critical review of published literature on fetal and neonatal outcomes associated with depression and antidepressant treatment during childbearing.

The authors concluded that the symptoms of depression and exposure to antidepressant therapy might be linked to certain fetal growth and development changes, “but the available research has not yet adequately controlled for other factors that may influence birth outcomes, including maternal illness or problematic health behaviors that can adversely affect pregnancy,” wrote lead author Dr. Kimberly A. Yonkers of Yale University, New Haven, Conn., and her colleagues (Obstet. Gynecol. 2009;114:703–13). The report is being published concurrently in the September/October issue of General Hospital Psychiatry (doi:10.1016/j.genhosppsych.2009.04.003

For preconceptional patients receiving pharmacologic treatment for depression, a determination of the severity of symptoms should guide management recommendations, the authors wrote. Patients with suicidal or acute psychotic symptoms should be referred to a psychiatrist for aggressive treatment and counseled to wait a period of time after achieving euthymia before conceiving.

Similarly, patients with moderate to severe symptoms should continue and optimize antidepressant therapy and wait for a period of time before conceiving.

“While it is difficult to specify an exact or optimal length of time for all patients, guidelines such as those from the [Agency for Healthcare Research and Quality] suggest antidepressant treatment for a first, acute episode of depression should endure at least 6–12 months,” they wrote.

For women with mild or no symptoms for at least 6 months who are candidates for medication discontinuation, the decision to initiate a treatment hiatus should be made in consultation with her psychiatrist, and the subsequent taper should be slow—such as a 25% reduction in dose every 1–2 weeks with close monitoring for relapse, the authors said.

The obstetrical care of women with a history of severe, recurrent mood disorders who continue drug treatment should also be coordinated with the psychiatric provider to monitor for illness relapse, they wrote, noting also that some women may benefit from individual or group psychotherapy, alone or in combination with medication.

Women with untreated depression that is diagnosed during pregnancy and those with depression who have discontinued their medication should similarly be evaluated for symptom severity and, if necessary, referred for psychiatric consultation, according to the report.

For patients with severe depressive, suicidal, or psychotic symptoms, the use of antiepileptic agents, newer antipsychotic drugs, and antidepressants should be avoided in the first trimester, if possible, because of the teratogenic potential of the antiepileptics and relative lack of reproductive safety information for the newer antipsychotics and antidepressants, the authors stated.

Those women who are not “gravely disabled or at high risk of relapse” may benefit from psychotherapy, and those with bipolar affective disorder should be managed by a psychiatrist because of the risk that antidepressant monotherapy could trigger mania and psychosis, they wrote.

In all women who begin antidepressant treatment during pregnancy, the treatment choice should be guided by the drugs' safety profile and the stage of gestation, as well as the patient's symptoms, history, and preferences, the authors stressed.

For women who are taking antidepressant medication when they become pregnant, “if the patient is willing to consider discontinuation of medication and she is not currently having symptoms, then, depending upon the individual's psychiatric history, a trial of medication taper may be appropriate,” the authors wrote. They noted, however, that “women with a history of severe, recurrent depression, even if currently asymptomatic or minimally symptomatic, are at a high risk of relapse if medication is discontinued.” For those women who prefer to continue medication, “discuss risk/benefit issues and document this discussion and the patient's choice, in her medical record,” they advised.

If a woman being treated for severe depression refuses to continue medication, alternative treatment, such as psychotherapy, and close monitoring are advised. Similarly, women with depressive symptoms or recurrent depression despite medication, might benefit from the addition of psychotherapy, the authors wrote.

In addition to the recommendations, the report addresses several frequently asked questions about antidepressant treatment during pregnancy. In evaluating the cumulative research related to antidepressant use in pregnancy, the authors noted several limitations. Specifically, few of the studies that assessed associations between antidepressant treatment and birth outcomes included information on maternal psychiatric illness and confounding factors that influence birth outcomes, such as poor prenatal care and drug, alcohol, and nicotine use, which occur at a higher rate among depressed vs. nondepressed women, were often not controlled.

Some of the report authors disclosed having received research support and consultants fees from various pharmaceutical companies, including Eli Lilly, Pfizer, Wyeth, Boehringer Ingelheim, Bayer Schering Pharma AG, Berlex, and GlaxoSmithKline.

Women taking antidepressants who are thinking about getting pregnant might consider tapering or discontinuing drug therapy if they have experienced only mild or no symptoms for at least 6 months, depending on their psychiatric history, according to a new report on the treatment of depression during pregnancy.

The report, issued jointly by the American Psychiatric Association and the American College of Obstetricians and Gynecologists, also said medication discontinuation might not be appropriate for women with a history of severe recurrent depression or those who have psychosis, bipolar disorder, other psychiatric illness requiring medication, or a history of suicide attempts.

The report was published in the September issue of Obstetrics and Gynecology, and produced by an APA/ACOG work group convened to evaluate and summarize information about the risks associated with depression and antidepressant therapy during pregnancy. Representatives from both professional associations, along with a consulting developmental pediatrician, conducted a critical review of published literature on fetal and neonatal outcomes associated with depression and antidepressant treatment during childbearing.

The authors concluded that the symptoms of depression and exposure to antidepressant therapy might be linked to certain fetal growth and development changes, “but the available research has not yet adequately controlled for other factors that may influence birth outcomes, including maternal illness or problematic health behaviors that can adversely affect pregnancy,” wrote lead author Dr. Kimberly A. Yonkers of Yale University, New Haven, Conn., and her colleagues (Obstet. Gynecol. 2009;114:703–13). The report is being published concurrently in the September/October issue of General Hospital Psychiatry (doi:10.1016/j.genhosppsych.2009.04.003

For preconceptional patients receiving pharmacologic treatment for depression, a determination of the severity of symptoms should guide management recommendations, the authors wrote. Patients with suicidal or acute psychotic symptoms should be referred to a psychiatrist for aggressive treatment and counseled to wait a period of time after achieving euthymia before conceiving.

Similarly, patients with moderate to severe symptoms should continue and optimize antidepressant therapy and wait for a period of time before conceiving.

“While it is difficult to specify an exact or optimal length of time for all patients, guidelines such as those from the [Agency for Healthcare Research and Quality] suggest antidepressant treatment for a first, acute episode of depression should endure at least 6–12 months,” they wrote.

For women with mild or no symptoms for at least 6 months who are candidates for medication discontinuation, the decision to initiate a treatment hiatus should be made in consultation with her psychiatrist, and the subsequent taper should be slow—such as a 25% reduction in dose every 1–2 weeks with close monitoring for relapse, the authors said.

The obstetrical care of women with a history of severe, recurrent mood disorders who continue drug treatment should also be coordinated with the psychiatric provider to monitor for illness relapse, they wrote, noting also that some women may benefit from individual or group psychotherapy, alone or in combination with medication.

Women with untreated depression that is diagnosed during pregnancy and those with depression who have discontinued their medication should similarly be evaluated for symptom severity and, if necessary, referred for psychiatric consultation, according to the report.

For patients with severe depressive, suicidal, or psychotic symptoms, the use of antiepileptic agents, newer antipsychotic drugs, and antidepressants should be avoided in the first trimester, if possible, because of the teratogenic potential of the antiepileptics and relative lack of reproductive safety information for the newer antipsychotics and antidepressants, the authors stated.

Those women who are not “gravely disabled or at high risk of relapse” may benefit from psychotherapy, and those with bipolar affective disorder should be managed by a psychiatrist because of the risk that antidepressant monotherapy could trigger mania and psychosis, they wrote.

In all women who begin antidepressant treatment during pregnancy, the treatment choice should be guided by the drugs' safety profile and the stage of gestation, as well as the patient's symptoms, history, and preferences, the authors stressed.

For women who are taking antidepressant medication when they become pregnant, “if the patient is willing to consider discontinuation of medication and she is not currently having symptoms, then, depending upon the individual's psychiatric history, a trial of medication taper may be appropriate,” the authors wrote. They noted, however, that “women with a history of severe, recurrent depression, even if currently asymptomatic or minimally symptomatic, are at a high risk of relapse if medication is discontinued.” For those women who prefer to continue medication, “discuss risk/benefit issues and document this discussion and the patient's choice, in her medical record,” they advised.

If a woman being treated for severe depression refuses to continue medication, alternative treatment, such as psychotherapy, and close monitoring are advised. Similarly, women with depressive symptoms or recurrent depression despite medication, might benefit from the addition of psychotherapy, the authors wrote.

In addition to the recommendations, the report addresses several frequently asked questions about antidepressant treatment during pregnancy. In evaluating the cumulative research related to antidepressant use in pregnancy, the authors noted several limitations. Specifically, few of the studies that assessed associations between antidepressant treatment and birth outcomes included information on maternal psychiatric illness and confounding factors that influence birth outcomes, such as poor prenatal care and drug, alcohol, and nicotine use, which occur at a higher rate among depressed vs. nondepressed women, were often not controlled.

Some of the report authors disclosed having received research support and consultants fees from various pharmaceutical companies, including Eli Lilly, Pfizer, Wyeth, Boehringer Ingelheim, Bayer Schering Pharma AG, Berlex, and GlaxoSmithKline.

COPENHAGEN — Prednisone in initial dosages lower than 5 mg/day is as effective as higher doses in rheumatoid arthritis patients, a study has shown.

Although the use of glucocorticoids in RA remains controversial, the drugs continue to play a major role in the treatment of the disease, Dr. Theodore Pincus said at the annual European Congress of Rheumatology. “Textbooks suggest that glucocorticoids should be used in rheumatoid arthritis only for patients with life-threatening complications, or as a bridge therapy until [disease modifying antirheumatic drug] treatment begins to work, yet estimates suggest that they are used by 20%-80% of patients in usual clinical practice.” Therefore, he noted, determining the lowest effective dosage is important.

Toward this end, Dr. Pincus, clinical professor of medicine at New York University and the Hospital for Joint Diseases, New York, and his colleagues retrospectively analyzed the efficacy of prednisone in the usual care of 308 RA patients treated over a 25-year period. Using a database of all patient visits to a weekly academic clinic during 1980-2004, the investigators analyzed all initial prednisone prescriptions and classified patients into those treated with an initial prednisone dosage of 5 mg/day or higher and those treated with an initial dose lower than 5 mg/day. The 5-mg threshold was used because the efficacy of prednisone at 5 mg daily in RA has been documented, according to Dr. Pincus.

Of the 308 patients, 195 were treated with an initial prednisone dose of 5 mg or higher and 113 were treated with an initial dose less than 5 mg. Nearly all of the patients taking prednisone also took DMARDs, primarily methotrexate.

All of the patients in the study completed the MDHAQ-FN (Multidimensional Health Assessment Questionnaire including physical function measures), and a VAS (Visual Analog Scale) pain measure at each visit. The investigators compared the baseline, 12-month, and 24-month follow-up scores of patients in both dosage groups and used the change in scores from baseline to 12 and 24 months as outcome measures. They also analyzed the data based on 5-year subgroups to account for changes in prescribing practices over time. At baseline, patients in the higher-dose group had higher function and pain scores than did those in the lower-dose group, Dr. Pincus noted in a poster presentation.

The mean improvements in MDHAQ-FN scores were statistically similar between both groups, said Dr. Pincus. At 12 and 24 months, the mean MDHAQ-FN improvement from baseline was 40% and 31% in patients in the higher-dose group vs. 34% and 24% in patients in the lower-dose group. The mean improvements in pain scores were also similar between both groups. At 12 and 24 months, the mean improvement in pain from baseline was 37% and 42% in the higher-dose group, and 37% and 35% in the lower-dose group, he said.

When analyzed by 5-year periods, the initial prednisone dose fell from a mean of 10.3 mg in 1980-1984 to 6.5 mg (in 1985-89), 5.1 mg (in 1990-1994), 4.1 mg (in 1995-1999), and 3.6 mg (in 2000-2004). From 1980 to 2004, the median dosage fell from 5 mg/day to 3 mg/day. Before 1990, there were some differences in the pain and function scores between the lower- and higher-dose groups, but the differences were not maintained in the analysis of the 25-year period, he said.

“The findings suggest that many [RA] patients can be treated effectively with initial prednisone doses of less than 5 mg/day, achieving pain and function improvements comparable to those seen at higher doses,” said Dr. Pincus.

Dr. Pincus reported having no financial conflicts of interest to disclose.

COPENHAGEN — Prednisone in initial dosages lower than 5 mg/day is as effective as higher doses in rheumatoid arthritis patients, a study has shown.

Although the use of glucocorticoids in RA remains controversial, the drugs continue to play a major role in the treatment of the disease, Dr. Theodore Pincus said at the annual European Congress of Rheumatology. “Textbooks suggest that glucocorticoids should be used in rheumatoid arthritis only for patients with life-threatening complications, or as a bridge therapy until [disease modifying antirheumatic drug] treatment begins to work, yet estimates suggest that they are used by 20%-80% of patients in usual clinical practice.” Therefore, he noted, determining the lowest effective dosage is important.

Toward this end, Dr. Pincus, clinical professor of medicine at New York University and the Hospital for Joint Diseases, New York, and his colleagues retrospectively analyzed the efficacy of prednisone in the usual care of 308 RA patients treated over a 25-year period. Using a database of all patient visits to a weekly academic clinic during 1980-2004, the investigators analyzed all initial prednisone prescriptions and classified patients into those treated with an initial prednisone dosage of 5 mg/day or higher and those treated with an initial dose lower than 5 mg/day. The 5-mg threshold was used because the efficacy of prednisone at 5 mg daily in RA has been documented, according to Dr. Pincus.

Of the 308 patients, 195 were treated with an initial prednisone dose of 5 mg or higher and 113 were treated with an initial dose less than 5 mg. Nearly all of the patients taking prednisone also took DMARDs, primarily methotrexate.

All of the patients in the study completed the MDHAQ-FN (Multidimensional Health Assessment Questionnaire including physical function measures), and a VAS (Visual Analog Scale) pain measure at each visit. The investigators compared the baseline, 12-month, and 24-month follow-up scores of patients in both dosage groups and used the change in scores from baseline to 12 and 24 months as outcome measures. They also analyzed the data based on 5-year subgroups to account for changes in prescribing practices over time. At baseline, patients in the higher-dose group had higher function and pain scores than did those in the lower-dose group, Dr. Pincus noted in a poster presentation.

The mean improvements in MDHAQ-FN scores were statistically similar between both groups, said Dr. Pincus. At 12 and 24 months, the mean MDHAQ-FN improvement from baseline was 40% and 31% in patients in the higher-dose group vs. 34% and 24% in patients in the lower-dose group. The mean improvements in pain scores were also similar between both groups. At 12 and 24 months, the mean improvement in pain from baseline was 37% and 42% in the higher-dose group, and 37% and 35% in the lower-dose group, he said.

When analyzed by 5-year periods, the initial prednisone dose fell from a mean of 10.3 mg in 1980-1984 to 6.5 mg (in 1985-89), 5.1 mg (in 1990-1994), 4.1 mg (in 1995-1999), and 3.6 mg (in 2000-2004). From 1980 to 2004, the median dosage fell from 5 mg/day to 3 mg/day. Before 1990, there were some differences in the pain and function scores between the lower- and higher-dose groups, but the differences were not maintained in the analysis of the 25-year period, he said.

“The findings suggest that many [RA] patients can be treated effectively with initial prednisone doses of less than 5 mg/day, achieving pain and function improvements comparable to those seen at higher doses,” said Dr. Pincus.

Dr. Pincus reported having no financial conflicts of interest to disclose.

COPENHAGEN — Prednisone in initial dosages lower than 5 mg/day is as effective as higher doses in rheumatoid arthritis patients, a study has shown.

Although the use of glucocorticoids in RA remains controversial, the drugs continue to play a major role in the treatment of the disease, Dr. Theodore Pincus said at the annual European Congress of Rheumatology. “Textbooks suggest that glucocorticoids should be used in rheumatoid arthritis only for patients with life-threatening complications, or as a bridge therapy until [disease modifying antirheumatic drug] treatment begins to work, yet estimates suggest that they are used by 20%-80% of patients in usual clinical practice.” Therefore, he noted, determining the lowest effective dosage is important.

Toward this end, Dr. Pincus, clinical professor of medicine at New York University and the Hospital for Joint Diseases, New York, and his colleagues retrospectively analyzed the efficacy of prednisone in the usual care of 308 RA patients treated over a 25-year period. Using a database of all patient visits to a weekly academic clinic during 1980-2004, the investigators analyzed all initial prednisone prescriptions and classified patients into those treated with an initial prednisone dosage of 5 mg/day or higher and those treated with an initial dose lower than 5 mg/day. The 5-mg threshold was used because the efficacy of prednisone at 5 mg daily in RA has been documented, according to Dr. Pincus.

Of the 308 patients, 195 were treated with an initial prednisone dose of 5 mg or higher and 113 were treated with an initial dose less than 5 mg. Nearly all of the patients taking prednisone also took DMARDs, primarily methotrexate.

All of the patients in the study completed the MDHAQ-FN (Multidimensional Health Assessment Questionnaire including physical function measures), and a VAS (Visual Analog Scale) pain measure at each visit. The investigators compared the baseline, 12-month, and 24-month follow-up scores of patients in both dosage groups and used the change in scores from baseline to 12 and 24 months as outcome measures. They also analyzed the data based on 5-year subgroups to account for changes in prescribing practices over time. At baseline, patients in the higher-dose group had higher function and pain scores than did those in the lower-dose group, Dr. Pincus noted in a poster presentation.

The mean improvements in MDHAQ-FN scores were statistically similar between both groups, said Dr. Pincus. At 12 and 24 months, the mean MDHAQ-FN improvement from baseline was 40% and 31% in patients in the higher-dose group vs. 34% and 24% in patients in the lower-dose group. The mean improvements in pain scores were also similar between both groups. At 12 and 24 months, the mean improvement in pain from baseline was 37% and 42% in the higher-dose group, and 37% and 35% in the lower-dose group, he said.

When analyzed by 5-year periods, the initial prednisone dose fell from a mean of 10.3 mg in 1980-1984 to 6.5 mg (in 1985-89), 5.1 mg (in 1990-1994), 4.1 mg (in 1995-1999), and 3.6 mg (in 2000-2004). From 1980 to 2004, the median dosage fell from 5 mg/day to 3 mg/day. Before 1990, there were some differences in the pain and function scores between the lower- and higher-dose groups, but the differences were not maintained in the analysis of the 25-year period, he said.

“The findings suggest that many [RA] patients can be treated effectively with initial prednisone doses of less than 5 mg/day, achieving pain and function improvements comparable to those seen at higher doses,” said Dr. Pincus.

Dr. Pincus reported having no financial conflicts of interest to disclose.

COPENHAGEN — Prednisone in initial dosages lower than 5 mg/day is as effective as higher doses in rheumatoid arthritis patients, a study has shown.

Although the use of glucocorticoids in RA remains controversial, the drugs continue to play a major role in the treatment of the disease, Dr. Theodore Pincus said at the annual European Congress of Rheumatology. “Textbooks suggest that glucocorticoids should be used in rheumatoid arthritis only for patients with life-threatening complications, or as a bridge therapy until [disease-modifying antirheumatic drug] treatment begins to work, yet estimates suggest that they are used by 20%-80% of patients in usual clinical practice.” Given this reality, he noted, determining the lowest effective dosage is important.

Dr. Pincus of the division of rheumatology at New York University and the Hospital for Joint Diseases, New York, and his colleagues retrospectively analyzed the efficacy of prednisone in the usual care of 308 RA patients treated over a 25-year period. Using a database of all patient visits to a weekly academic clinic during 1980-2004, the investigators analyzed all initial prednisone prescriptions and classified patients into one of two groups: those treated with an initial prednisone dosage of 5 mg/day or higher, and those treated with an initial dose lower than 5 mg/day. The 5-mg threshold was used because the efficacy of prednisone at 5 mg daily in rheumatoid arthritis has been documented, Dr. Pincus said.

Of 308 patients, 195 were treated with an initial prednisone dose of 5 mg or higher and 113 were treated with an initial dose less than 5 mg. Nearly all of the patients taking prednisone also took DMARDs, primarily methotrexate.

All of the patients in the study completed the MDHAQ-FN (Multidimensional Health Assessment Questionnaire including physical function measures, and a VAS (Visual Analog Scale) pain measure at each visit. The investigators compared the baseline, 12-month, and 24-month follow-up scores of patients in both dosage groups and used the change in scores from baseline to 12 and 24 months as outcome measures. They also analyzed the data based on 5-year subgroups to account for changes in prescribing practices over time. At baseline, patients in the higher-dose group had higher function and pain scores than did those in the lower-dose group.

The mean improvements in MDHAQ-FN scores were statistically similar between both groups, said Dr. Pincus. At 12 and 24 months, respectively, the mean MDHAQ-FN improvement from baseline was 40% and 31% in patients in the higher-dose group, compared with 34% and 24% in patients in the lower-dose group. The mean improvements in pain scores were also similar between both groups. At 12 and 24 months, respectively, the mean improvement in pain from baseline was 37% and 42% in the higher-dose group and 37% and 35% in the lower-dose group, he said.

When analyzed by 5-year periods, the initial prednisone dose fell from a mean of 10.3 mg in 1980-1984 to 6.5 mg (in 1985-1989), 5.1 mg (in 1990-1994), 4.1 mg (in 1995-1999), and 3.6 mg (in 2000-2004), said Dr. Pincus. From 1980 to 2004, the median dosage fell from 5 mg/day to 3 mg/day. Before 1990, there were some differences in the pain and functions scores between the lower- and higher-dose groups, but the differences were not maintained in the analysis of the 25-year period, said Dr. Pincus, who reported no conflicts of interest.

COPENHAGEN — Prednisone in initial dosages lower than 5 mg/day is as effective as higher doses in rheumatoid arthritis patients, a study has shown.

Although the use of glucocorticoids in RA remains controversial, the drugs continue to play a major role in the treatment of the disease, Dr. Theodore Pincus said at the annual European Congress of Rheumatology. “Textbooks suggest that glucocorticoids should be used in rheumatoid arthritis only for patients with life-threatening complications, or as a bridge therapy until [disease-modifying antirheumatic drug] treatment begins to work, yet estimates suggest that they are used by 20%-80% of patients in usual clinical practice.” Given this reality, he noted, determining the lowest effective dosage is important.

Dr. Pincus of the division of rheumatology at New York University and the Hospital for Joint Diseases, New York, and his colleagues retrospectively analyzed the efficacy of prednisone in the usual care of 308 RA patients treated over a 25-year period. Using a database of all patient visits to a weekly academic clinic during 1980-2004, the investigators analyzed all initial prednisone prescriptions and classified patients into one of two groups: those treated with an initial prednisone dosage of 5 mg/day or higher, and those treated with an initial dose lower than 5 mg/day. The 5-mg threshold was used because the efficacy of prednisone at 5 mg daily in rheumatoid arthritis has been documented, Dr. Pincus said.

Of 308 patients, 195 were treated with an initial prednisone dose of 5 mg or higher and 113 were treated with an initial dose less than 5 mg. Nearly all of the patients taking prednisone also took DMARDs, primarily methotrexate.

All of the patients in the study completed the MDHAQ-FN (Multidimensional Health Assessment Questionnaire including physical function measures, and a VAS (Visual Analog Scale) pain measure at each visit. The investigators compared the baseline, 12-month, and 24-month follow-up scores of patients in both dosage groups and used the change in scores from baseline to 12 and 24 months as outcome measures. They also analyzed the data based on 5-year subgroups to account for changes in prescribing practices over time. At baseline, patients in the higher-dose group had higher function and pain scores than did those in the lower-dose group.

The mean improvements in MDHAQ-FN scores were statistically similar between both groups, said Dr. Pincus. At 12 and 24 months, respectively, the mean MDHAQ-FN improvement from baseline was 40% and 31% in patients in the higher-dose group, compared with 34% and 24% in patients in the lower-dose group. The mean improvements in pain scores were also similar between both groups. At 12 and 24 months, respectively, the mean improvement in pain from baseline was 37% and 42% in the higher-dose group and 37% and 35% in the lower-dose group, he said.

When analyzed by 5-year periods, the initial prednisone dose fell from a mean of 10.3 mg in 1980-1984 to 6.5 mg (in 1985-1989), 5.1 mg (in 1990-1994), 4.1 mg (in 1995-1999), and 3.6 mg (in 2000-2004), said Dr. Pincus. From 1980 to 2004, the median dosage fell from 5 mg/day to 3 mg/day. Before 1990, there were some differences in the pain and functions scores between the lower- and higher-dose groups, but the differences were not maintained in the analysis of the 25-year period, said Dr. Pincus, who reported no conflicts of interest.

COPENHAGEN — Prednisone in initial dosages lower than 5 mg/day is as effective as higher doses in rheumatoid arthritis patients, a study has shown.

Although the use of glucocorticoids in RA remains controversial, the drugs continue to play a major role in the treatment of the disease, Dr. Theodore Pincus said at the annual European Congress of Rheumatology. “Textbooks suggest that glucocorticoids should be used in rheumatoid arthritis only for patients with life-threatening complications, or as a bridge therapy until [disease-modifying antirheumatic drug] treatment begins to work, yet estimates suggest that they are used by 20%-80% of patients in usual clinical practice.” Given this reality, he noted, determining the lowest effective dosage is important.

Dr. Pincus of the division of rheumatology at New York University and the Hospital for Joint Diseases, New York, and his colleagues retrospectively analyzed the efficacy of prednisone in the usual care of 308 RA patients treated over a 25-year period. Using a database of all patient visits to a weekly academic clinic during 1980-2004, the investigators analyzed all initial prednisone prescriptions and classified patients into one of two groups: those treated with an initial prednisone dosage of 5 mg/day or higher, and those treated with an initial dose lower than 5 mg/day. The 5-mg threshold was used because the efficacy of prednisone at 5 mg daily in rheumatoid arthritis has been documented, Dr. Pincus said.

Of 308 patients, 195 were treated with an initial prednisone dose of 5 mg or higher and 113 were treated with an initial dose less than 5 mg. Nearly all of the patients taking prednisone also took DMARDs, primarily methotrexate.

All of the patients in the study completed the MDHAQ-FN (Multidimensional Health Assessment Questionnaire including physical function measures, and a VAS (Visual Analog Scale) pain measure at each visit. The investigators compared the baseline, 12-month, and 24-month follow-up scores of patients in both dosage groups and used the change in scores from baseline to 12 and 24 months as outcome measures. They also analyzed the data based on 5-year subgroups to account for changes in prescribing practices over time. At baseline, patients in the higher-dose group had higher function and pain scores than did those in the lower-dose group.

The mean improvements in MDHAQ-FN scores were statistically similar between both groups, said Dr. Pincus. At 12 and 24 months, respectively, the mean MDHAQ-FN improvement from baseline was 40% and 31% in patients in the higher-dose group, compared with 34% and 24% in patients in the lower-dose group. The mean improvements in pain scores were also similar between both groups. At 12 and 24 months, respectively, the mean improvement in pain from baseline was 37% and 42% in the higher-dose group and 37% and 35% in the lower-dose group, he said.

When analyzed by 5-year periods, the initial prednisone dose fell from a mean of 10.3 mg in 1980-1984 to 6.5 mg (in 1985-1989), 5.1 mg (in 1990-1994), 4.1 mg (in 1995-1999), and 3.6 mg (in 2000-2004), said Dr. Pincus. From 1980 to 2004, the median dosage fell from 5 mg/day to 3 mg/day. Before 1990, there were some differences in the pain and functions scores between the lower- and higher-dose groups, but the differences were not maintained in the analysis of the 25-year period, said Dr. Pincus, who reported no conflicts of interest.

COPENHAGEN — New recommendations from the European League Against Rheumatism offer a road map for careful assessment of the multiple organ systems affected by systemic lupus erythematosus.

The EULAR guidelines also distinguish potentially reversible disease activity, disease-related organ damage, and health problems that are unrelated to the disease, Dr. Marta Mosca reported at the annual European Congress of Rheumatology.

The evidence-based recommendations “are designed specifically for use in clinical practice by rheumatologists and other clinicians caring for lupus patients,” said Dr. Mosca a rheumatologist at the University of Pisa, Italy, and lead author of the recommendation paper. They include:

▸ Patient assessment. In addition to routine clinical practice, “the assessment of SLE patients must include an evaluation of disease activity with a validated index at each visit and an annual evaluation of organ damage,” Dr. Mosca said. Additionally, general quality of life—as ascertained by patient history and by a 0-10 visual analog scale, comorbidities, and drug toxicity—should be assessed at each visit.

▸ Cardiovascular risk factors. At the baseline visit, and at least once annually during follow-up, “ask patients about smoking, vascular events, physical activity, their use of oral contraceptives and/or hormonal therapies, and family history,” Dr. Mosca said. Lipid profile and serum glucose measurement should be done at baseline and annually thereafter, as should examination of blood pressure and body mass index or waist circumference. “Dependent on the findings, a patient may require more regular follow-up for specific conditions,” she said.

▸ Other comorbidities. Individuals with lupus are at increased risk for certain comorbidities, particularly osteoporosis, Dr. Mosca said. “Corticosteroid medications can trigger bone loss; disease-associated pain and fatigue can lead to inactivity, further increasing the osteoporosis risk; and bone loss may occur as a direct result of the disease.”

The guidelines recommend assessing all SLE patients for adequate calcium and vitamin D intake, regular exercise, and smoking status. SLE patients should be screened and followed for osteoporosis according to the guidelines for post-menopausal women, for patients on steroids, or for patients on any other drug that may interfere with bone mineral density, she said.

Studies have also shown that SLE patients are at an increased risk for certain cancers, “yet lupus patients tend to undergo screening less often than do individuals in the general population,” possibly because lupus-related concerns may take precedence, Dr. Mosca said. The guidelines recommend cancer screening according to the guidelines for the general population. “It's up to the clinicians who care for these patients to encourage appropriate screening,” she said.

▸ Infection risk. Lupus patients should be screened for HIV based on individual risk factors, and they should be screened for the hepatitis C and the hepatitis B viruses and for tuberculosis according to local guidelines before beginning immunosuppressive therapy, according to the recommendations. During immunosuppressive therapy, selected SLE patients should be tested for cytomegalovirus infection, because it increases the degree of immunosuppression of cell-mediated immunity, Dr. Mosca said. Because of the increased risk of infection in SLE, patients should receive only inactivated pneumococcal and influenzae vaccines, according to CDC guidelines for immunosuppressed patients, “preferably during periods of inactive disease,” she said.

▸ Frequency of assessment. The recommendations suggest patient assessments every 6-12 months for individuals with inactive disease, no organ damage, and no comorbidities. The treating clinician should emphasize prevention at the time of these assessments, she said.

▸ Laboratory assessment. According to the guidelines, baseline laboratory assessment should include testing for antinuclear antibodies (ANA), antiphospholipid (aPL) antibodies, Complement 3 (C3) and Complement 4 (C4), as well as the following autoantibodies: anti-double stranded DNA (anti-dsDNA), anti-Ro, anti-La, and antiribonuclear protein (RNP). Prior to pregnancy, previously negative patients should be re-evaluated for aPL, anti-Ro, and anti-La antibodies. Prior to surgery, transplant, or the initiation of estrogen containing treatments, or in the presence of a new neurologic or vascular event, previously negative patients should be tested for aPL, according to Dr. Mosca. At 6- to 12-month intervals in patients with inactive disease, “we recommend performing a complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine, and urinalysis,” she said. “Monitoring should be tailored to specific treatment drugs, when necessary.”

▸ Mucocutaneous involvement. “Mucocutaneous lesions should be characterized, according to existing classification systems, as to whether they may be lupus-specific, lupus nonspecific, lupus mimickers, or drug related,” Dr. Mosca reported. “All lesions should be assessed for activity and damage using validated indexes.”

▸ Kidney involvement. Monitoring recommendations in this domain depend on kidney status. “Patients with persistently abnormal urinalysis or creatinine should have a urine protein/creatinine ratio or 24-hour proteinuria [test], urine microscopy, renal ultrasound, and be considered for biopsy referral,” Dr. Mosca said. “Patients with established nephropathy should have urine protein/creatinine ratio or 24-hour proteinuria [test], immunological studies [C3, C4, anti-dsDNA], and urine microscopy at least every 3 months for the first 2-3 years; and patients with established chronic kidney disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease.”

▸ Neuropsychological manifestations. Although the rate of neurocognitive impairment in SLE is high, “monitoring neurocognitive status is difficult because there are no standardized assessment tools for this population,” Dr. Mosca said. All SLE patients should be monitored for neuropsychological symptoms using a focused history. Additionally, “cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties; and if there is suspicion of cognitive impairment, the patient should be referred to a specialist for a more detailed assessment,” she said.

▸ Eye assessment. Eye damage in patients with lupus varies from minor problems to severe retinopathy. A small percentage of lupus patients develop scleritis, retinal vasculitis, cotton wool spots at the back of the eyeball, or retinal bleeding and swelling of the optic disc. According to the guidelines, patients on steroids or antimalarial drugs should undergo a baseline eye examination according to standard recommendations. Annual follow-up eye exams are recommended in selected patients taking steroids and those at high risk for eye problems, Dr. Mosca said.

In addition to facilitating good clinical practice, the recommendations for monitoring SLE are expected to “improve the quality control of care for lupus patients and to standardize the collection and comparison of data in observational studies,” Dr. Mosca concluded.

The recommendations, which are expected to be published in the Annals of Rheumatic Disease later this year, were developed by an expert panel using a three-staged consensus approach comprising a discussion of relevant categories, a comprehensive literature review and level of evidence assessment, and the integration of the evidence with expert opinion, Dr. Mosca said.

She reported having no financial conflicts of interest to disclose.

COPENHAGEN — New recommendations from the European League Against Rheumatism offer a road map for careful assessment of the multiple organ systems affected by systemic lupus erythematosus.

The EULAR guidelines also distinguish potentially reversible disease activity, disease-related organ damage, and health problems that are unrelated to the disease, Dr. Marta Mosca reported at the annual European Congress of Rheumatology.

The evidence-based recommendations “are designed specifically for use in clinical practice by rheumatologists and other clinicians caring for lupus patients,” said Dr. Mosca a rheumatologist at the University of Pisa, Italy, and lead author of the recommendation paper. They include:

▸ Patient assessment. In addition to routine clinical practice, “the assessment of SLE patients must include an evaluation of disease activity with a validated index at each visit and an annual evaluation of organ damage,” Dr. Mosca said. Additionally, general quality of life—as ascertained by patient history and by a 0-10 visual analog scale, comorbidities, and drug toxicity—should be assessed at each visit.

▸ Cardiovascular risk factors. At the baseline visit, and at least once annually during follow-up, “ask patients about smoking, vascular events, physical activity, their use of oral contraceptives and/or hormonal therapies, and family history,” Dr. Mosca said. Lipid profile and serum glucose measurement should be done at baseline and annually thereafter, as should examination of blood pressure and body mass index or waist circumference. “Dependent on the findings, a patient may require more regular follow-up for specific conditions,” she said.

▸ Other comorbidities. Individuals with lupus are at increased risk for certain comorbidities, particularly osteoporosis, Dr. Mosca said. “Corticosteroid medications can trigger bone loss; disease-associated pain and fatigue can lead to inactivity, further increasing the osteoporosis risk; and bone loss may occur as a direct result of the disease.”

The guidelines recommend assessing all SLE patients for adequate calcium and vitamin D intake, regular exercise, and smoking status. SLE patients should be screened and followed for osteoporosis according to the guidelines for post-menopausal women, for patients on steroids, or for patients on any other drug that may interfere with bone mineral density, she said.

Studies have also shown that SLE patients are at an increased risk for certain cancers, “yet lupus patients tend to undergo screening less often than do individuals in the general population,” possibly because lupus-related concerns may take precedence, Dr. Mosca said. The guidelines recommend cancer screening according to the guidelines for the general population. “It's up to the clinicians who care for these patients to encourage appropriate screening,” she said.

▸ Infection risk. Lupus patients should be screened for HIV based on individual risk factors, and they should be screened for the hepatitis C and the hepatitis B viruses and for tuberculosis according to local guidelines before beginning immunosuppressive therapy, according to the recommendations. During immunosuppressive therapy, selected SLE patients should be tested for cytomegalovirus infection, because it increases the degree of immunosuppression of cell-mediated immunity, Dr. Mosca said. Because of the increased risk of infection in SLE, patients should receive only inactivated pneumococcal and influenzae vaccines, according to CDC guidelines for immunosuppressed patients, “preferably during periods of inactive disease,” she said.

▸ Frequency of assessment. The recommendations suggest patient assessments every 6-12 months for individuals with inactive disease, no organ damage, and no comorbidities. The treating clinician should emphasize prevention at the time of these assessments, she said.

▸ Laboratory assessment. According to the guidelines, baseline laboratory assessment should include testing for antinuclear antibodies (ANA), antiphospholipid (aPL) antibodies, Complement 3 (C3) and Complement 4 (C4), as well as the following autoantibodies: anti-double stranded DNA (anti-dsDNA), anti-Ro, anti-La, and antiribonuclear protein (RNP). Prior to pregnancy, previously negative patients should be re-evaluated for aPL, anti-Ro, and anti-La antibodies. Prior to surgery, transplant, or the initiation of estrogen containing treatments, or in the presence of a new neurologic or vascular event, previously negative patients should be tested for aPL, according to Dr. Mosca. At 6- to 12-month intervals in patients with inactive disease, “we recommend performing a complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine, and urinalysis,” she said. “Monitoring should be tailored to specific treatment drugs, when necessary.”

▸ Mucocutaneous involvement. “Mucocutaneous lesions should be characterized, according to existing classification systems, as to whether they may be lupus-specific, lupus nonspecific, lupus mimickers, or drug related,” Dr. Mosca reported. “All lesions should be assessed for activity and damage using validated indexes.”

▸ Kidney involvement. Monitoring recommendations in this domain depend on kidney status. “Patients with persistently abnormal urinalysis or creatinine should have a urine protein/creatinine ratio or 24-hour proteinuria [test], urine microscopy, renal ultrasound, and be considered for biopsy referral,” Dr. Mosca said. “Patients with established nephropathy should have urine protein/creatinine ratio or 24-hour proteinuria [test], immunological studies [C3, C4, anti-dsDNA], and urine microscopy at least every 3 months for the first 2-3 years; and patients with established chronic kidney disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease.”

▸ Neuropsychological manifestations. Although the rate of neurocognitive impairment in SLE is high, “monitoring neurocognitive status is difficult because there are no standardized assessment tools for this population,” Dr. Mosca said. All SLE patients should be monitored for neuropsychological symptoms using a focused history. Additionally, “cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties; and if there is suspicion of cognitive impairment, the patient should be referred to a specialist for a more detailed assessment,” she said.

▸ Eye assessment. Eye damage in patients with lupus varies from minor problems to severe retinopathy. A small percentage of lupus patients develop scleritis, retinal vasculitis, cotton wool spots at the back of the eyeball, or retinal bleeding and swelling of the optic disc. According to the guidelines, patients on steroids or antimalarial drugs should undergo a baseline eye examination according to standard recommendations. Annual follow-up eye exams are recommended in selected patients taking steroids and those at high risk for eye problems, Dr. Mosca said.

In addition to facilitating good clinical practice, the recommendations for monitoring SLE are expected to “improve the quality control of care for lupus patients and to standardize the collection and comparison of data in observational studies,” Dr. Mosca concluded.

The recommendations, which are expected to be published in the Annals of Rheumatic Disease later this year, were developed by an expert panel using a three-staged consensus approach comprising a discussion of relevant categories, a comprehensive literature review and level of evidence assessment, and the integration of the evidence with expert opinion, Dr. Mosca said.

She reported having no financial conflicts of interest to disclose.

COPENHAGEN — New recommendations from the European League Against Rheumatism offer a road map for careful assessment of the multiple organ systems affected by systemic lupus erythematosus.

The EULAR guidelines also distinguish potentially reversible disease activity, disease-related organ damage, and health problems that are unrelated to the disease, Dr. Marta Mosca reported at the annual European Congress of Rheumatology.

The evidence-based recommendations “are designed specifically for use in clinical practice by rheumatologists and other clinicians caring for lupus patients,” said Dr. Mosca a rheumatologist at the University of Pisa, Italy, and lead author of the recommendation paper. They include:

▸ Patient assessment. In addition to routine clinical practice, “the assessment of SLE patients must include an evaluation of disease activity with a validated index at each visit and an annual evaluation of organ damage,” Dr. Mosca said. Additionally, general quality of life—as ascertained by patient history and by a 0-10 visual analog scale, comorbidities, and drug toxicity—should be assessed at each visit.

▸ Cardiovascular risk factors. At the baseline visit, and at least once annually during follow-up, “ask patients about smoking, vascular events, physical activity, their use of oral contraceptives and/or hormonal therapies, and family history,” Dr. Mosca said. Lipid profile and serum glucose measurement should be done at baseline and annually thereafter, as should examination of blood pressure and body mass index or waist circumference. “Dependent on the findings, a patient may require more regular follow-up for specific conditions,” she said.

▸ Other comorbidities. Individuals with lupus are at increased risk for certain comorbidities, particularly osteoporosis, Dr. Mosca said. “Corticosteroid medications can trigger bone loss; disease-associated pain and fatigue can lead to inactivity, further increasing the osteoporosis risk; and bone loss may occur as a direct result of the disease.”

The guidelines recommend assessing all SLE patients for adequate calcium and vitamin D intake, regular exercise, and smoking status. SLE patients should be screened and followed for osteoporosis according to the guidelines for post-menopausal women, for patients on steroids, or for patients on any other drug that may interfere with bone mineral density, she said.

Studies have also shown that SLE patients are at an increased risk for certain cancers, “yet lupus patients tend to undergo screening less often than do individuals in the general population,” possibly because lupus-related concerns may take precedence, Dr. Mosca said. The guidelines recommend cancer screening according to the guidelines for the general population. “It's up to the clinicians who care for these patients to encourage appropriate screening,” she said.

▸ Infection risk. Lupus patients should be screened for HIV based on individual risk factors, and they should be screened for the hepatitis C and the hepatitis B viruses and for tuberculosis according to local guidelines before beginning immunosuppressive therapy, according to the recommendations. During immunosuppressive therapy, selected SLE patients should be tested for cytomegalovirus infection, because it increases the degree of immunosuppression of cell-mediated immunity, Dr. Mosca said. Because of the increased risk of infection in SLE, patients should receive only inactivated pneumococcal and influenzae vaccines, according to CDC guidelines for immunosuppressed patients, “preferably during periods of inactive disease,” she said.

▸ Frequency of assessment. The recommendations suggest patient assessments every 6-12 months for individuals with inactive disease, no organ damage, and no comorbidities. The treating clinician should emphasize prevention at the time of these assessments, she said.

▸ Laboratory assessment. According to the guidelines, baseline laboratory assessment should include testing for antinuclear antibodies (ANA), antiphospholipid (aPL) antibodies, Complement 3 (C3) and Complement 4 (C4), as well as the following autoantibodies: anti-double stranded DNA (anti-dsDNA), anti-Ro, anti-La, and antiribonuclear protein (RNP). Prior to pregnancy, previously negative patients should be re-evaluated for aPL, anti-Ro, and anti-La antibodies. Prior to surgery, transplant, or the initiation of estrogen containing treatments, or in the presence of a new neurologic or vascular event, previously negative patients should be tested for aPL, according to Dr. Mosca. At 6- to 12-month intervals in patients with inactive disease, “we recommend performing a complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine, and urinalysis,” she said. “Monitoring should be tailored to specific treatment drugs, when necessary.”

▸ Mucocutaneous involvement. “Mucocutaneous lesions should be characterized, according to existing classification systems, as to whether they may be lupus-specific, lupus nonspecific, lupus mimickers, or drug related,” Dr. Mosca reported. “All lesions should be assessed for activity and damage using validated indexes.”

▸ Kidney involvement. Monitoring recommendations in this domain depend on kidney status. “Patients with persistently abnormal urinalysis or creatinine should have a urine protein/creatinine ratio or 24-hour proteinuria [test], urine microscopy, renal ultrasound, and be considered for biopsy referral,” Dr. Mosca said. “Patients with established nephropathy should have urine protein/creatinine ratio or 24-hour proteinuria [test], immunological studies [C3, C4, anti-dsDNA], and urine microscopy at least every 3 months for the first 2-3 years; and patients with established chronic kidney disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease.”

▸ Neuropsychological manifestations. Although the rate of neurocognitive impairment in SLE is high, “monitoring neurocognitive status is difficult because there are no standardized assessment tools for this population,” Dr. Mosca said. All SLE patients should be monitored for neuropsychological symptoms using a focused history. Additionally, “cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties; and if there is suspicion of cognitive impairment, the patient should be referred to a specialist for a more detailed assessment,” she said.

▸ Eye assessment. Eye damage in patients with lupus varies from minor problems to severe retinopathy. A small percentage of lupus patients develop scleritis, retinal vasculitis, cotton wool spots at the back of the eyeball, or retinal bleeding and swelling of the optic disc. According to the guidelines, patients on steroids or antimalarial drugs should undergo a baseline eye examination according to standard recommendations. Annual follow-up eye exams are recommended in selected patients taking steroids and those at high risk for eye problems, Dr. Mosca said.

In addition to facilitating good clinical practice, the recommendations for monitoring SLE are expected to “improve the quality control of care for lupus patients and to standardize the collection and comparison of data in observational studies,” Dr. Mosca concluded.

The recommendations, which are expected to be published in the Annals of Rheumatic Disease later this year, were developed by an expert panel using a three-staged consensus approach comprising a discussion of relevant categories, a comprehensive literature review and level of evidence assessment, and the integration of the evidence with expert opinion, Dr. Mosca said.

She reported having no financial conflicts of interest to disclose.

BOSTON — Noninvasive fat removal is now technically possible, but media hype of new devices may lead to unrealistic expectations.

"We can absolutely remove fat without breaking the stratum corneum [using the new devices], but it's important to put context to this," Dr. Mathew M. Avram said at the American Academy of Dermatology's Academy 2009 meeting.

"While [the devices] are effective, the technology is truly limited at this point. There is a long and deserved reputation of snake oil salesmanship in the field of fat, so it is essential that we assess the new tools critically," said Dr. Avram of Harvard Medical School and Massachusetts General Hospital, Boston.

Focused ultrasound, high-intensity focused ultrasound, radiofrequency, and, most recently, cryolipolysis have shown promise as nonsurgical options for trimming fat from the hips, thighs, abdomen, and buttocks, but they are limited in what they can achieve, said Dr. Avram.

Focused ultrasound, for example, uses mechanical energy to target subcutaneous adipose tissue and break up fat cells, which are then flushed out through the liver, he said.

Clinical studies of patients treated with focused ultrasound, which has not yet received FDA approval for this indication, have demonstrated circumference reductions of 2–3 cm at the thighs, flanks, and abdomen with no associated lipid or liver function abnormalities after three treatments.

"The findings are limited, however, because none of the studies used an untreated control group for comparison and all relied on change in circumference as an outcome measure, which is an imprecise measure of improvement. To truly show a reduction in the fat layer, you really need to use MRI, which is expensive, or high-resolution ultrasound—neither of which were done in these studies." The commercial device that uses this technology is used around the world except in the United States, he said.

High-intensity focused ultrasound devices similarly target and ablate subcutaneous fat while leaving the epidermis, dermis, and surrounding tissue unharmed, but they do so by inducing thermal versus mechanical fat injury, said Dr. Avram.

The efficacy of this method of body contouring, which has also not yet received FDA approval, has yet to be demonstrated in clinical studies.

Unipolar and bipolar radiofrequency-based, nonsurgical skin tightening devices, which many clinicians use for "nonsurgical facelift," are also being used to remove localized fat deposits. These devices, which are cleared by the FDA, deliver radiofrequency energy, and sometimes infrared light energy, into fat deposits over multiple weeks to destroy the fat cell membranes and release the fatty acids for removal through the liver, said Dr. Avram. Although the devices are being used and marketed for fat removal, "at this point we're still awaiting studies to determine the efficacy of the technology."

The latest contender to enter the fat-removal ring is a concept known as cryolipolysis, developed at Massachusetts General Hospital, which cools fat to selectively cause cell breakdown without damaging the surrounding tissue ("Cryolipolysis on Track to Become First Cool Way to Remove Cellulite," April 2009, p. 11).

"The technology is based on the concept of cold panniculitis, or popsicle panniculitis, through which cold exposure causes clinically [and histologically] evident inflammation in fat. The inflammation peaks several days or weeks after the exposure with subsequent focal lipoatrophy," said Dr. Avram.

"What we believe is happening is a selective crystallization in lipids in fat cells at temperatures above freezing—in other words there is a different melting point for fat cells than for the [surrounding tissue]—and there is fat cell apoptosis, followed by slow dissolution of the cell with gradual release of lipids over a period of 2–6 weeks," he said.

The technology, which has not received FDA clearance, has shown promise in an initial human study, said Dr. Avram.

The multicenter investigation included 32 male and female subjects with visible fat on the flank (love handles) or back. The patients were treated using a prototype cryolipolysis device on one side with exposure times ranging from 30 to 45 minutes, while the contralateral side served as the untreated control. Outcome measures included fat-layer reduction as measured by ultrasound, comparison of pre- and posttreatment photographs, and physician assessment.

"At 4 months post treatment, a visible contour change was observed in most of the subjects," said Dr. Avram. Specifically, he noted, ultrasound measurements taken on a subset of 10 subjects demonstrated a fat layer reduction in all; the average reduction was 22.4%.

Among the treatment-related side effects, some of the patients experienced redness at the treatment site that lasted for minutes to hours, as well as bruising and dulling of sensation in the treatment area that resolved within 1–8 weeks, Dr. Avram said, noting that "there were no pigmentary changes, nor were there any lab abnormalities suggesting systemic side effects."

Further studies are needed to establish optimal treatment parameters, but these early results suggest that cryolipolysis will likely be best suited for localized fat removal in areas that are particularly resistant to exercise, he said.

Despite the apparent promise of the new technologies, Dr. Avram was quick to stress that the "clear but limited noninvasive fat removal achieved with these devices is in no way, shape, or form a competitor for liposuction." They are noninvasive alternatives that can achieve certain results, which should be made clear to patients.

Dr. Avram has conducted research for Candela Corp. and owns stock options in Zeltiq Aesthetics, which holds the cryolipolysis patent.

BOSTON — Noninvasive fat removal is now technically possible, but media hype of new devices may lead to unrealistic expectations.

"We can absolutely remove fat without breaking the stratum corneum [using the new devices], but it's important to put context to this," Dr. Mathew M. Avram said at the American Academy of Dermatology's Academy 2009 meeting.

"While [the devices] are effective, the technology is truly limited at this point. There is a long and deserved reputation of snake oil salesmanship in the field of fat, so it is essential that we assess the new tools critically," said Dr. Avram of Harvard Medical School and Massachusetts General Hospital, Boston.

Focused ultrasound, high-intensity focused ultrasound, radiofrequency, and, most recently, cryolipolysis have shown promise as nonsurgical options for trimming fat from the hips, thighs, abdomen, and buttocks, but they are limited in what they can achieve, said Dr. Avram.

Focused ultrasound, for example, uses mechanical energy to target subcutaneous adipose tissue and break up fat cells, which are then flushed out through the liver, he said.

Clinical studies of patients treated with focused ultrasound, which has not yet received FDA approval for this indication, have demonstrated circumference reductions of 2–3 cm at the thighs, flanks, and abdomen with no associated lipid or liver function abnormalities after three treatments.

"The findings are limited, however, because none of the studies used an untreated control group for comparison and all relied on change in circumference as an outcome measure, which is an imprecise measure of improvement. To truly show a reduction in the fat layer, you really need to use MRI, which is expensive, or high-resolution ultrasound—neither of which were done in these studies." The commercial device that uses this technology is used around the world except in the United States, he said.

High-intensity focused ultrasound devices similarly target and ablate subcutaneous fat while leaving the epidermis, dermis, and surrounding tissue unharmed, but they do so by inducing thermal versus mechanical fat injury, said Dr. Avram.

The efficacy of this method of body contouring, which has also not yet received FDA approval, has yet to be demonstrated in clinical studies.

Unipolar and bipolar radiofrequency-based, nonsurgical skin tightening devices, which many clinicians use for "nonsurgical facelift," are also being used to remove localized fat deposits. These devices, which are cleared by the FDA, deliver radiofrequency energy, and sometimes infrared light energy, into fat deposits over multiple weeks to destroy the fat cell membranes and release the fatty acids for removal through the liver, said Dr. Avram. Although the devices are being used and marketed for fat removal, "at this point we're still awaiting studies to determine the efficacy of the technology."

The latest contender to enter the fat-removal ring is a concept known as cryolipolysis, developed at Massachusetts General Hospital, which cools fat to selectively cause cell breakdown without damaging the surrounding tissue ("Cryolipolysis on Track to Become First Cool Way to Remove Cellulite," April 2009, p. 11).

"The technology is based on the concept of cold panniculitis, or popsicle panniculitis, through which cold exposure causes clinically [and histologically] evident inflammation in fat. The inflammation peaks several days or weeks after the exposure with subsequent focal lipoatrophy," said Dr. Avram.

"What we believe is happening is a selective crystallization in lipids in fat cells at temperatures above freezing—in other words there is a different melting point for fat cells than for the [surrounding tissue]—and there is fat cell apoptosis, followed by slow dissolution of the cell with gradual release of lipids over a period of 2–6 weeks," he said.

The technology, which has not received FDA clearance, has shown promise in an initial human study, said Dr. Avram.

The multicenter investigation included 32 male and female subjects with visible fat on the flank (love handles) or back. The patients were treated using a prototype cryolipolysis device on one side with exposure times ranging from 30 to 45 minutes, while the contralateral side served as the untreated control. Outcome measures included fat-layer reduction as measured by ultrasound, comparison of pre- and posttreatment photographs, and physician assessment.

"At 4 months post treatment, a visible contour change was observed in most of the subjects," said Dr. Avram. Specifically, he noted, ultrasound measurements taken on a subset of 10 subjects demonstrated a fat layer reduction in all; the average reduction was 22.4%.

Among the treatment-related side effects, some of the patients experienced redness at the treatment site that lasted for minutes to hours, as well as bruising and dulling of sensation in the treatment area that resolved within 1–8 weeks, Dr. Avram said, noting that "there were no pigmentary changes, nor were there any lab abnormalities suggesting systemic side effects."

Further studies are needed to establish optimal treatment parameters, but these early results suggest that cryolipolysis will likely be best suited for localized fat removal in areas that are particularly resistant to exercise, he said.

Despite the apparent promise of the new technologies, Dr. Avram was quick to stress that the "clear but limited noninvasive fat removal achieved with these devices is in no way, shape, or form a competitor for liposuction." They are noninvasive alternatives that can achieve certain results, which should be made clear to patients.

Dr. Avram has conducted research for Candela Corp. and owns stock options in Zeltiq Aesthetics, which holds the cryolipolysis patent.

BOSTON — Noninvasive fat removal is now technically possible, but media hype of new devices may lead to unrealistic expectations.

"We can absolutely remove fat without breaking the stratum corneum [using the new devices], but it's important to put context to this," Dr. Mathew M. Avram said at the American Academy of Dermatology's Academy 2009 meeting.

"While [the devices] are effective, the technology is truly limited at this point. There is a long and deserved reputation of snake oil salesmanship in the field of fat, so it is essential that we assess the new tools critically," said Dr. Avram of Harvard Medical School and Massachusetts General Hospital, Boston.

Focused ultrasound, high-intensity focused ultrasound, radiofrequency, and, most recently, cryolipolysis have shown promise as nonsurgical options for trimming fat from the hips, thighs, abdomen, and buttocks, but they are limited in what they can achieve, said Dr. Avram.

Focused ultrasound, for example, uses mechanical energy to target subcutaneous adipose tissue and break up fat cells, which are then flushed out through the liver, he said.

Clinical studies of patients treated with focused ultrasound, which has not yet received FDA approval for this indication, have demonstrated circumference reductions of 2–3 cm at the thighs, flanks, and abdomen with no associated lipid or liver function abnormalities after three treatments.

"The findings are limited, however, because none of the studies used an untreated control group for comparison and all relied on change in circumference as an outcome measure, which is an imprecise measure of improvement. To truly show a reduction in the fat layer, you really need to use MRI, which is expensive, or high-resolution ultrasound—neither of which were done in these studies." The commercial device that uses this technology is used around the world except in the United States, he said.

High-intensity focused ultrasound devices similarly target and ablate subcutaneous fat while leaving the epidermis, dermis, and surrounding tissue unharmed, but they do so by inducing thermal versus mechanical fat injury, said Dr. Avram.

The efficacy of this method of body contouring, which has also not yet received FDA approval, has yet to be demonstrated in clinical studies.

Unipolar and bipolar radiofrequency-based, nonsurgical skin tightening devices, which many clinicians use for "nonsurgical facelift," are also being used to remove localized fat deposits. These devices, which are cleared by the FDA, deliver radiofrequency energy, and sometimes infrared light energy, into fat deposits over multiple weeks to destroy the fat cell membranes and release the fatty acids for removal through the liver, said Dr. Avram. Although the devices are being used and marketed for fat removal, "at this point we're still awaiting studies to determine the efficacy of the technology."

The latest contender to enter the fat-removal ring is a concept known as cryolipolysis, developed at Massachusetts General Hospital, which cools fat to selectively cause cell breakdown without damaging the surrounding tissue ("Cryolipolysis on Track to Become First Cool Way to Remove Cellulite," April 2009, p. 11).

"The technology is based on the concept of cold panniculitis, or popsicle panniculitis, through which cold exposure causes clinically [and histologically] evident inflammation in fat. The inflammation peaks several days or weeks after the exposure with subsequent focal lipoatrophy," said Dr. Avram.

"What we believe is happening is a selective crystallization in lipids in fat cells at temperatures above freezing—in other words there is a different melting point for fat cells than for the [surrounding tissue]—and there is fat cell apoptosis, followed by slow dissolution of the cell with gradual release of lipids over a period of 2–6 weeks," he said.

The technology, which has not received FDA clearance, has shown promise in an initial human study, said Dr. Avram.

The multicenter investigation included 32 male and female subjects with visible fat on the flank (love handles) or back. The patients were treated using a prototype cryolipolysis device on one side with exposure times ranging from 30 to 45 minutes, while the contralateral side served as the untreated control. Outcome measures included fat-layer reduction as measured by ultrasound, comparison of pre- and posttreatment photographs, and physician assessment.

"At 4 months post treatment, a visible contour change was observed in most of the subjects," said Dr. Avram. Specifically, he noted, ultrasound measurements taken on a subset of 10 subjects demonstrated a fat layer reduction in all; the average reduction was 22.4%.

Among the treatment-related side effects, some of the patients experienced redness at the treatment site that lasted for minutes to hours, as well as bruising and dulling of sensation in the treatment area that resolved within 1–8 weeks, Dr. Avram said, noting that "there were no pigmentary changes, nor were there any lab abnormalities suggesting systemic side effects."

Further studies are needed to establish optimal treatment parameters, but these early results suggest that cryolipolysis will likely be best suited for localized fat removal in areas that are particularly resistant to exercise, he said.

Despite the apparent promise of the new technologies, Dr. Avram was quick to stress that the "clear but limited noninvasive fat removal achieved with these devices is in no way, shape, or form a competitor for liposuction." They are noninvasive alternatives that can achieve certain results, which should be made clear to patients.

Dr. Avram has conducted research for Candela Corp. and owns stock options in Zeltiq Aesthetics, which holds the cryolipolysis patent.