Diana Mahoney

Hormone therapy to treat menopause-related symptoms or to reduce the risk of certain disorders in postmenopausal women is associated with a favorable risk-benefit ratio when initiated around the time of menopause, but the benefits diminish as the duration of time since menopause increases and among older women, according to the 2010 position statement published by the North American Menopause Society.

The new document updates the organization's 2008 position statement on the role of estrogen and progestogen hormone therapy (HT) by including consensus recommendations derived from key data published since the earlier statement, the authors wrote, noting that the revised statement includes new sections on ovarian and lung cancer, as well as updates to the sections on breast cancer, cognitive aging and decline, dementia, coronary heart disease, stroke, and discontinuance (Menopause 2010;17:242-55).

“Recent data support the initiation of hormone therapy around the time of menopause” to treat menopause-related vasomotor symptoms, sleep disturbance, vaginal atrophy, dyspareunia, or diminished libido and to reduce the risk of osteoporosis and fractures in some women, the authors wrote.

Specifically, findings from the Women's Health Initiative (WHI) trial of estrogen therapy showed that 0.625 mg/day of oral conjugated estrogen effectively treats menopause-related symptoms with low absolute risks. Similarly, in the WHI trial of combined estrogen-progestogen therapy, most risks were deemed rare—except for stroke, which was above the rare category—based on the criteria of the Council for International Organizations of Medical Sciences, the authors wrote.

They noted, however, that “there is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects.” As such, more research is needed before the risks and benefits of HT can be generalized, and “it cannot be assumed that benefits and risks of [HT] apply to all age ranges and durations of therapy,” they wrote.

The most notable changes in the NAMS 2010 position statement on postmenopausal HT are the two new sections on ovarian cancer and lung cancer, which were not included in the 2008 position statement, as well as the assertion that HT is not recommended in women with a history of endometrial cancer, Dr. Margery L.S. Gass, executive director of NAMS, commented in an interview.

The new statement also reflects the latest research on the effect of age on the risk-benefit ratio of postmenopausal HT. The current understanding that the risk-benefit ratio is greatest among women who start HT close to the time of menopause and decreases with time since menopause should make clinicians and women more comfortable using HT right at the time of menopause and more cautious about using it later in life for the prevention of osteoporosis. Most of the side effects associated with HT become more common with aging, even without the use of HT. Therefore, rather than recommending oral or transdermal estrogen for such problems as vaginal dryness and painful intercourse, a local/topical estrogen should be used, said Dr. Gass, also a consultant to the Cleveland Clinic Center for Specialized Women's Health, Mayfield Heights, Ohio.

Regarding the association between hormone therapy and cancer, the data are conflicting, according to the NAMS statement authors. “Unopposed systemic estrogen therapy in postmenopausal women with an intact uterus is associated with increased endometrial cancer risk related to the [estrogen therapy] dose and duration,” they wrote. Thus, concomitant progestogen is recommended in those who use systemic estrogen therapy, and HT is not recommended for women with a history of endometrial cancer.

With respect to ovarian cancer, most epidemiologic studies show no association or a modest association with HT, but observational trial data suggest an increased ovarian cancer risk, the authors wrote. Based on the available data, “the association between ovarian cancer and hormone therapy beyond 5 years, if any, would fall into the rare or very rare category,” they stated, noting that women with a positive family history or other risk factors for ovarian cancer “should be counseled about this rare association.”

The link between HT and breast cancer also is uncertain. Studies have shown that diagnosis of breast cancer increases with estrogen-progestogen use beyond 3-5 years. However, a reanalysis of WHI data suggested that women who started estrogen-progestogen shortly after menopause experienced an increased breast cancer risk over the next 5 years, while those with a gap of more than 5 years between menopause and treatment did not, the authors explained.

Among breast cancer survivors, estrogen-progestogen therapy has not been proved safe and may be associated with an increased risk of recurrence, as indicated in one randomized, controlled trial that “showed a statistically significant 2.4-fold increase in new breast cancer events,” the authors wrote.

The data on lung cancer are particularly contradictory in that it appears that starting estrogen-progestogen therapy in older women with a history of smoking may promote the growth of existing lung cancers, while “evidence from the WHI and some case-control and cohort studies of hormone therapy in a younger population [less than 60 years] shows some protection against lung cancer,” the authors stated. Although confusing, the findings “reinforce the need to encourage prevention or cessation of smoking and possibly to increase surveillance in older smokers who are current or past users of hormone therapy,” they wrote.

The revised statement also addresses the issues of cognitive impairment and coronary heart disease. It recommends against the use of HT at any age “for the sole or primary indication of preventing cognitive aging or dementia,” noting that it may increase the incidence of dementia when initiated in women who are 65 years or older.

Additionally, HT is not recommended as a sole or main indication for coronary protection in women of any age. When HT is started in recently menopausal women for the treatment of menopause symptoms, there does not appear to be an increased risk for coronary heart disease; however, women who initiate HT more than 10 years beyond menopause are at increased CHD risk, the authors noted.

In all cases, because each woman has a unique risk profile and preferences, “individualization of [hormone] therapy is key to providing health benefits with minimal risks, thereby enhancing quality of life,” the authors wrote. Women should be informed of known risks, with the understanding that “a woman's willingness to accept risks of [HT] will vary depending on her individual situation.”

Overall, “NAMS continues to refine our recommendations and approach to hormone therapy as data from the WHI and other studies continue to emerge,” Dr. Cynthia A. Stuenkel, NAMS president, said in an interview. “While we support the use of hormone therapy for symptomatic women [younger than age 60 years], close to the time of menopause, we remind our readers that there are some risks, though small, and there are some uncertainties remaining regarding short-term and long-term effects of hormone therapy.”

In general, “we strongly advocate for the lowest dose for the shortest time for the individual woman who has been carefully counseled about risks and benefits,” said Dr. Stuenkel, clinical professor of medicine at the University of California, San Diego.

Disclosures: Dr. Gass and Dr. Stuenkel reported having no financial conflicts.

The position statement can be found on the NAMS Web site at www.menopause.org/PSht10.pdf

The biggest changes pertain to ovarian, lung, and endometrial cancer, Dr. Margery L.S. Gass said.

My Take

Individualize Hormone Therapy

In general, the 2010 NAMS position statement on postmenopausal hormone therapy is in line with clinical practice; however, many doctors are not prescribing hormones, even when supported by the science, because of bad publicity and a lack of interest combined with fear of litigation.

It is pretty clear that hormone therapy should be used for patients with a clear indication, and the statement outlines what the relevant indications are.

The data coming from the Women's Health Initiative seem to be reversed on the cardiovascular issue. Some of the subanalyses suggest that hormone therapy is associated with a cardiovascular benefit in women close to the age of menopause, while other studies from the same group suggest that this isn't so. Obviously, the science is evolving, and we are only beginning to understand the mechanism of cardiovascular risks and benefits. Overall, however, the statement is pretty clear that we should not use hormones to prevent cardiovascular disease.

In all cases, the decision to initiate hormone therapy has to be individualized to each patient. There is not a one-size-fits-all solution. The main issue is determining what is the safest drug for a woman at a particular time in her life.

Michelle P. Warren, M.D., is director of the Center for Menopause, Hormonal Disorders, and Women's Health at Columbia University Medical Center in New York.

Hormone therapy to treat menopause-related symptoms or to reduce the risk of certain disorders in postmenopausal women is associated with a favorable risk-benefit ratio when initiated around the time of menopause, but the benefits diminish as the duration of time since menopause increases and among older women, according to the 2010 position statement published by the North American Menopause Society.

The new document updates the organization's 2008 position statement on the role of estrogen and progestogen hormone therapy (HT) by including consensus recommendations derived from key data published since the earlier statement, the authors wrote, noting that the revised statement includes new sections on ovarian and lung cancer, as well as updates to the sections on breast cancer, cognitive aging and decline, dementia, coronary heart disease, stroke, and discontinuance (Menopause 2010;17:242-55).

“Recent data support the initiation of hormone therapy around the time of menopause” to treat menopause-related vasomotor symptoms, sleep disturbance, vaginal atrophy, dyspareunia, or diminished libido and to reduce the risk of osteoporosis and fractures in some women, the authors wrote.

Specifically, findings from the Women's Health Initiative (WHI) trial of estrogen therapy showed that 0.625 mg/day of oral conjugated estrogen effectively treats menopause-related symptoms with low absolute risks. Similarly, in the WHI trial of combined estrogen-progestogen therapy, most risks were deemed rare—except for stroke, which was above the rare category—based on the criteria of the Council for International Organizations of Medical Sciences, the authors wrote.

They noted, however, that “there is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects.” As such, more research is needed before the risks and benefits of HT can be generalized, and “it cannot be assumed that benefits and risks of [HT] apply to all age ranges and durations of therapy,” they wrote.

The most notable changes in the NAMS 2010 position statement on postmenopausal HT are the two new sections on ovarian cancer and lung cancer, which were not included in the 2008 position statement, as well as the assertion that HT is not recommended in women with a history of endometrial cancer, Dr. Margery L.S. Gass, executive director of NAMS, commented in an interview.

The new statement also reflects the latest research on the effect of age on the risk-benefit ratio of postmenopausal HT. The current understanding that the risk-benefit ratio is greatest among women who start HT close to the time of menopause and decreases with time since menopause should make clinicians and women more comfortable using HT right at the time of menopause and more cautious about using it later in life for the prevention of osteoporosis. Most of the side effects associated with HT become more common with aging, even without the use of HT. Therefore, rather than recommending oral or transdermal estrogen for such problems as vaginal dryness and painful intercourse, a local/topical estrogen should be used, said Dr. Gass, also a consultant to the Cleveland Clinic Center for Specialized Women's Health, Mayfield Heights, Ohio.

Regarding the association between hormone therapy and cancer, the data are conflicting, according to the NAMS statement authors. “Unopposed systemic estrogen therapy in postmenopausal women with an intact uterus is associated with increased endometrial cancer risk related to the [estrogen therapy] dose and duration,” they wrote. Thus, concomitant progestogen is recommended in those who use systemic estrogen therapy, and HT is not recommended for women with a history of endometrial cancer.

With respect to ovarian cancer, most epidemiologic studies show no association or a modest association with HT, but observational trial data suggest an increased ovarian cancer risk, the authors wrote. Based on the available data, “the association between ovarian cancer and hormone therapy beyond 5 years, if any, would fall into the rare or very rare category,” they stated, noting that women with a positive family history or other risk factors for ovarian cancer “should be counseled about this rare association.”

The link between HT and breast cancer also is uncertain. Studies have shown that diagnosis of breast cancer increases with estrogen-progestogen use beyond 3-5 years. However, a reanalysis of WHI data suggested that women who started estrogen-progestogen shortly after menopause experienced an increased breast cancer risk over the next 5 years, while those with a gap of more than 5 years between menopause and treatment did not, the authors explained.

Among breast cancer survivors, estrogen-progestogen therapy has not been proved safe and may be associated with an increased risk of recurrence, as indicated in one randomized, controlled trial that “showed a statistically significant 2.4-fold increase in new breast cancer events,” the authors wrote.

The data on lung cancer are particularly contradictory in that it appears that starting estrogen-progestogen therapy in older women with a history of smoking may promote the growth of existing lung cancers, while “evidence from the WHI and some case-control and cohort studies of hormone therapy in a younger population [less than 60 years] shows some protection against lung cancer,” the authors stated. Although confusing, the findings “reinforce the need to encourage prevention or cessation of smoking and possibly to increase surveillance in older smokers who are current or past users of hormone therapy,” they wrote.

The revised statement also addresses the issues of cognitive impairment and coronary heart disease. It recommends against the use of HT at any age “for the sole or primary indication of preventing cognitive aging or dementia,” noting that it may increase the incidence of dementia when initiated in women who are 65 years or older.

Additionally, HT is not recommended as a sole or main indication for coronary protection in women of any age. When HT is started in recently menopausal women for the treatment of menopause symptoms, there does not appear to be an increased risk for coronary heart disease; however, women who initiate HT more than 10 years beyond menopause are at increased CHD risk, the authors noted.

In all cases, because each woman has a unique risk profile and preferences, “individualization of [hormone] therapy is key to providing health benefits with minimal risks, thereby enhancing quality of life,” the authors wrote. Women should be informed of known risks, with the understanding that “a woman's willingness to accept risks of [HT] will vary depending on her individual situation.”

Overall, “NAMS continues to refine our recommendations and approach to hormone therapy as data from the WHI and other studies continue to emerge,” Dr. Cynthia A. Stuenkel, NAMS president, said in an interview. “While we support the use of hormone therapy for symptomatic women [younger than age 60 years], close to the time of menopause, we remind our readers that there are some risks, though small, and there are some uncertainties remaining regarding short-term and long-term effects of hormone therapy.”

In general, “we strongly advocate for the lowest dose for the shortest time for the individual woman who has been carefully counseled about risks and benefits,” said Dr. Stuenkel, clinical professor of medicine at the University of California, San Diego.

Disclosures: Dr. Gass and Dr. Stuenkel reported having no financial conflicts.

The position statement can be found on the NAMS Web site at www.menopause.org/PSht10.pdf

The biggest changes pertain to ovarian, lung, and endometrial cancer, Dr. Margery L.S. Gass said.

My Take

Individualize Hormone Therapy

In general, the 2010 NAMS position statement on postmenopausal hormone therapy is in line with clinical practice; however, many doctors are not prescribing hormones, even when supported by the science, because of bad publicity and a lack of interest combined with fear of litigation.

It is pretty clear that hormone therapy should be used for patients with a clear indication, and the statement outlines what the relevant indications are.

The data coming from the Women's Health Initiative seem to be reversed on the cardiovascular issue. Some of the subanalyses suggest that hormone therapy is associated with a cardiovascular benefit in women close to the age of menopause, while other studies from the same group suggest that this isn't so. Obviously, the science is evolving, and we are only beginning to understand the mechanism of cardiovascular risks and benefits. Overall, however, the statement is pretty clear that we should not use hormones to prevent cardiovascular disease.

In all cases, the decision to initiate hormone therapy has to be individualized to each patient. There is not a one-size-fits-all solution. The main issue is determining what is the safest drug for a woman at a particular time in her life.

Michelle P. Warren, M.D., is director of the Center for Menopause, Hormonal Disorders, and Women's Health at Columbia University Medical Center in New York.

Hormone therapy to treat menopause-related symptoms or to reduce the risk of certain disorders in postmenopausal women is associated with a favorable risk-benefit ratio when initiated around the time of menopause, but the benefits diminish as the duration of time since menopause increases and among older women, according to the 2010 position statement published by the North American Menopause Society.

The new document updates the organization's 2008 position statement on the role of estrogen and progestogen hormone therapy (HT) by including consensus recommendations derived from key data published since the earlier statement, the authors wrote, noting that the revised statement includes new sections on ovarian and lung cancer, as well as updates to the sections on breast cancer, cognitive aging and decline, dementia, coronary heart disease, stroke, and discontinuance (Menopause 2010;17:242-55).

“Recent data support the initiation of hormone therapy around the time of menopause” to treat menopause-related vasomotor symptoms, sleep disturbance, vaginal atrophy, dyspareunia, or diminished libido and to reduce the risk of osteoporosis and fractures in some women, the authors wrote.

Specifically, findings from the Women's Health Initiative (WHI) trial of estrogen therapy showed that 0.625 mg/day of oral conjugated estrogen effectively treats menopause-related symptoms with low absolute risks. Similarly, in the WHI trial of combined estrogen-progestogen therapy, most risks were deemed rare—except for stroke, which was above the rare category—based on the criteria of the Council for International Organizations of Medical Sciences, the authors wrote.

They noted, however, that “there is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects.” As such, more research is needed before the risks and benefits of HT can be generalized, and “it cannot be assumed that benefits and risks of [HT] apply to all age ranges and durations of therapy,” they wrote.

The most notable changes in the NAMS 2010 position statement on postmenopausal HT are the two new sections on ovarian cancer and lung cancer, which were not included in the 2008 position statement, as well as the assertion that HT is not recommended in women with a history of endometrial cancer, Dr. Margery L.S. Gass, executive director of NAMS, commented in an interview.

The new statement also reflects the latest research on the effect of age on the risk-benefit ratio of postmenopausal HT. The current understanding that the risk-benefit ratio is greatest among women who start HT close to the time of menopause and decreases with time since menopause should make clinicians and women more comfortable using HT right at the time of menopause and more cautious about using it later in life for the prevention of osteoporosis. Most of the side effects associated with HT become more common with aging, even without the use of HT. Therefore, rather than recommending oral or transdermal estrogen for such problems as vaginal dryness and painful intercourse, a local/topical estrogen should be used, said Dr. Gass, also a consultant to the Cleveland Clinic Center for Specialized Women's Health, Mayfield Heights, Ohio.

Regarding the association between hormone therapy and cancer, the data are conflicting, according to the NAMS statement authors. “Unopposed systemic estrogen therapy in postmenopausal women with an intact uterus is associated with increased endometrial cancer risk related to the [estrogen therapy] dose and duration,” they wrote. Thus, concomitant progestogen is recommended in those who use systemic estrogen therapy, and HT is not recommended for women with a history of endometrial cancer.

With respect to ovarian cancer, most epidemiologic studies show no association or a modest association with HT, but observational trial data suggest an increased ovarian cancer risk, the authors wrote. Based on the available data, “the association between ovarian cancer and hormone therapy beyond 5 years, if any, would fall into the rare or very rare category,” they stated, noting that women with a positive family history or other risk factors for ovarian cancer “should be counseled about this rare association.”

The link between HT and breast cancer also is uncertain. Studies have shown that diagnosis of breast cancer increases with estrogen-progestogen use beyond 3-5 years. However, a reanalysis of WHI data suggested that women who started estrogen-progestogen shortly after menopause experienced an increased breast cancer risk over the next 5 years, while those with a gap of more than 5 years between menopause and treatment did not, the authors explained.

Among breast cancer survivors, estrogen-progestogen therapy has not been proved safe and may be associated with an increased risk of recurrence, as indicated in one randomized, controlled trial that “showed a statistically significant 2.4-fold increase in new breast cancer events,” the authors wrote.

The data on lung cancer are particularly contradictory in that it appears that starting estrogen-progestogen therapy in older women with a history of smoking may promote the growth of existing lung cancers, while “evidence from the WHI and some case-control and cohort studies of hormone therapy in a younger population [less than 60 years] shows some protection against lung cancer,” the authors stated. Although confusing, the findings “reinforce the need to encourage prevention or cessation of smoking and possibly to increase surveillance in older smokers who are current or past users of hormone therapy,” they wrote.

The revised statement also addresses the issues of cognitive impairment and coronary heart disease. It recommends against the use of HT at any age “for the sole or primary indication of preventing cognitive aging or dementia,” noting that it may increase the incidence of dementia when initiated in women who are 65 years or older.

Additionally, HT is not recommended as a sole or main indication for coronary protection in women of any age. When HT is started in recently menopausal women for the treatment of menopause symptoms, there does not appear to be an increased risk for coronary heart disease; however, women who initiate HT more than 10 years beyond menopause are at increased CHD risk, the authors noted.

In all cases, because each woman has a unique risk profile and preferences, “individualization of [hormone] therapy is key to providing health benefits with minimal risks, thereby enhancing quality of life,” the authors wrote. Women should be informed of known risks, with the understanding that “a woman's willingness to accept risks of [HT] will vary depending on her individual situation.”

Overall, “NAMS continues to refine our recommendations and approach to hormone therapy as data from the WHI and other studies continue to emerge,” Dr. Cynthia A. Stuenkel, NAMS president, said in an interview. “While we support the use of hormone therapy for symptomatic women [younger than age 60 years], close to the time of menopause, we remind our readers that there are some risks, though small, and there are some uncertainties remaining regarding short-term and long-term effects of hormone therapy.”

In general, “we strongly advocate for the lowest dose for the shortest time for the individual woman who has been carefully counseled about risks and benefits,” said Dr. Stuenkel, clinical professor of medicine at the University of California, San Diego.

Disclosures: Dr. Gass and Dr. Stuenkel reported having no financial conflicts.

The position statement can be found on the NAMS Web site at www.menopause.org/PSht10.pdf

The biggest changes pertain to ovarian, lung, and endometrial cancer, Dr. Margery L.S. Gass said.

My Take

Individualize Hormone Therapy

In general, the 2010 NAMS position statement on postmenopausal hormone therapy is in line with clinical practice; however, many doctors are not prescribing hormones, even when supported by the science, because of bad publicity and a lack of interest combined with fear of litigation.

It is pretty clear that hormone therapy should be used for patients with a clear indication, and the statement outlines what the relevant indications are.

The data coming from the Women's Health Initiative seem to be reversed on the cardiovascular issue. Some of the subanalyses suggest that hormone therapy is associated with a cardiovascular benefit in women close to the age of menopause, while other studies from the same group suggest that this isn't so. Obviously, the science is evolving, and we are only beginning to understand the mechanism of cardiovascular risks and benefits. Overall, however, the statement is pretty clear that we should not use hormones to prevent cardiovascular disease.

In all cases, the decision to initiate hormone therapy has to be individualized to each patient. There is not a one-size-fits-all solution. The main issue is determining what is the safest drug for a woman at a particular time in her life.

Michelle P. Warren, M.D., is director of the Center for Menopause, Hormonal Disorders, and Women's Health at Columbia University Medical Center in New York.

WASHINGTON — Despite being a major public health threat, “the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

Fewer than 10% of the unique autoimmune or autoimmune-related diseases have currently available therapies, and new drug development programs target only about 30%, according to a recent report. The costs associated with the seven major autoimmune diseases—Crohn's disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma—are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. The most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that's important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases,” Dr. Daniel Rotrosen said at the summit.

One research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation at the National Institute of Allergy and Infectious Diseases.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease, and one-third for other conditions,” Dr. Rotrosen said, noting that clinical trials in this arena are notoriously difficult. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

Subject recruitment can also be challenging. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, Dr. Rotrosen said. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said.

Disclosures: Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

WASHINGTON — Despite being a major public health threat, “the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

Fewer than 10% of the unique autoimmune or autoimmune-related diseases have currently available therapies, and new drug development programs target only about 30%, according to a recent report. The costs associated with the seven major autoimmune diseases—Crohn's disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma—are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. The most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that's important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases,” Dr. Daniel Rotrosen said at the summit.

One research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation at the National Institute of Allergy and Infectious Diseases.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease, and one-third for other conditions,” Dr. Rotrosen said, noting that clinical trials in this arena are notoriously difficult. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

Subject recruitment can also be challenging. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, Dr. Rotrosen said. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said.

Disclosures: Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

WASHINGTON — Despite being a major public health threat, “the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

Fewer than 10% of the unique autoimmune or autoimmune-related diseases have currently available therapies, and new drug development programs target only about 30%, according to a recent report. The costs associated with the seven major autoimmune diseases—Crohn's disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma—are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. The most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that's important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases,” Dr. Daniel Rotrosen said at the summit.

One research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation at the National Institute of Allergy and Infectious Diseases.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease, and one-third for other conditions,” Dr. Rotrosen said, noting that clinical trials in this arena are notoriously difficult. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

Subject recruitment can also be challenging. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, Dr. Rotrosen said. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said.

Disclosures: Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

Major Finding: Diabetes patients with multimorbidity and their physicians commonly don't agree on the relative importance of comorbid health conditions.

Data Source: Prospective cohort study of 92 primary care providers and 1,169 of their diabetic patients with comorbid hypertension.

Disclosures: The study was supported by the Robert Wood Johnson Clinical Scholars Program. The authors reported having no financial disclosures.

Diabetes patients with multiple health concerns and their physicians are not always on the same page regarding the relative importance of specific comorbidities, and this incongruity could have clinical management implications, according to a report by University of Michigan researchers.

In a prospective cohort study designed to assess concordance of patient and physician priorities, Dr. Donna M. Zulman and her colleagues from the University of Michigan, Ann Arbor, surveyed 92 primary care providers and 1,169 of their diabetic patients, asking the patients to rank their most important health concerns and asking the providers to rank the most important conditions likely to affect the patients' health outcomes.

For 60% of the patient-provider pairs, concordance was high, meaning that the provider ranked the same top three health concerns as the patient or that the provider ranked two of the same health concerns as the patient, and these two matched the patient's most important concerns, the authors reported. For 72% of the patient-provider pairs included in the analysis, the patient's most important concern was on the provider's top three list, but only 16% of the pairs had three matches, 55% had two matches, and 25% had one match, while 4% had no matching health concerns, they wrote (J. Gen. Intern. Med. 2010 Feb. 2 [doi:10.1007/s11606-009-1232-1

The discordance between patient and physician perception of hypertension as the most important comorbidity in diabetic patients was especially notable, according to the authors. “Although providers ranked hypertension as the most important health condition for 384 (38%) patients, only 184 (18%) patients listed hypertension as their most important health concern,” they wrote. “Patients were more likely than providers to list 'losing weight or being more active' in their top three concerns (35% vs. 21%, respectively).” This finding is consistent with previous data suggesting that many diabetic patients are not aware of the importance of blood pressure control despite the available evidence and clinical guidelines that stress its importance, the authors said.

Another striking disconnect was observed between patients who listed pain or depression as their top health concern relative to the number of their providers who ranked these conditions as likely to affect the patient's health outcomes. For example, only 9% of patients who listed pain as their top health concern had a provider who ranked it among the top three, and only 32% of patients who listed depression as their most important comorbidity had physicians who agreed, the authors reported.

“This discordance is concerning, not only because it raises the possibility that providers are unaware of the extent to which these conditions affect their patients, but also because pain and depression can be barriers to effective diabetes self-management, and (in the case of depression) may worsen glycemic control and increase the risk of mortality,” they wrote. “By deemphasizing symptomatic conditions, providers are actually neglecting some of the most important medical concerns that are likely to affect health outcomes in these patients,” they noted.

The study had several limitations, according to the authors. These include the inability of the concordance score to measure the concept of which conditions the providers thought the patients would prioritize. Another was that the patients and providers were aware that the study was looking at diabetic patients with an elevated blood pressure level at triage, thus making it more likely that hypertension and diabetes would be listed among the top three health concerns and potentially hindering the evaluation of concordance patterns among other health conditions.

Overall, the findings suggest the need for improved communication about the risks associated with comorbidities, according to the authors. Additionally, the results “reinforce the need for heightened provider recognition of patients' symptomatic conditions as well as their non-health competing demands,” they wrote, adding that future research should focus on ways to encourage and implement these practices in primary care.

Major Finding: Diabetes patients with multimorbidity and their physicians commonly don't agree on the relative importance of comorbid health conditions.

Data Source: Prospective cohort study of 92 primary care providers and 1,169 of their diabetic patients with comorbid hypertension.

Disclosures: The study was supported by the Robert Wood Johnson Clinical Scholars Program. The authors reported having no financial disclosures.

Diabetes patients with multiple health concerns and their physicians are not always on the same page regarding the relative importance of specific comorbidities, and this incongruity could have clinical management implications, according to a report by University of Michigan researchers.

In a prospective cohort study designed to assess concordance of patient and physician priorities, Dr. Donna M. Zulman and her colleagues from the University of Michigan, Ann Arbor, surveyed 92 primary care providers and 1,169 of their diabetic patients, asking the patients to rank their most important health concerns and asking the providers to rank the most important conditions likely to affect the patients' health outcomes.

For 60% of the patient-provider pairs, concordance was high, meaning that the provider ranked the same top three health concerns as the patient or that the provider ranked two of the same health concerns as the patient, and these two matched the patient's most important concerns, the authors reported. For 72% of the patient-provider pairs included in the analysis, the patient's most important concern was on the provider's top three list, but only 16% of the pairs had three matches, 55% had two matches, and 25% had one match, while 4% had no matching health concerns, they wrote (J. Gen. Intern. Med. 2010 Feb. 2 [doi:10.1007/s11606-009-1232-1

The discordance between patient and physician perception of hypertension as the most important comorbidity in diabetic patients was especially notable, according to the authors. “Although providers ranked hypertension as the most important health condition for 384 (38%) patients, only 184 (18%) patients listed hypertension as their most important health concern,” they wrote. “Patients were more likely than providers to list 'losing weight or being more active' in their top three concerns (35% vs. 21%, respectively).” This finding is consistent with previous data suggesting that many diabetic patients are not aware of the importance of blood pressure control despite the available evidence and clinical guidelines that stress its importance, the authors said.

Another striking disconnect was observed between patients who listed pain or depression as their top health concern relative to the number of their providers who ranked these conditions as likely to affect the patient's health outcomes. For example, only 9% of patients who listed pain as their top health concern had a provider who ranked it among the top three, and only 32% of patients who listed depression as their most important comorbidity had physicians who agreed, the authors reported.

“This discordance is concerning, not only because it raises the possibility that providers are unaware of the extent to which these conditions affect their patients, but also because pain and depression can be barriers to effective diabetes self-management, and (in the case of depression) may worsen glycemic control and increase the risk of mortality,” they wrote. “By deemphasizing symptomatic conditions, providers are actually neglecting some of the most important medical concerns that are likely to affect health outcomes in these patients,” they noted.

The study had several limitations, according to the authors. These include the inability of the concordance score to measure the concept of which conditions the providers thought the patients would prioritize. Another was that the patients and providers were aware that the study was looking at diabetic patients with an elevated blood pressure level at triage, thus making it more likely that hypertension and diabetes would be listed among the top three health concerns and potentially hindering the evaluation of concordance patterns among other health conditions.

Overall, the findings suggest the need for improved communication about the risks associated with comorbidities, according to the authors. Additionally, the results “reinforce the need for heightened provider recognition of patients' symptomatic conditions as well as their non-health competing demands,” they wrote, adding that future research should focus on ways to encourage and implement these practices in primary care.

Major Finding: Diabetes patients with multimorbidity and their physicians commonly don't agree on the relative importance of comorbid health conditions.

Data Source: Prospective cohort study of 92 primary care providers and 1,169 of their diabetic patients with comorbid hypertension.

Disclosures: The study was supported by the Robert Wood Johnson Clinical Scholars Program. The authors reported having no financial disclosures.

Diabetes patients with multiple health concerns and their physicians are not always on the same page regarding the relative importance of specific comorbidities, and this incongruity could have clinical management implications, according to a report by University of Michigan researchers.

In a prospective cohort study designed to assess concordance of patient and physician priorities, Dr. Donna M. Zulman and her colleagues from the University of Michigan, Ann Arbor, surveyed 92 primary care providers and 1,169 of their diabetic patients, asking the patients to rank their most important health concerns and asking the providers to rank the most important conditions likely to affect the patients' health outcomes.

For 60% of the patient-provider pairs, concordance was high, meaning that the provider ranked the same top three health concerns as the patient or that the provider ranked two of the same health concerns as the patient, and these two matched the patient's most important concerns, the authors reported. For 72% of the patient-provider pairs included in the analysis, the patient's most important concern was on the provider's top three list, but only 16% of the pairs had three matches, 55% had two matches, and 25% had one match, while 4% had no matching health concerns, they wrote (J. Gen. Intern. Med. 2010 Feb. 2 [doi:10.1007/s11606-009-1232-1

The discordance between patient and physician perception of hypertension as the most important comorbidity in diabetic patients was especially notable, according to the authors. “Although providers ranked hypertension as the most important health condition for 384 (38%) patients, only 184 (18%) patients listed hypertension as their most important health concern,” they wrote. “Patients were more likely than providers to list 'losing weight or being more active' in their top three concerns (35% vs. 21%, respectively).” This finding is consistent with previous data suggesting that many diabetic patients are not aware of the importance of blood pressure control despite the available evidence and clinical guidelines that stress its importance, the authors said.

Another striking disconnect was observed between patients who listed pain or depression as their top health concern relative to the number of their providers who ranked these conditions as likely to affect the patient's health outcomes. For example, only 9% of patients who listed pain as their top health concern had a provider who ranked it among the top three, and only 32% of patients who listed depression as their most important comorbidity had physicians who agreed, the authors reported.

“This discordance is concerning, not only because it raises the possibility that providers are unaware of the extent to which these conditions affect their patients, but also because pain and depression can be barriers to effective diabetes self-management, and (in the case of depression) may worsen glycemic control and increase the risk of mortality,” they wrote. “By deemphasizing symptomatic conditions, providers are actually neglecting some of the most important medical concerns that are likely to affect health outcomes in these patients,” they noted.

The study had several limitations, according to the authors. These include the inability of the concordance score to measure the concept of which conditions the providers thought the patients would prioritize. Another was that the patients and providers were aware that the study was looking at diabetic patients with an elevated blood pressure level at triage, thus making it more likely that hypertension and diabetes would be listed among the top three health concerns and potentially hindering the evaluation of concordance patterns among other health conditions.

Overall, the findings suggest the need for improved communication about the risks associated with comorbidities, according to the authors. Additionally, the results “reinforce the need for heightened provider recognition of patients' symptomatic conditions as well as their non-health competing demands,” they wrote, adding that future research should focus on ways to encourage and implement these practices in primary care.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains from 1-17, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact. Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated. “The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more comprehensive validated instrument or questionnaire. Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote. “In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

In addition to enabling the assessment of all of the domains of major importance to patients, the patient-derived measure has the benefit of being “easy to fill in and score,” making it a practical research tool, Dr. Gossec said. Although the score is less sensitive to change than the Disease Activity Score–28, “so are all patient-reported outcomes,” she noted.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec, noting that “preliminary results indicate it is a valid assessment of the patients' perspective in rheumatoid arthritis.”

Dr. Tore K. Kvien said in an interview that additional validation studies are needed to assess the psychometric properties of the RAID score, to finalize the choice of domains and instruments, and to compare its value to that of existing patient-reported outcome indices. However, “the measure will become an important tool for both research and clinical practice in the future because of its ability to capture information that is relevant for patients,” said Dr. Kvien, a principal investigator and professor of rheumatology at the University of Oslo. In particular, it will provide researchers and clinicians with a more thorough picture of the patient experience when measuring the efficacy of disease interventions, he said.

Disclosures: Dr. Gossec, Dr. Kvien, and the study coauthors reported having no financial conflicts of interest.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains from 1-17, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact. Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated. “The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more comprehensive validated instrument or questionnaire. Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote. “In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

In addition to enabling the assessment of all of the domains of major importance to patients, the patient-derived measure has the benefit of being “easy to fill in and score,” making it a practical research tool, Dr. Gossec said. Although the score is less sensitive to change than the Disease Activity Score–28, “so are all patient-reported outcomes,” she noted.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec, noting that “preliminary results indicate it is a valid assessment of the patients' perspective in rheumatoid arthritis.”

Dr. Tore K. Kvien said in an interview that additional validation studies are needed to assess the psychometric properties of the RAID score, to finalize the choice of domains and instruments, and to compare its value to that of existing patient-reported outcome indices. However, “the measure will become an important tool for both research and clinical practice in the future because of its ability to capture information that is relevant for patients,” said Dr. Kvien, a principal investigator and professor of rheumatology at the University of Oslo. In particular, it will provide researchers and clinicians with a more thorough picture of the patient experience when measuring the efficacy of disease interventions, he said.

Disclosures: Dr. Gossec, Dr. Kvien, and the study coauthors reported having no financial conflicts of interest.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains from 1-17, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact. Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated. “The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more comprehensive validated instrument or questionnaire. Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote. “In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

In addition to enabling the assessment of all of the domains of major importance to patients, the patient-derived measure has the benefit of being “easy to fill in and score,” making it a practical research tool, Dr. Gossec said. Although the score is less sensitive to change than the Disease Activity Score–28, “so are all patient-reported outcomes,” she noted.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec, noting that “preliminary results indicate it is a valid assessment of the patients' perspective in rheumatoid arthritis.”

Dr. Tore K. Kvien said in an interview that additional validation studies are needed to assess the psychometric properties of the RAID score, to finalize the choice of domains and instruments, and to compare its value to that of existing patient-reported outcome indices. However, “the measure will become an important tool for both research and clinical practice in the future because of its ability to capture information that is relevant for patients,” said Dr. Kvien, a principal investigator and professor of rheumatology at the University of Oslo. In particular, it will provide researchers and clinicians with a more thorough picture of the patient experience when measuring the efficacy of disease interventions, he said.

Disclosures: Dr. Gossec, Dr. Kvien, and the study coauthors reported having no financial conflicts of interest.

Major Finding: Seizure frequency declined by a mean of 29% during active stimulation with the device over the first 12 weeks, compared with a 14% reduction during sham activation.

Data Source: Multicenter, randomized, sham-controlled clinical trial of 191 patients with medically intractable, partial onset seizures.

Disclosures: Dr. Morrell is the chief medical officer of NeuroPace, which developed the system and funded the trial.

BOSTON — Patients with treatment-resistant epilepsy can reduce seizure frequency with the use of an implantable device that detects preseizure electrical activity and aborts seizures, the results of a multicenter, randomized trial suggest.

In 191 patients with medically intractable, partial onset seizures who were implanted with the neurostimulator, seizures declined by a mean of 29% during active stimulation with the device, compared with a 14% reduction during sham activation, Dr. Martha J. Morrell reported at the annual meeting of the American Epilepsy Society.

In the later, open-label phase of the study in which all patients received active stimulation, nearly half of the 171 patients for whom 12 weeks of data were available had at least a 50% reduction in seizure frequency relative to baseline, said Dr. Morrell, clinical professor of neurology at Stanford (Calif.) University and chief medical officer of NeuroPace, developer of the Responsive Neurostimulator System (RNS).

The cranially implanted RNS device differs from conventional, “open loop” brain stimulation technologies that involve the scheduled delivery of electrical stimulation to specific brain regions independent of brain activity.

“The RNS delivers stimulation in response to a detected event,” Dr. Morrell said. The “individualized and dynamic” treatment responds to patterns of brain activity specific to a patient's seizure pattern. The electrodes are implanted in epileptic regions of the brain and connected to the battery-powered neurostimulator embedded in the skull.

“The programming is done wirelessly by the physician via a laptop computer,” Dr. Morrell said. “It's highly modifiable in that the physician can view the patient's electrocorticographic activity in real-time and change the [signal-detection] criteria at any time based on individual patient characteristics.”

Up to two leads, each containing four electrodes, can be connected to the neurostimulator, so the system can monitor and stimulate two distinct epileptogenic zones independently, she noted.

Because the neurostimulation occurs in response to aberrant electrical activity, fewer electrical impulses are delivered than would occur with continuous stimulation. This diminishes the risk of treatment-related adverse events, Dr. Morrell explained.

In an initial feasibility study of 65 patients, the responsive neurostimulation system demonstrated excellent safety, tolerability, and preliminary evidence of efficacy, Dr. Morrell said. “There were no serious device-related adverse events, and stimulation-related symptoms experienced by several subjects were addressed by adjusting the stimulation settings.”

A minimum 50% reduction in seizure frequency was achieved in 43% of the patients with complex partial seizures and 35% of those with total disabling seizures (Neurotherapeutics 2008;5:68-74).

In the double-blind pivotal trial, the 191 patients were randomized to active or sham therapy. All were 18-70 years of age (median 35 years), and all had partial onset epilepsy localized to one or two foci and had failed at least two antiepileptic medications.

The patients were taking an average of three antiepileptic medications to attempt seizure control; 34% had been treated previously with vagus nerve stimulation, 33% had prior surgical resection, and 16% had been treated with both.

“These patients tended to be very ill. Most of them had epilepsy for more than 20 years, and many were having at least three seizures per 28-day period—often many more than that,” Dr. Morrell said.

Of the 191 patients implanted with the device, 50% had mesial temporal seizure onset, 42% had neocortical seizure onset, and 8% had both, Dr. Morrell said at a press briefing during the meeting.

An initial, 12-week period prior to system implantation, during which baseline seizure activity was collected, was followed by a 12-week blinded period when participants were randomly assigned to have the responsive stimulation activated or left inactive, she said.

At each of the 31 trial sites, the patients and one neurologist were blinded to stimulation status, while a separate neurologist programmed the devices in order to maintain the study blinding. The responsive stimulation was optimized in the treatment over the next 4 weeks, followed by 84 days of data collection. At the end of the blinded efficacy period, stimulation was activated for all of the study participants for 2 years.

There were no serious, unanticipated device-related adverse events during the trial, nor was there a difference between the two groups with respect to the rate of adverse events, including depression, memory impairment, and anxiety, Dr. Morrell reported.

The findings suggest that responsive neurostimulation might be a promising treatment option for patients with seizures that are resistant to conventional antiepileptic therapy. The apparent increase in the number of patients experiencing at least a 50% reduction in seizure frequency relative to baseline during the open-label phase of the study suggests the system might become more effective over time, she noted.

The system has not yet received Food and Drug Administration approval, but NeuroPace plans to submit a premarket approval application to the FDA in early 2010, Dr. Morrell said.

Major Finding: Seizure frequency declined by a mean of 29% during active stimulation with the device over the first 12 weeks, compared with a 14% reduction during sham activation.

Data Source: Multicenter, randomized, sham-controlled clinical trial of 191 patients with medically intractable, partial onset seizures.

Disclosures: Dr. Morrell is the chief medical officer of NeuroPace, which developed the system and funded the trial.

BOSTON — Patients with treatment-resistant epilepsy can reduce seizure frequency with the use of an implantable device that detects preseizure electrical activity and aborts seizures, the results of a multicenter, randomized trial suggest.

In 191 patients with medically intractable, partial onset seizures who were implanted with the neurostimulator, seizures declined by a mean of 29% during active stimulation with the device, compared with a 14% reduction during sham activation, Dr. Martha J. Morrell reported at the annual meeting of the American Epilepsy Society.

In the later, open-label phase of the study in which all patients received active stimulation, nearly half of the 171 patients for whom 12 weeks of data were available had at least a 50% reduction in seizure frequency relative to baseline, said Dr. Morrell, clinical professor of neurology at Stanford (Calif.) University and chief medical officer of NeuroPace, developer of the Responsive Neurostimulator System (RNS).

The cranially implanted RNS device differs from conventional, “open loop” brain stimulation technologies that involve the scheduled delivery of electrical stimulation to specific brain regions independent of brain activity.

“The RNS delivers stimulation in response to a detected event,” Dr. Morrell said. The “individualized and dynamic” treatment responds to patterns of brain activity specific to a patient's seizure pattern. The electrodes are implanted in epileptic regions of the brain and connected to the battery-powered neurostimulator embedded in the skull.

“The programming is done wirelessly by the physician via a laptop computer,” Dr. Morrell said. “It's highly modifiable in that the physician can view the patient's electrocorticographic activity in real-time and change the [signal-detection] criteria at any time based on individual patient characteristics.”

Up to two leads, each containing four electrodes, can be connected to the neurostimulator, so the system can monitor and stimulate two distinct epileptogenic zones independently, she noted.

Because the neurostimulation occurs in response to aberrant electrical activity, fewer electrical impulses are delivered than would occur with continuous stimulation. This diminishes the risk of treatment-related adverse events, Dr. Morrell explained.

In an initial feasibility study of 65 patients, the responsive neurostimulation system demonstrated excellent safety, tolerability, and preliminary evidence of efficacy, Dr. Morrell said. “There were no serious device-related adverse events, and stimulation-related symptoms experienced by several subjects were addressed by adjusting the stimulation settings.”

A minimum 50% reduction in seizure frequency was achieved in 43% of the patients with complex partial seizures and 35% of those with total disabling seizures (Neurotherapeutics 2008;5:68-74).

In the double-blind pivotal trial, the 191 patients were randomized to active or sham therapy. All were 18-70 years of age (median 35 years), and all had partial onset epilepsy localized to one or two foci and had failed at least two antiepileptic medications.

The patients were taking an average of three antiepileptic medications to attempt seizure control; 34% had been treated previously with vagus nerve stimulation, 33% had prior surgical resection, and 16% had been treated with both.

“These patients tended to be very ill. Most of them had epilepsy for more than 20 years, and many were having at least three seizures per 28-day period—often many more than that,” Dr. Morrell said.

Of the 191 patients implanted with the device, 50% had mesial temporal seizure onset, 42% had neocortical seizure onset, and 8% had both, Dr. Morrell said at a press briefing during the meeting.

An initial, 12-week period prior to system implantation, during which baseline seizure activity was collected, was followed by a 12-week blinded period when participants were randomly assigned to have the responsive stimulation activated or left inactive, she said.

At each of the 31 trial sites, the patients and one neurologist were blinded to stimulation status, while a separate neurologist programmed the devices in order to maintain the study blinding. The responsive stimulation was optimized in the treatment over the next 4 weeks, followed by 84 days of data collection. At the end of the blinded efficacy period, stimulation was activated for all of the study participants for 2 years.

There were no serious, unanticipated device-related adverse events during the trial, nor was there a difference between the two groups with respect to the rate of adverse events, including depression, memory impairment, and anxiety, Dr. Morrell reported.

The findings suggest that responsive neurostimulation might be a promising treatment option for patients with seizures that are resistant to conventional antiepileptic therapy. The apparent increase in the number of patients experiencing at least a 50% reduction in seizure frequency relative to baseline during the open-label phase of the study suggests the system might become more effective over time, she noted.

The system has not yet received Food and Drug Administration approval, but NeuroPace plans to submit a premarket approval application to the FDA in early 2010, Dr. Morrell said.

Major Finding: Seizure frequency declined by a mean of 29% during active stimulation with the device over the first 12 weeks, compared with a 14% reduction during sham activation.

Data Source: Multicenter, randomized, sham-controlled clinical trial of 191 patients with medically intractable, partial onset seizures.

Disclosures: Dr. Morrell is the chief medical officer of NeuroPace, which developed the system and funded the trial.

BOSTON — Patients with treatment-resistant epilepsy can reduce seizure frequency with the use of an implantable device that detects preseizure electrical activity and aborts seizures, the results of a multicenter, randomized trial suggest.

In 191 patients with medically intractable, partial onset seizures who were implanted with the neurostimulator, seizures declined by a mean of 29% during active stimulation with the device, compared with a 14% reduction during sham activation, Dr. Martha J. Morrell reported at the annual meeting of the American Epilepsy Society.

In the later, open-label phase of the study in which all patients received active stimulation, nearly half of the 171 patients for whom 12 weeks of data were available had at least a 50% reduction in seizure frequency relative to baseline, said Dr. Morrell, clinical professor of neurology at Stanford (Calif.) University and chief medical officer of NeuroPace, developer of the Responsive Neurostimulator System (RNS).

The cranially implanted RNS device differs from conventional, “open loop” brain stimulation technologies that involve the scheduled delivery of electrical stimulation to specific brain regions independent of brain activity.

“The RNS delivers stimulation in response to a detected event,” Dr. Morrell said. The “individualized and dynamic” treatment responds to patterns of brain activity specific to a patient's seizure pattern. The electrodes are implanted in epileptic regions of the brain and connected to the battery-powered neurostimulator embedded in the skull.

“The programming is done wirelessly by the physician via a laptop computer,” Dr. Morrell said. “It's highly modifiable in that the physician can view the patient's electrocorticographic activity in real-time and change the [signal-detection] criteria at any time based on individual patient characteristics.”

Up to two leads, each containing four electrodes, can be connected to the neurostimulator, so the system can monitor and stimulate two distinct epileptogenic zones independently, she noted.

Because the neurostimulation occurs in response to aberrant electrical activity, fewer electrical impulses are delivered than would occur with continuous stimulation. This diminishes the risk of treatment-related adverse events, Dr. Morrell explained.

In an initial feasibility study of 65 patients, the responsive neurostimulation system demonstrated excellent safety, tolerability, and preliminary evidence of efficacy, Dr. Morrell said. “There were no serious device-related adverse events, and stimulation-related symptoms experienced by several subjects were addressed by adjusting the stimulation settings.”

A minimum 50% reduction in seizure frequency was achieved in 43% of the patients with complex partial seizures and 35% of those with total disabling seizures (Neurotherapeutics 2008;5:68-74).

In the double-blind pivotal trial, the 191 patients were randomized to active or sham therapy. All were 18-70 years of age (median 35 years), and all had partial onset epilepsy localized to one or two foci and had failed at least two antiepileptic medications.

The patients were taking an average of three antiepileptic medications to attempt seizure control; 34% had been treated previously with vagus nerve stimulation, 33% had prior surgical resection, and 16% had been treated with both.

“These patients tended to be very ill. Most of them had epilepsy for more than 20 years, and many were having at least three seizures per 28-day period—often many more than that,” Dr. Morrell said.

Of the 191 patients implanted with the device, 50% had mesial temporal seizure onset, 42% had neocortical seizure onset, and 8% had both, Dr. Morrell said at a press briefing during the meeting.

An initial, 12-week period prior to system implantation, during which baseline seizure activity was collected, was followed by a 12-week blinded period when participants were randomly assigned to have the responsive stimulation activated or left inactive, she said.

At each of the 31 trial sites, the patients and one neurologist were blinded to stimulation status, while a separate neurologist programmed the devices in order to maintain the study blinding. The responsive stimulation was optimized in the treatment over the next 4 weeks, followed by 84 days of data collection. At the end of the blinded efficacy period, stimulation was activated for all of the study participants for 2 years.

There were no serious, unanticipated device-related adverse events during the trial, nor was there a difference between the two groups with respect to the rate of adverse events, including depression, memory impairment, and anxiety, Dr. Morrell reported.

The findings suggest that responsive neurostimulation might be a promising treatment option for patients with seizures that are resistant to conventional antiepileptic therapy. The apparent increase in the number of patients experiencing at least a 50% reduction in seizure frequency relative to baseline during the open-label phase of the study suggests the system might become more effective over time, she noted.

The system has not yet received Food and Drug Administration approval, but NeuroPace plans to submit a premarket approval application to the FDA in early 2010, Dr. Morrell said.

Washington – Think globally, but act locally. The political mantra is perfectly suited to describe the necessary approach to not only improving the diagnosis and management of autoimmune diseases, but also to curing and eventually preventing them altogether, Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

“In addition to looking at each autoimmune disease as an important topic that merits medical attention and research emphasis, we have to look at the common problems of autoimmune diseases,” said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. Identifying the shared features will likely provide clues to the causes, and ultimately to the cures, he said.

Additionally, when considered collectively as a family of diseases rather than multiple individual disorders, the scope of the public health impact of autoimmune conditions cannot be ignored, said Dr. Rose, alluding to data presented in a briefing report released at the meeting. The report contains an estimate that autoimmune diseases are responsible for more than $100 billion annually in direct health care costs. “We now realize the magnitude of the problem. Conservatively, we’re talking about at least about 80 diseases – although the number of diseases in which autoimmunity plays a significant role could probably be almost double that – and at least 20 million people who are affected,” he said. Despite being such a major public health threat, “it is obvious that the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Rose said.

Some of the research, development, and management deficits are highlighted in the AARDA publication, titled “A Briefing Report on Autoimmune Disease and AARDA: Past, Present and Future.” The report contains an assessment of autoimmune diseases, including the most recent data on incidence, prevalence, and etiology. Current and pipeline therapies and trends in research funding are also discussed in the report. For example, most of the currently available therapies target fewer than 10% of the unique autoimmune or autoimmune-related diseases, and new drug development programs only target approximately 30%, according to the report, which will be made available through the AARDA website.

The report also identifies inconsistencies in incidence and prevalence data for autoimmune diseases individually and collectively. The analysis suggests that the actual annual direct and indirect costs of autoimmune diseases likely far exceed the $100 billion estimate. The costs associated with the seven major autoimmune diseases – Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma – are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose. The drug development process can take from 7-10 years and the current pipeline lacks drug candidates for more than 70% of the known autoimmune diseases. In light of those hard facts, the most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. The basic research endeavors – the identification of new targets for drugs that could go into development and the discovery of pathways for cells and networks that might be targets for future development, for example – are especially important, Dr. Daniel Rotrosen said at the summit. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that’s important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases.”

Although clinical trials consume significantly less of the NIH research funding overall, there are some dedicated clinical research networks at the National Institute of Allergy and Infectious Diseases (NIAID), including the Immune Tolerance Network, as well as nine Autoimmune Centers of Excellence across the country. Another research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis. Another effort involves predominantly preclinical autoimmune disease prevention centers focusing on cutting-edge bench and animal research that is intended to lead prevention strategies later on in clinical studies, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation (DAIT) at NIAID.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease and one-third for other conditions,” Dr. Rotrosen stated, noting that clinical trials in this arena are notoriously difficult. In particular, “the complexity and chronicity of autoimmune diseases present many challenges clinically,” he said. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

There are also numerous program and operational challenges associated with subject recruitment. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, said Dr. Rotrosen said. In autoimmune disease research, this helps investigators explore the mechanisms of disease progression and get a sense of the impact of therapies over time. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said. Additionally, the NIAID offers generous support for mechanistic studies and biomarker discovery, “which hopefully will lead to earlier, more accurate diagnoses, and will allow us to stratify subjects based on stage of disease, family history, genetic background, and so forth, so we can ultimately simplify trial designs and make them shorter and less costly.”

Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

Washington – Think globally, but act locally. The political mantra is perfectly suited to describe the necessary approach to not only improving the diagnosis and management of autoimmune diseases, but also to curing and eventually preventing them altogether, Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

“In addition to looking at each autoimmune disease as an important topic that merits medical attention and research emphasis, we have to look at the common problems of autoimmune diseases,” said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. Identifying the shared features will likely provide clues to the causes, and ultimately to the cures, he said.

Additionally, when considered collectively as a family of diseases rather than multiple individual disorders, the scope of the public health impact of autoimmune conditions cannot be ignored, said Dr. Rose, alluding to data presented in a briefing report released at the meeting. The report contains an estimate that autoimmune diseases are responsible for more than $100 billion annually in direct health care costs. “We now realize the magnitude of the problem. Conservatively, we’re talking about at least about 80 diseases – although the number of diseases in which autoimmunity plays a significant role could probably be almost double that – and at least 20 million people who are affected,” he said. Despite being such a major public health threat, “it is obvious that the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Rose said.

Some of the research, development, and management deficits are highlighted in the AARDA publication, titled “A Briefing Report on Autoimmune Disease and AARDA: Past, Present and Future.” The report contains an assessment of autoimmune diseases, including the most recent data on incidence, prevalence, and etiology. Current and pipeline therapies and trends in research funding are also discussed in the report. For example, most of the currently available therapies target fewer than 10% of the unique autoimmune or autoimmune-related diseases, and new drug development programs only target approximately 30%, according to the report, which will be made available through the AARDA website.

The report also identifies inconsistencies in incidence and prevalence data for autoimmune diseases individually and collectively. The analysis suggests that the actual annual direct and indirect costs of autoimmune diseases likely far exceed the $100 billion estimate. The costs associated with the seven major autoimmune diseases – Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma – are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose. The drug development process can take from 7-10 years and the current pipeline lacks drug candidates for more than 70% of the known autoimmune diseases. In light of those hard facts, the most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. The basic research endeavors – the identification of new targets for drugs that could go into development and the discovery of pathways for cells and networks that might be targets for future development, for example – are especially important, Dr. Daniel Rotrosen said at the summit. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that’s important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases.”

Although clinical trials consume significantly less of the NIH research funding overall, there are some dedicated clinical research networks at the National Institute of Allergy and Infectious Diseases (NIAID), including the Immune Tolerance Network, as well as nine Autoimmune Centers of Excellence across the country. Another research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis. Another effort involves predominantly preclinical autoimmune disease prevention centers focusing on cutting-edge bench and animal research that is intended to lead prevention strategies later on in clinical studies, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation (DAIT) at NIAID.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease and one-third for other conditions,” Dr. Rotrosen stated, noting that clinical trials in this arena are notoriously difficult. In particular, “the complexity and chronicity of autoimmune diseases present many challenges clinically,” he said. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

There are also numerous program and operational challenges associated with subject recruitment. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, said Dr. Rotrosen said. In autoimmune disease research, this helps investigators explore the mechanisms of disease progression and get a sense of the impact of therapies over time. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said. Additionally, the NIAID offers generous support for mechanistic studies and biomarker discovery, “which hopefully will lead to earlier, more accurate diagnoses, and will allow us to stratify subjects based on stage of disease, family history, genetic background, and so forth, so we can ultimately simplify trial designs and make them shorter and less costly.”

Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

Washington – Think globally, but act locally. The political mantra is perfectly suited to describe the necessary approach to not only improving the diagnosis and management of autoimmune diseases, but also to curing and eventually preventing them altogether, Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

“In addition to looking at each autoimmune disease as an important topic that merits medical attention and research emphasis, we have to look at the common problems of autoimmune diseases,” said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. Identifying the shared features will likely provide clues to the causes, and ultimately to the cures, he said.

Additionally, when considered collectively as a family of diseases rather than multiple individual disorders, the scope of the public health impact of autoimmune conditions cannot be ignored, said Dr. Rose, alluding to data presented in a briefing report released at the meeting. The report contains an estimate that autoimmune diseases are responsible for more than $100 billion annually in direct health care costs. “We now realize the magnitude of the problem. Conservatively, we’re talking about at least about 80 diseases – although the number of diseases in which autoimmunity plays a significant role could probably be almost double that – and at least 20 million people who are affected,” he said. Despite being such a major public health threat, “it is obvious that the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Rose said.

Some of the research, development, and management deficits are highlighted in the AARDA publication, titled “A Briefing Report on Autoimmune Disease and AARDA: Past, Present and Future.” The report contains an assessment of autoimmune diseases, including the most recent data on incidence, prevalence, and etiology. Current and pipeline therapies and trends in research funding are also discussed in the report. For example, most of the currently available therapies target fewer than 10% of the unique autoimmune or autoimmune-related diseases, and new drug development programs only target approximately 30%, according to the report, which will be made available through the AARDA website.

The report also identifies inconsistencies in incidence and prevalence data for autoimmune diseases individually and collectively. The analysis suggests that the actual annual direct and indirect costs of autoimmune diseases likely far exceed the $100 billion estimate. The costs associated with the seven major autoimmune diseases – Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma – are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose. The drug development process can take from 7-10 years and the current pipeline lacks drug candidates for more than 70% of the known autoimmune diseases. In light of those hard facts, the most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. The basic research endeavors – the identification of new targets for drugs that could go into development and the discovery of pathways for cells and networks that might be targets for future development, for example – are especially important, Dr. Daniel Rotrosen said at the summit. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that’s important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases.”

Although clinical trials consume significantly less of the NIH research funding overall, there are some dedicated clinical research networks at the National Institute of Allergy and Infectious Diseases (NIAID), including the Immune Tolerance Network, as well as nine Autoimmune Centers of Excellence across the country. Another research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis. Another effort involves predominantly preclinical autoimmune disease prevention centers focusing on cutting-edge bench and animal research that is intended to lead prevention strategies later on in clinical studies, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation (DAIT) at NIAID.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease and one-third for other conditions,” Dr. Rotrosen stated, noting that clinical trials in this arena are notoriously difficult. In particular, “the complexity and chronicity of autoimmune diseases present many challenges clinically,” he said. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

There are also numerous program and operational challenges associated with subject recruitment. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, said Dr. Rotrosen said. In autoimmune disease research, this helps investigators explore the mechanisms of disease progression and get a sense of the impact of therapies over time. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said. Additionally, the NIAID offers generous support for mechanistic studies and biomarker discovery, “which hopefully will lead to earlier, more accurate diagnoses, and will allow us to stratify subjects based on stage of disease, family history, genetic background, and so forth, so we can ultimately simplify trial designs and make them shorter and less costly.”

Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

Major Finding: Sixty percent of patient-physician pairs studied agreed on the patient's top three health priorities; 29% of the the pairs had no matches in the top three priorities.

Data Source: Prospective cohort study of 92 primary care providers and 1,169 of their diabetic patients with comorbid hypertension.

Disclosures: The study was supported by the Robert Wood Johnson Clinical Scholars Program. The authors reported having no financial disclosures.

Diabetes patients with multiple health concerns are not always in sync with their physicians regarding the relative importance of specific comorbidities, and this incongruity could have clinical management implications, according to a report by University of Michigan researchers.

In a prospective cohort study designed to assess concordance of patient and physician priorities, Dr. Donna M. Zulman and her colleagues at the university in Ann Arbor surveyed 92 primary care providers and 1,169 of their diabetes patients. Patients ranked their most important health concerns and providers ranked the most important conditions likely to affect the patients' health outcomes. For 60% of the patient-provider pairs, concordance was high: The provider ranked the same top three health concerns as did the patient, or ranked two of the same health concerns, and these two matched the patient's most important concerns. For 72% of the patient-provider pairs, the patient's most important concern was on the provider's top-three list, but 16% of the pairs had three matching health concerns, 55% had two, 25% had one, and 4% had none, they wrote (J. Gen. Intern. Med. 2010 Feb. 2 [Epub doi: 10.1007/s11606-009-1232-1]).

The discordance in perception of hypertension as the most important comorbidity was especially notable. “Although providers ranked hypertension as the most important health condition for 384 (38%) patients, only 184 (18%) patients listed hypertension as their most important health concern,” they wrote. “Patients were more likely than providers to list 'losing weight or being more active' in their top three concerns (35% vs. 21%, respectively).” This finding is consistent with previous data suggesting that many diabetic patients are not aware of the importance of blood pressure control despite the available evidence and clinical guidelines, the authors said.

Another striking disconnect was observed in patients who listed pain or depression as their top health concern relative to the number of their providers who ranked these conditions as likely to affect health outcomes. For example, 9% of patients who listed pain as their top health concern had a provider who ranked it among the top three, and 32% who listed depression as their most important comorbidity had physicians who agreed. “This discordance is concerning, not only because it raises the possibility that providers are unaware of the extent to which these conditions affect their patients, but also because pain and depression can be barriers to effective diabetes self-management, and (in the case of depression) may worsen glycemic control and increase the risk of mortality,” the authors noted. “By deemphasizing symptomatic conditions, providers are actually neglecting some of the most important medical concerns that are likely to affect health outcomes in these patients.”

Study limitations included the inability of the concordance score to measure the concept of which conditions the providers thought the patients would prioritize, and the fact that the patients and providers were aware that the study was looking at diabetic patients with an elevated blood pressure level at triage, thus making it more likely that hypertension and diabetes would be listed among the top three health concerns and potentially hindering the evaluation of concordance patterns among other health conditions, the authors wrote.

The findings “reinforce the need for heightened provider recognition of patients' symptomatic conditions as well as their non-health competing demands.”

Major Finding: Sixty percent of patient-physician pairs studied agreed on the patient's top three health priorities; 29% of the the pairs had no matches in the top three priorities.

Data Source: Prospective cohort study of 92 primary care providers and 1,169 of their diabetic patients with comorbid hypertension.

Disclosures: The study was supported by the Robert Wood Johnson Clinical Scholars Program. The authors reported having no financial disclosures.

Diabetes patients with multiple health concerns are not always in sync with their physicians regarding the relative importance of specific comorbidities, and this incongruity could have clinical management implications, according to a report by University of Michigan researchers.

In a prospective cohort study designed to assess concordance of patient and physician priorities, Dr. Donna M. Zulman and her colleagues at the university in Ann Arbor surveyed 92 primary care providers and 1,169 of their diabetes patients. Patients ranked their most important health concerns and providers ranked the most important conditions likely to affect the patients' health outcomes. For 60% of the patient-provider pairs, concordance was high: The provider ranked the same top three health concerns as did the patient, or ranked two of the same health concerns, and these two matched the patient's most important concerns. For 72% of the patient-provider pairs, the patient's most important concern was on the provider's top-three list, but 16% of the pairs had three matching health concerns, 55% had two, 25% had one, and 4% had none, they wrote (J. Gen. Intern. Med. 2010 Feb. 2 [Epub doi: 10.1007/s11606-009-1232-1]).

The discordance in perception of hypertension as the most important comorbidity was especially notable. “Although providers ranked hypertension as the most important health condition for 384 (38%) patients, only 184 (18%) patients listed hypertension as their most important health concern,” they wrote. “Patients were more likely than providers to list 'losing weight or being more active' in their top three concerns (35% vs. 21%, respectively).” This finding is consistent with previous data suggesting that many diabetic patients are not aware of the importance of blood pressure control despite the available evidence and clinical guidelines, the authors said.

Another striking disconnect was observed in patients who listed pain or depression as their top health concern relative to the number of their providers who ranked these conditions as likely to affect health outcomes. For example, 9% of patients who listed pain as their top health concern had a provider who ranked it among the top three, and 32% who listed depression as their most important comorbidity had physicians who agreed. “This discordance is concerning, not only because it raises the possibility that providers are unaware of the extent to which these conditions affect their patients, but also because pain and depression can be barriers to effective diabetes self-management, and (in the case of depression) may worsen glycemic control and increase the risk of mortality,” the authors noted. “By deemphasizing symptomatic conditions, providers are actually neglecting some of the most important medical concerns that are likely to affect health outcomes in these patients.”

Study limitations included the inability of the concordance score to measure the concept of which conditions the providers thought the patients would prioritize, and the fact that the patients and providers were aware that the study was looking at diabetic patients with an elevated blood pressure level at triage, thus making it more likely that hypertension and diabetes would be listed among the top three health concerns and potentially hindering the evaluation of concordance patterns among other health conditions, the authors wrote.

The findings “reinforce the need for heightened provider recognition of patients' symptomatic conditions as well as their non-health competing demands.”

Major Finding: Sixty percent of patient-physician pairs studied agreed on the patient's top three health priorities; 29% of the the pairs had no matches in the top three priorities.

Data Source: Prospective cohort study of 92 primary care providers and 1,169 of their diabetic patients with comorbid hypertension.

Disclosures: The study was supported by the Robert Wood Johnson Clinical Scholars Program. The authors reported having no financial disclosures.

Diabetes patients with multiple health concerns are not always in sync with their physicians regarding the relative importance of specific comorbidities, and this incongruity could have clinical management implications, according to a report by University of Michigan researchers.

In a prospective cohort study designed to assess concordance of patient and physician priorities, Dr. Donna M. Zulman and her colleagues at the university in Ann Arbor surveyed 92 primary care providers and 1,169 of their diabetes patients. Patients ranked their most important health concerns and providers ranked the most important conditions likely to affect the patients' health outcomes. For 60% of the patient-provider pairs, concordance was high: The provider ranked the same top three health concerns as did the patient, or ranked two of the same health concerns, and these two matched the patient's most important concerns. For 72% of the patient-provider pairs, the patient's most important concern was on the provider's top-three list, but 16% of the pairs had three matching health concerns, 55% had two, 25% had one, and 4% had none, they wrote (J. Gen. Intern. Med. 2010 Feb. 2 [Epub doi: 10.1007/s11606-009-1232-1]).

The discordance in perception of hypertension as the most important comorbidity was especially notable. “Although providers ranked hypertension as the most important health condition for 384 (38%) patients, only 184 (18%) patients listed hypertension as their most important health concern,” they wrote. “Patients were more likely than providers to list 'losing weight or being more active' in their top three concerns (35% vs. 21%, respectively).” This finding is consistent with previous data suggesting that many diabetic patients are not aware of the importance of blood pressure control despite the available evidence and clinical guidelines, the authors said.

Another striking disconnect was observed in patients who listed pain or depression as their top health concern relative to the number of their providers who ranked these conditions as likely to affect health outcomes. For example, 9% of patients who listed pain as their top health concern had a provider who ranked it among the top three, and 32% who listed depression as their most important comorbidity had physicians who agreed. “This discordance is concerning, not only because it raises the possibility that providers are unaware of the extent to which these conditions affect their patients, but also because pain and depression can be barriers to effective diabetes self-management, and (in the case of depression) may worsen glycemic control and increase the risk of mortality,” the authors noted. “By deemphasizing symptomatic conditions, providers are actually neglecting some of the most important medical concerns that are likely to affect health outcomes in these patients.”

Study limitations included the inability of the concordance score to measure the concept of which conditions the providers thought the patients would prioritize, and the fact that the patients and providers were aware that the study was looking at diabetic patients with an elevated blood pressure level at triage, thus making it more likely that hypertension and diabetes would be listed among the top three health concerns and potentially hindering the evaluation of concordance patterns among other health conditions, the authors wrote.

The findings “reinforce the need for heightened provider recognition of patients' symptomatic conditions as well as their non-health competing demands.”

Major Finding: Based on a composite index for measuring the impact of RA, pain ranked highest at 21% followed by functional disability at 16% and fatigue at 15%.

Data Source: Rankings from 100 patients, 10 patients in 10 countries, on the Rheumatoid Arthritis Impact of Disease scoring system.

Disclosures: The investigators reported no relevant disclosures.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains on a 1-17 scale, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact.

Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The mean age and disease duration of the patients participating in the weighting process was 56 years and 15 years, respectively. Additionally, the group's mean Health Assessment Questionnaire (HAQ) score was 1.23, the authors wrote. The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated.

“The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more complete validated instrument or questionnaire.

Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote.

“In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec.

Major Finding: Based on a composite index for measuring the impact of RA, pain ranked highest at 21% followed by functional disability at 16% and fatigue at 15%.

Data Source: Rankings from 100 patients, 10 patients in 10 countries, on the Rheumatoid Arthritis Impact of Disease scoring system.

Disclosures: The investigators reported no relevant disclosures.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains on a 1-17 scale, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact.

Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The mean age and disease duration of the patients participating in the weighting process was 56 years and 15 years, respectively. Additionally, the group's mean Health Assessment Questionnaire (HAQ) score was 1.23, the authors wrote. The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated.

“The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more complete validated instrument or questionnaire.

Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote.

“In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec.

Major Finding: Based on a composite index for measuring the impact of RA, pain ranked highest at 21% followed by functional disability at 16% and fatigue at 15%.

Data Source: Rankings from 100 patients, 10 patients in 10 countries, on the Rheumatoid Arthritis Impact of Disease scoring system.

Disclosures: The investigators reported no relevant disclosures.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains on a 1-17 scale, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact.

Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The mean age and disease duration of the patients participating in the weighting process was 56 years and 15 years, respectively. Additionally, the group's mean Health Assessment Questionnaire (HAQ) score was 1.23, the authors wrote. The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated.

“The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more complete validated instrument or questionnaire.

Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote.

“In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec.

Major Finding: In the 30 months prior to the publication of the clinical guideline, 11% of the AOM diagnoses were managed without an antibiotic, compared with 16% after the guideline publication, a nonsignificant difference.

Data Source: National Ambulatory Medical Care Survey, 2002-2006.

Disclosures: None reported.

The percentage of pediatric acute otitis media visits during which an antibiotic was not prescribed did not increase significantly in the 30 months after the dissemination in 2004 of the well-publicized clinical practice guideline that allowed for patient observation without initial antibiotic therapy, according to a report.

Dr. Andrew Coco of the Lancaster (Pa.) General Research Institute and his colleagues analyzed data on 1,114 acute otitis media (AOM) patients aged 6 months to 12 years that were collected between 2002 and 2006 as part of the National Ambulatory Medical Care Survey, comparing the clinical management strategies during the 30-month periods before and after the publication of the 2004 American Academy of Pediatrics and American Academy of Family Physicians clinical practice guideline.

The primary study end point was the rate of AOM encounters with no reported antibiotic prescribing. Secondary end points were predictors of AOM encounters at which no antibiotic prescribing was reported and the rates of antibiotic prescribing and analgesic prescribing. Eighty-two percent of visits were with pediatricians, 14% were with family physicians, and 4% were with other physicians (Pediatrics 2010;125:214-20).

During the period of study overall, antibiotics were not prescribed in 13% of the visits, according to the analysis. In the 30 months prior to the publication of the clinical guideline, 11% of the AOM diagnoses were managed without an antibiotic, compared with 16% after the guideline publication, which does not represent a statistically significant difference, the authors reported.

“Although the results of our analysis demonstrate a slightly increased trend in the management of AOM without antibiotics over the study period, the absence of an inflection point around the time of the guideline publication argues against the guideline being a large factor in what more likely represents a general secular trend,” Dr. Coco and his associates wrote.

“It seems that, despite the guideline's endorsement, physicians have been reluctant to frequently use the observation option, perhaps because of perceptions of parental reluctance to accept this approach and barriers to follow-up.”

Independent predictors of a patient visit at which antibiotic prescribing was not reported included the absence of ear pain, the absence of fever, and receipt of an analgesic prescription, according to multivariate logistic regression modeling.

“It is encouraging that children who did not receive antibiotics were also less likely to present with symptoms of severe infection, such as fever or ear pain,” the authors wrote. “Thus, consistent with the guideline, it seems that the initial observation option was more likely to be chosen in children with mild infections.”

An unexpected finding, according to the authors, was the fact that amoxicillin/clavulanate prescribing, which the guideline recommends for the treatment of children with severe infection and those with treatment failure, decreased from 23% to 16%. This finding is, however, consistent with physicians' historical lack of enthusiasm for prescribing the combination treatment for severe infections, Dr. Coco and his associates said.

Physicians in the study “were choosing cefdinir as a second-line agent instead, perhaps because of a more convenient dosing schedule, a lower incidence of diarrhea, or more aggressive marketing,” the investigators wrote. Its use doubled from 7% to 14% of all antibiotics prescribed after publication of the guideline.

The proportion of visits at which amoxicillin was prescribed increased from 40% to 49%, which is consistent with the guideline recommendation, the authors noted.

The rate of analgesic prescribing also increased from 14% to 24%—an indication that pediatric providers “have accepted this strong recommendation to treat the pain that is often associated with AOM, which is a reversal of previous findings showing that treating otalgia is not prioritized by clinicians,” Dr. Coco and his associates wrote.

“It would seem that physicians were more willing to adopt a recommendation from the guideline to add a treatment [analgesic agents] rather than to withhold one [antibiotics].”

In an accompanying editorial, Dr. Robert Siegel of Cincinnati Children's Hospital Medical Center suggested that family education about antibiotic use and AOM pain management might yield the most success with respect to meeting guideline recommendations.

“Today's patients and families are more medically sophisticated than the last generation, because they have greater access to information,” he wrote. “Health care providers should embrace and encourage this empowerment and involve patients in shared decision making regarding whether to use antibiotics for otitis media” (Pediatrics 2010;125:384-6).

Family education about antibiotic use might make physician compliance with the guideline more likely.

Source DR. SIEGEL

My Take

No Surprises in This Study

The finding that the 2004 AAP/AAFP guideline for AOM treatment has not substantially increased the proportion of the pediatric AOM cases being managed without antibiotics is not especially surprising.

Many physicians are uncomfortable with the watchful waiting recommendation because there is reasonable evidence that certain children benefit significantly from antibiotics. For example, the findings of a recent meta-analysis suggest that antibiotics are effective for the treatment of AOM in children younger than 2 years old who have bilateral disease and in children with both otorrhea and AOM (Lancet 2006;368:1429-35).

Additionally, the guideline calls for the use of antibiotics for the treatment of severe disease, which is a subjective characterization.

The gap between the guideline recommendations and clinical practice will likely widen further in the near future, with the upcoming publication of new studies linking watchful waiting with a greater proportion of children in whom the signs and symptoms of AOM last beyond 3 or 4 days.

Despite the guideline controversy, the reduction of antibiotic prescribing continues to be an important goal. To achieve it, we should focus on developing a vaccine that prevents viral and bacterial respiratory tract infections, practicing restraint in treating nonfocal upper respiratory tract infections with antibiotics, and establishing more accurate diagnostic criteria for AOM and sinusitis.

Another important goal should be the selection of appropriate antibiotics for the likely pathogens. Currently, the spectrum of antibiotics that are prescribed portray a lack of understanding of the effectiveness of various antibiotics against various pathogens.

For example, data on the increase in the use of azithromycin are problematic as it is a drug with a long half-life and is believed to promote the emergence of resistance to a greater extent than some other antibiotics.

Even so, studies have shown that pediatricians choose azithromycin twice as often in children with recurrent AOM, which is backward, as it would be less likely to be effective in a recurrent episode than in a first.

I think this confirms that selection of antibiotics is based more on convenience, taste, and possibly marketing than on an understanding of the activity and limitations of the antibiotic.

Major Finding: In the 30 months prior to the publication of the clinical guideline, 11% of the AOM diagnoses were managed without an antibiotic, compared with 16% after the guideline publication, a nonsignificant difference.

Data Source: National Ambulatory Medical Care Survey, 2002-2006.

Disclosures: None reported.

The percentage of pediatric acute otitis media visits during which an antibiotic was not prescribed did not increase significantly in the 30 months after the dissemination in 2004 of the well-publicized clinical practice guideline that allowed for patient observation without initial antibiotic therapy, according to a report.

Dr. Andrew Coco of the Lancaster (Pa.) General Research Institute and his colleagues analyzed data on 1,114 acute otitis media (AOM) patients aged 6 months to 12 years that were collected between 2002 and 2006 as part of the National Ambulatory Medical Care Survey, comparing the clinical management strategies during the 30-month periods before and after the publication of the 2004 American Academy of Pediatrics and American Academy of Family Physicians clinical practice guideline.

The primary study end point was the rate of AOM encounters with no reported antibiotic prescribing. Secondary end points were predictors of AOM encounters at which no antibiotic prescribing was reported and the rates of antibiotic prescribing and analgesic prescribing. Eighty-two percent of visits were with pediatricians, 14% were with family physicians, and 4% were with other physicians (Pediatrics 2010;125:214-20).

During the period of study overall, antibiotics were not prescribed in 13% of the visits, according to the analysis. In the 30 months prior to the publication of the clinical guideline, 11% of the AOM diagnoses were managed without an antibiotic, compared with 16% after the guideline publication, which does not represent a statistically significant difference, the authors reported.

“Although the results of our analysis demonstrate a slightly increased trend in the management of AOM without antibiotics over the study period, the absence of an inflection point around the time of the guideline publication argues against the guideline being a large factor in what more likely represents a general secular trend,” Dr. Coco and his associates wrote.

“It seems that, despite the guideline's endorsement, physicians have been reluctant to frequently use the observation option, perhaps because of perceptions of parental reluctance to accept this approach and barriers to follow-up.”

Independent predictors of a patient visit at which antibiotic prescribing was not reported included the absence of ear pain, the absence of fever, and receipt of an analgesic prescription, according to multivariate logistic regression modeling.

“It is encouraging that children who did not receive antibiotics were also less likely to present with symptoms of severe infection, such as fever or ear pain,” the authors wrote. “Thus, consistent with the guideline, it seems that the initial observation option was more likely to be chosen in children with mild infections.”

An unexpected finding, according to the authors, was the fact that amoxicillin/clavulanate prescribing, which the guideline recommends for the treatment of children with severe infection and those with treatment failure, decreased from 23% to 16%. This finding is, however, consistent with physicians' historical lack of enthusiasm for prescribing the combination treatment for severe infections, Dr. Coco and his associates said.

Physicians in the study “were choosing cefdinir as a second-line agent instead, perhaps because of a more convenient dosing schedule, a lower incidence of diarrhea, or more aggressive marketing,” the investigators wrote. Its use doubled from 7% to 14% of all antibiotics prescribed after publication of the guideline.

The proportion of visits at which amoxicillin was prescribed increased from 40% to 49%, which is consistent with the guideline recommendation, the authors noted.

The rate of analgesic prescribing also increased from 14% to 24%—an indication that pediatric providers “have accepted this strong recommendation to treat the pain that is often associated with AOM, which is a reversal of previous findings showing that treating otalgia is not prioritized by clinicians,” Dr. Coco and his associates wrote.

“It would seem that physicians were more willing to adopt a recommendation from the guideline to add a treatment [analgesic agents] rather than to withhold one [antibiotics].”

In an accompanying editorial, Dr. Robert Siegel of Cincinnati Children's Hospital Medical Center suggested that family education about antibiotic use and AOM pain management might yield the most success with respect to meeting guideline recommendations.

“Today's patients and families are more medically sophisticated than the last generation, because they have greater access to information,” he wrote. “Health care providers should embrace and encourage this empowerment and involve patients in shared decision making regarding whether to use antibiotics for otitis media” (Pediatrics 2010;125:384-6).

Family education about antibiotic use might make physician compliance with the guideline more likely.

Source DR. SIEGEL

My Take

No Surprises in This Study

The finding that the 2004 AAP/AAFP guideline for AOM treatment has not substantially increased the proportion of the pediatric AOM cases being managed without antibiotics is not especially surprising.

Many physicians are uncomfortable with the watchful waiting recommendation because there is reasonable evidence that certain children benefit significantly from antibiotics. For example, the findings of a recent meta-analysis suggest that antibiotics are effective for the treatment of AOM in children younger than 2 years old who have bilateral disease and in children with both otorrhea and AOM (Lancet 2006;368:1429-35).

Additionally, the guideline calls for the use of antibiotics for the treatment of severe disease, which is a subjective characterization.

The gap between the guideline recommendations and clinical practice will likely widen further in the near future, with the upcoming publication of new studies linking watchful waiting with a greater proportion of children in whom the signs and symptoms of AOM last beyond 3 or 4 days.

Despite the guideline controversy, the reduction of antibiotic prescribing continues to be an important goal. To achieve it, we should focus on developing a vaccine that prevents viral and bacterial respiratory tract infections, practicing restraint in treating nonfocal upper respiratory tract infections with antibiotics, and establishing more accurate diagnostic criteria for AOM and sinusitis.

Another important goal should be the selection of appropriate antibiotics for the likely pathogens. Currently, the spectrum of antibiotics that are prescribed portray a lack of understanding of the effectiveness of various antibiotics against various pathogens.

For example, data on the increase in the use of azithromycin are problematic as it is a drug with a long half-life and is believed to promote the emergence of resistance to a greater extent than some other antibiotics.

Even so, studies have shown that pediatricians choose azithromycin twice as often in children with recurrent AOM, which is backward, as it would be less likely to be effective in a recurrent episode than in a first.

I think this confirms that selection of antibiotics is based more on convenience, taste, and possibly marketing than on an understanding of the activity and limitations of the antibiotic.

Major Finding: In the 30 months prior to the publication of the clinical guideline, 11% of the AOM diagnoses were managed without an antibiotic, compared with 16% after the guideline publication, a nonsignificant difference.

Data Source: National Ambulatory Medical Care Survey, 2002-2006.

Disclosures: None reported.

The percentage of pediatric acute otitis media visits during which an antibiotic was not prescribed did not increase significantly in the 30 months after the dissemination in 2004 of the well-publicized clinical practice guideline that allowed for patient observation without initial antibiotic therapy, according to a report.

Dr. Andrew Coco of the Lancaster (Pa.) General Research Institute and his colleagues analyzed data on 1,114 acute otitis media (AOM) patients aged 6 months to 12 years that were collected between 2002 and 2006 as part of the National Ambulatory Medical Care Survey, comparing the clinical management strategies during the 30-month periods before and after the publication of the 2004 American Academy of Pediatrics and American Academy of Family Physicians clinical practice guideline.

The primary study end point was the rate of AOM encounters with no reported antibiotic prescribing. Secondary end points were predictors of AOM encounters at which no antibiotic prescribing was reported and the rates of antibiotic prescribing and analgesic prescribing. Eighty-two percent of visits were with pediatricians, 14% were with family physicians, and 4% were with other physicians (Pediatrics 2010;125:214-20).

During the period of study overall, antibiotics were not prescribed in 13% of the visits, according to the analysis. In the 30 months prior to the publication of the clinical guideline, 11% of the AOM diagnoses were managed without an antibiotic, compared with 16% after the guideline publication, which does not represent a statistically significant difference, the authors reported.

“Although the results of our analysis demonstrate a slightly increased trend in the management of AOM without antibiotics over the study period, the absence of an inflection point around the time of the guideline publication argues against the guideline being a large factor in what more likely represents a general secular trend,” Dr. Coco and his associates wrote.

“It seems that, despite the guideline's endorsement, physicians have been reluctant to frequently use the observation option, perhaps because of perceptions of parental reluctance to accept this approach and barriers to follow-up.”

Independent predictors of a patient visit at which antibiotic prescribing was not reported included the absence of ear pain, the absence of fever, and receipt of an analgesic prescription, according to multivariate logistic regression modeling.

“It is encouraging that children who did not receive antibiotics were also less likely to present with symptoms of severe infection, such as fever or ear pain,” the authors wrote. “Thus, consistent with the guideline, it seems that the initial observation option was more likely to be chosen in children with mild infections.”

An unexpected finding, according to the authors, was the fact that amoxicillin/clavulanate prescribing, which the guideline recommends for the treatment of children with severe infection and those with treatment failure, decreased from 23% to 16%. This finding is, however, consistent with physicians' historical lack of enthusiasm for prescribing the combination treatment for severe infections, Dr. Coco and his associates said.

Physicians in the study “were choosing cefdinir as a second-line agent instead, perhaps because of a more convenient dosing schedule, a lower incidence of diarrhea, or more aggressive marketing,” the investigators wrote. Its use doubled from 7% to 14% of all antibiotics prescribed after publication of the guideline.

The proportion of visits at which amoxicillin was prescribed increased from 40% to 49%, which is consistent with the guideline recommendation, the authors noted.

The rate of analgesic prescribing also increased from 14% to 24%—an indication that pediatric providers “have accepted this strong recommendation to treat the pain that is often associated with AOM, which is a reversal of previous findings showing that treating otalgia is not prioritized by clinicians,” Dr. Coco and his associates wrote.

“It would seem that physicians were more willing to adopt a recommendation from the guideline to add a treatment [analgesic agents] rather than to withhold one [antibiotics].”

In an accompanying editorial, Dr. Robert Siegel of Cincinnati Children's Hospital Medical Center suggested that family education about antibiotic use and AOM pain management might yield the most success with respect to meeting guideline recommendations.

“Today's patients and families are more medically sophisticated than the last generation, because they have greater access to information,” he wrote. “Health care providers should embrace and encourage this empowerment and involve patients in shared decision making regarding whether to use antibiotics for otitis media” (Pediatrics 2010;125:384-6).

Family education about antibiotic use might make physician compliance with the guideline more likely.

Source DR. SIEGEL

My Take

No Surprises in This Study

The finding that the 2004 AAP/AAFP guideline for AOM treatment has not substantially increased the proportion of the pediatric AOM cases being managed without antibiotics is not especially surprising.

Many physicians are uncomfortable with the watchful waiting recommendation because there is reasonable evidence that certain children benefit significantly from antibiotics. For example, the findings of a recent meta-analysis suggest that antibiotics are effective for the treatment of AOM in children younger than 2 years old who have bilateral disease and in children with both otorrhea and AOM (Lancet 2006;368:1429-35).

Additionally, the guideline calls for the use of antibiotics for the treatment of severe disease, which is a subjective characterization.

The gap between the guideline recommendations and clinical practice will likely widen further in the near future, with the upcoming publication of new studies linking watchful waiting with a greater proportion of children in whom the signs and symptoms of AOM last beyond 3 or 4 days.

Despite the guideline controversy, the reduction of antibiotic prescribing continues to be an important goal. To achieve it, we should focus on developing a vaccine that prevents viral and bacterial respiratory tract infections, practicing restraint in treating nonfocal upper respiratory tract infections with antibiotics, and establishing more accurate diagnostic criteria for AOM and sinusitis.

Another important goal should be the selection of appropriate antibiotics for the likely pathogens. Currently, the spectrum of antibiotics that are prescribed portray a lack of understanding of the effectiveness of various antibiotics against various pathogens.

For example, data on the increase in the use of azithromycin are problematic as it is a drug with a long half-life and is believed to promote the emergence of resistance to a greater extent than some other antibiotics.

Even so, studies have shown that pediatricians choose azithromycin twice as often in children with recurrent AOM, which is backward, as it would be less likely to be effective in a recurrent episode than in a first.

I think this confirms that selection of antibiotics is based more on convenience, taste, and possibly marketing than on an understanding of the activity and limitations of the antibiotic.

A mumps outbreak that began in New York in June and led to 1,521 reported cases of the disease as of Jan. 29, 2010, has prompted the Centers for Disease Control and Prevention to remind public health officials to be diligent in their surveillance and reporting and to be mindful that maintaining high measles, mumps, and rubella vaccination coverage remains the most effective way to prevent outbreaks and limit their size when they do occur.

In the Feb. 12 Morbidity and Mortality Weekly Report, the CDC describes the mumps outbreak, which began in a New York summer camp for tradition-observant Jewish boys and has spread substantially among members of tradition-observant Jewish communities in New York City, New Jersey, and two counties in upstate New York. The majority of the affected patients have been boys older than 6 years (median age, 15 years, among those whose age is known). To date, there have been 65 reports of mumps-related complications, 19 mumps-related hospitalizations, and no deaths, according to the report (MMWR 2010;59:125-9).

An assessment of MMR vaccination status, which was known in 1,115 of the cases, showed that 976 patients had received at least one dose before the outbreak and 839 had received two doses. This finding emphasizes the fact that mumps outbreaks can occur in highly vaccinated populations, which is likely attributable, in part, to the fact that the effectiveness of the mumps component of the MMR vaccine is lower than that of the measles and rubella components, according to an editorial note in the report. For this reason, public health officials in Orange County, N.Y., where transmission continued among students in three religious schools, despite high two-dose coverage, began offering a third MMR dose to students in the schools.

To date, “no data exist on the effectiveness of a third dose in either reducing the risk for mumps or altering the course of an outbreak,” nor has the CDC's Advisory Committee on Immunization Practices recommended a third dose, the authors stated. However, they noted, “a previous study indicated that a third dose of MMR vaccine for seronegative college students resulted in rapid seroconversion with a low rate of IgM response, which is indicative of an anamnestic immune response” (J. Infect. Dis. 2008;197:1662-8).

The authors hypothesized that the settings in which the outbreaks occurred—predominantly all-boys' schools where students spend long periods in large study halls and are often face to face with a study partner—and the relatively large household sizes of the affected community might be facilitating transmission within the community and limiting transmission outside it. They stress, however, that “the high vaccination coverage in the affected community likely is limiting the size of the outbreak.”

Additionally, high vaccination coverage outside the community might explain why the few cases that have occurred outside the community have not led to new outbreaks, the authors wrote.

While maintaining high MMR vaccination coverage doesn't prevent all mumps outbreaks, it remains the most effective preventive measure available, thus timely vaccination with two doses should be encouraged, according to the report.

The authors also advocated a high degree of awareness among health care providers that mumps can occur in areas of high vaccination coverage. Providers are urged to promptly report cases of mumps and isolate individuals with suspected or confirmed disease for 5 days after onset.

A mumps outbreak that began in New York in June and led to 1,521 reported cases of the disease as of Jan. 29, 2010, has prompted the Centers for Disease Control and Prevention to remind public health officials to be diligent in their surveillance and reporting and to be mindful that maintaining high measles, mumps, and rubella vaccination coverage remains the most effective way to prevent outbreaks and limit their size when they do occur.

In the Feb. 12 Morbidity and Mortality Weekly Report, the CDC describes the mumps outbreak, which began in a New York summer camp for tradition-observant Jewish boys and has spread substantially among members of tradition-observant Jewish communities in New York City, New Jersey, and two counties in upstate New York. The majority of the affected patients have been boys older than 6 years (median age, 15 years, among those whose age is known). To date, there have been 65 reports of mumps-related complications, 19 mumps-related hospitalizations, and no deaths, according to the report (MMWR 2010;59:125-9).

An assessment of MMR vaccination status, which was known in 1,115 of the cases, showed that 976 patients had received at least one dose before the outbreak and 839 had received two doses. This finding emphasizes the fact that mumps outbreaks can occur in highly vaccinated populations, which is likely attributable, in part, to the fact that the effectiveness of the mumps component of the MMR vaccine is lower than that of the measles and rubella components, according to an editorial note in the report. For this reason, public health officials in Orange County, N.Y., where transmission continued among students in three religious schools, despite high two-dose coverage, began offering a third MMR dose to students in the schools.

To date, “no data exist on the effectiveness of a third dose in either reducing the risk for mumps or altering the course of an outbreak,” nor has the CDC's Advisory Committee on Immunization Practices recommended a third dose, the authors stated. However, they noted, “a previous study indicated that a third dose of MMR vaccine for seronegative college students resulted in rapid seroconversion with a low rate of IgM response, which is indicative of an anamnestic immune response” (J. Infect. Dis. 2008;197:1662-8).

The authors hypothesized that the settings in which the outbreaks occurred—predominantly all-boys' schools where students spend long periods in large study halls and are often face to face with a study partner—and the relatively large household sizes of the affected community might be facilitating transmission within the community and limiting transmission outside it. They stress, however, that “the high vaccination coverage in the affected community likely is limiting the size of the outbreak.”

Additionally, high vaccination coverage outside the community might explain why the few cases that have occurred outside the community have not led to new outbreaks, the authors wrote.

While maintaining high MMR vaccination coverage doesn't prevent all mumps outbreaks, it remains the most effective preventive measure available, thus timely vaccination with two doses should be encouraged, according to the report.

The authors also advocated a high degree of awareness among health care providers that mumps can occur in areas of high vaccination coverage. Providers are urged to promptly report cases of mumps and isolate individuals with suspected or confirmed disease for 5 days after onset.

A mumps outbreak that began in New York in June and led to 1,521 reported cases of the disease as of Jan. 29, 2010, has prompted the Centers for Disease Control and Prevention to remind public health officials to be diligent in their surveillance and reporting and to be mindful that maintaining high measles, mumps, and rubella vaccination coverage remains the most effective way to prevent outbreaks and limit their size when they do occur.

In the Feb. 12 Morbidity and Mortality Weekly Report, the CDC describes the mumps outbreak, which began in a New York summer camp for tradition-observant Jewish boys and has spread substantially among members of tradition-observant Jewish communities in New York City, New Jersey, and two counties in upstate New York. The majority of the affected patients have been boys older than 6 years (median age, 15 years, among those whose age is known). To date, there have been 65 reports of mumps-related complications, 19 mumps-related hospitalizations, and no deaths, according to the report (MMWR 2010;59:125-9).

An assessment of MMR vaccination status, which was known in 1,115 of the cases, showed that 976 patients had received at least one dose before the outbreak and 839 had received two doses. This finding emphasizes the fact that mumps outbreaks can occur in highly vaccinated populations, which is likely attributable, in part, to the fact that the effectiveness of the mumps component of the MMR vaccine is lower than that of the measles and rubella components, according to an editorial note in the report. For this reason, public health officials in Orange County, N.Y., where transmission continued among students in three religious schools, despite high two-dose coverage, began offering a third MMR dose to students in the schools.

To date, “no data exist on the effectiveness of a third dose in either reducing the risk for mumps or altering the course of an outbreak,” nor has the CDC's Advisory Committee on Immunization Practices recommended a third dose, the authors stated. However, they noted, “a previous study indicated that a third dose of MMR vaccine for seronegative college students resulted in rapid seroconversion with a low rate of IgM response, which is indicative of an anamnestic immune response” (J. Infect. Dis. 2008;197:1662-8).

The authors hypothesized that the settings in which the outbreaks occurred—predominantly all-boys' schools where students spend long periods in large study halls and are often face to face with a study partner—and the relatively large household sizes of the affected community might be facilitating transmission within the community and limiting transmission outside it. They stress, however, that “the high vaccination coverage in the affected community likely is limiting the size of the outbreak.”

Additionally, high vaccination coverage outside the community might explain why the few cases that have occurred outside the community have not led to new outbreaks, the authors wrote.

While maintaining high MMR vaccination coverage doesn't prevent all mumps outbreaks, it remains the most effective preventive measure available, thus timely vaccination with two doses should be encouraged, according to the report.

The authors also advocated a high degree of awareness among health care providers that mumps can occur in areas of high vaccination coverage. Providers are urged to promptly report cases of mumps and isolate individuals with suspected or confirmed disease for 5 days after onset.