Nancy Walsh

BOSTON — Prehypertensive patients who participate in a structured weight-management program can significantly cut their risk factors and may avoid the need for drug therapy, according to a study presented at the annual meeting of NAASO, the Obesity Society.

A group of 351 patients who enrolled in various weight-loss programs had a mean baseline BP of 127/83 mm Hg. Over an average follow-up period of just under 3 years, these readings fell to a mean of 119/74 mm Hg, reported Linda Grant of Health Management Resources (HMR), Boston.

Mean weight at baseline was 231 pounds. During the follow-up period, this fell to 194 pounds, representing an average of 16% of initial body weight lost.

None of the patients was taking antihypertensive medications at baseline, and about 94 remained medication free throughout the study.

Patients in this cohort also had significant decreases in all other measured risk factors. Total cholesterol levels fell by an average of 14%, triglycerides decreased by 30%, and fasting blood glucose was lowered by 5%, Ms. Grant wrote in a poster session. “Lifestyle changes, including weight management, should be the first step in preventing or delaying the progression of prehypertension to hypertension and in reducing other comorbid risk factors,” she wrote.

The weight-management options offered by HMR include medically supervised low- and very-low-calorie diets, moderately restricted diets, and telephone-based programs. All of the options focus on lifestyle changes such as increased physical activity to an expenditure of 2,000 kcal/week or more, the use of meal replacements, and increased fruit and vegetable intake to 35 servings/week or more.

In another study undertaken by HMR, Steve May, Ph.D., reported that program participants who lost 20% or more of their body weight had greater decreases in risk factors than did those who lost smaller amounts of weight.

Among 2,564 patients who had participated in the HMR weight-management programs at 65 clinics natiowide, those who lost the most weight—and kept it off for an average time of 123 weeks—also showed significant decreases in all other measured risk factors.

Moreover, a significant percentage of patients were able to eliminate medications for cholesterol, BP, and diabetes, Dr. May wrote.

BOSTON — Prehypertensive patients who participate in a structured weight-management program can significantly cut their risk factors and may avoid the need for drug therapy, according to a study presented at the annual meeting of NAASO, the Obesity Society.

A group of 351 patients who enrolled in various weight-loss programs had a mean baseline BP of 127/83 mm Hg. Over an average follow-up period of just under 3 years, these readings fell to a mean of 119/74 mm Hg, reported Linda Grant of Health Management Resources (HMR), Boston.

Mean weight at baseline was 231 pounds. During the follow-up period, this fell to 194 pounds, representing an average of 16% of initial body weight lost.

None of the patients was taking antihypertensive medications at baseline, and about 94 remained medication free throughout the study.

Patients in this cohort also had significant decreases in all other measured risk factors. Total cholesterol levels fell by an average of 14%, triglycerides decreased by 30%, and fasting blood glucose was lowered by 5%, Ms. Grant wrote in a poster session. “Lifestyle changes, including weight management, should be the first step in preventing or delaying the progression of prehypertension to hypertension and in reducing other comorbid risk factors,” she wrote.

The weight-management options offered by HMR include medically supervised low- and very-low-calorie diets, moderately restricted diets, and telephone-based programs. All of the options focus on lifestyle changes such as increased physical activity to an expenditure of 2,000 kcal/week or more, the use of meal replacements, and increased fruit and vegetable intake to 35 servings/week or more.

In another study undertaken by HMR, Steve May, Ph.D., reported that program participants who lost 20% or more of their body weight had greater decreases in risk factors than did those who lost smaller amounts of weight.

Among 2,564 patients who had participated in the HMR weight-management programs at 65 clinics natiowide, those who lost the most weight—and kept it off for an average time of 123 weeks—also showed significant decreases in all other measured risk factors.

Moreover, a significant percentage of patients were able to eliminate medications for cholesterol, BP, and diabetes, Dr. May wrote.

BOSTON — Prehypertensive patients who participate in a structured weight-management program can significantly cut their risk factors and may avoid the need for drug therapy, according to a study presented at the annual meeting of NAASO, the Obesity Society.

A group of 351 patients who enrolled in various weight-loss programs had a mean baseline BP of 127/83 mm Hg. Over an average follow-up period of just under 3 years, these readings fell to a mean of 119/74 mm Hg, reported Linda Grant of Health Management Resources (HMR), Boston.

Mean weight at baseline was 231 pounds. During the follow-up period, this fell to 194 pounds, representing an average of 16% of initial body weight lost.

None of the patients was taking antihypertensive medications at baseline, and about 94 remained medication free throughout the study.

Patients in this cohort also had significant decreases in all other measured risk factors. Total cholesterol levels fell by an average of 14%, triglycerides decreased by 30%, and fasting blood glucose was lowered by 5%, Ms. Grant wrote in a poster session. “Lifestyle changes, including weight management, should be the first step in preventing or delaying the progression of prehypertension to hypertension and in reducing other comorbid risk factors,” she wrote.

The weight-management options offered by HMR include medically supervised low- and very-low-calorie diets, moderately restricted diets, and telephone-based programs. All of the options focus on lifestyle changes such as increased physical activity to an expenditure of 2,000 kcal/week or more, the use of meal replacements, and increased fruit and vegetable intake to 35 servings/week or more.

In another study undertaken by HMR, Steve May, Ph.D., reported that program participants who lost 20% or more of their body weight had greater decreases in risk factors than did those who lost smaller amounts of weight.

Among 2,564 patients who had participated in the HMR weight-management programs at 65 clinics natiowide, those who lost the most weight—and kept it off for an average time of 123 weeks—also showed significant decreases in all other measured risk factors.

Moreover, a significant percentage of patients were able to eliminate medications for cholesterol, BP, and diabetes, Dr. May wrote.

Admission to a neonatal intensive care unit before July 1992 should be considered a risk factor for hepatitis C virus infection because patients may have received tainted transfusions, results of a new study suggest.

Among the estimated 3.9 million Americans infected with hepatitis C virus (HCV), approximately 7% are thought to have acquired the virus through transfusion before blood banks implemented screening with the second-generation HCV antibody enzyme immunoassay. Neonates who required care in the neonatal intensive care unit (NICU) before screening became available represent an unquantified but potentially significant segment of the at-risk population because of their likelihood for having received multiple transfusions, according to Henry H. Cagle and his colleagues from the Liver Disease and Hepatitis Program of the Alaska Native Tribal Health Consortium and the Providence Alaska Medical Center, Anchorage (Arch. Pediatr. Adolesc. Med. 2007;161:125–30).

To address this concern, they undertook a lookback program aimed at identifying transfusion recipients and providing them with information about HCV testing.

A total of 1,797 patients were identified through a search of records from the NICU at Providence Alaska Medical Center. Of these, 401 were from an integrated, managed care type system at Alaska Native Medical Center (ANMC) and 1,396 were from the private sector.

Letters were mailed to the 277 ANMC patients who could be located and to the 374 private-sector patients for whom contact information was available. The proportion of private-sector patients who could not be located (60%) was significantly higher than that of ANMC patients who could not be found (16%).

Among the 151 ANMC patients who responded and underwent HCV testing, 6 (4%) were anti-HCV positive, while among the 64 private-sector patients who responded and were tested, 1 (2%) was positive.

The difference in the researchers' ability to locate patients from ANMC and from the private sector was related to the fact that for most patients in the integrated system there was a continuous medical record that included information about name changes relating to adoption or marriage, according to the authors. They noted that 51% of the patients or their parents were unaware that the patient had received blood products, possibly because at the time consent was not required. In addition, parents—because of the high degree of parental stress associated with NICU admission—may have simply forgotten.

The investigators concluded that because such a large proportion of patients were unaware of their transfusion history and potential for infection, a history of NICU admission should be considered a risk factor for HCV and that it would be “prudent” for health care professionals to screen any such patients for infection.

In an accompanying editorial, Dr. Maureen M. Jonas of Children's Hospital, Boston, noted that children and adolescents do not routinely donate blood or have routine blood tests that might reveal liver abnormalities. She noted that identification of infected patients would provide an opportunity for counseling regarding other risk factors such as alcohol consumption and the use of hepatotoxic medications. Younger patients also might be better able to tolerate the demanding treatment regimen, she wrote (Arch. Pediatr. Adolesc. Med. 2007;161:202–3).

Admission to a neonatal intensive care unit before July 1992 should be considered a risk factor for hepatitis C virus infection because patients may have received tainted transfusions, results of a new study suggest.

Among the estimated 3.9 million Americans infected with hepatitis C virus (HCV), approximately 7% are thought to have acquired the virus through transfusion before blood banks implemented screening with the second-generation HCV antibody enzyme immunoassay. Neonates who required care in the neonatal intensive care unit (NICU) before screening became available represent an unquantified but potentially significant segment of the at-risk population because of their likelihood for having received multiple transfusions, according to Henry H. Cagle and his colleagues from the Liver Disease and Hepatitis Program of the Alaska Native Tribal Health Consortium and the Providence Alaska Medical Center, Anchorage (Arch. Pediatr. Adolesc. Med. 2007;161:125–30).

To address this concern, they undertook a lookback program aimed at identifying transfusion recipients and providing them with information about HCV testing.

A total of 1,797 patients were identified through a search of records from the NICU at Providence Alaska Medical Center. Of these, 401 were from an integrated, managed care type system at Alaska Native Medical Center (ANMC) and 1,396 were from the private sector.

Letters were mailed to the 277 ANMC patients who could be located and to the 374 private-sector patients for whom contact information was available. The proportion of private-sector patients who could not be located (60%) was significantly higher than that of ANMC patients who could not be found (16%).

Among the 151 ANMC patients who responded and underwent HCV testing, 6 (4%) were anti-HCV positive, while among the 64 private-sector patients who responded and were tested, 1 (2%) was positive.

The difference in the researchers' ability to locate patients from ANMC and from the private sector was related to the fact that for most patients in the integrated system there was a continuous medical record that included information about name changes relating to adoption or marriage, according to the authors. They noted that 51% of the patients or their parents were unaware that the patient had received blood products, possibly because at the time consent was not required. In addition, parents—because of the high degree of parental stress associated with NICU admission—may have simply forgotten.

The investigators concluded that because such a large proportion of patients were unaware of their transfusion history and potential for infection, a history of NICU admission should be considered a risk factor for HCV and that it would be “prudent” for health care professionals to screen any such patients for infection.

In an accompanying editorial, Dr. Maureen M. Jonas of Children's Hospital, Boston, noted that children and adolescents do not routinely donate blood or have routine blood tests that might reveal liver abnormalities. She noted that identification of infected patients would provide an opportunity for counseling regarding other risk factors such as alcohol consumption and the use of hepatotoxic medications. Younger patients also might be better able to tolerate the demanding treatment regimen, she wrote (Arch. Pediatr. Adolesc. Med. 2007;161:202–3).

Admission to a neonatal intensive care unit before July 1992 should be considered a risk factor for hepatitis C virus infection because patients may have received tainted transfusions, results of a new study suggest.

Among the estimated 3.9 million Americans infected with hepatitis C virus (HCV), approximately 7% are thought to have acquired the virus through transfusion before blood banks implemented screening with the second-generation HCV antibody enzyme immunoassay. Neonates who required care in the neonatal intensive care unit (NICU) before screening became available represent an unquantified but potentially significant segment of the at-risk population because of their likelihood for having received multiple transfusions, according to Henry H. Cagle and his colleagues from the Liver Disease and Hepatitis Program of the Alaska Native Tribal Health Consortium and the Providence Alaska Medical Center, Anchorage (Arch. Pediatr. Adolesc. Med. 2007;161:125–30).

To address this concern, they undertook a lookback program aimed at identifying transfusion recipients and providing them with information about HCV testing.

A total of 1,797 patients were identified through a search of records from the NICU at Providence Alaska Medical Center. Of these, 401 were from an integrated, managed care type system at Alaska Native Medical Center (ANMC) and 1,396 were from the private sector.

Letters were mailed to the 277 ANMC patients who could be located and to the 374 private-sector patients for whom contact information was available. The proportion of private-sector patients who could not be located (60%) was significantly higher than that of ANMC patients who could not be found (16%).

Among the 151 ANMC patients who responded and underwent HCV testing, 6 (4%) were anti-HCV positive, while among the 64 private-sector patients who responded and were tested, 1 (2%) was positive.

The difference in the researchers' ability to locate patients from ANMC and from the private sector was related to the fact that for most patients in the integrated system there was a continuous medical record that included information about name changes relating to adoption or marriage, according to the authors. They noted that 51% of the patients or their parents were unaware that the patient had received blood products, possibly because at the time consent was not required. In addition, parents—because of the high degree of parental stress associated with NICU admission—may have simply forgotten.

The investigators concluded that because such a large proportion of patients were unaware of their transfusion history and potential for infection, a history of NICU admission should be considered a risk factor for HCV and that it would be “prudent” for health care professionals to screen any such patients for infection.

In an accompanying editorial, Dr. Maureen M. Jonas of Children's Hospital, Boston, noted that children and adolescents do not routinely donate blood or have routine blood tests that might reveal liver abnormalities. She noted that identification of infected patients would provide an opportunity for counseling regarding other risk factors such as alcohol consumption and the use of hepatotoxic medications. Younger patients also might be better able to tolerate the demanding treatment regimen, she wrote (Arch. Pediatr. Adolesc. Med. 2007;161:202–3).

The availability of more effective arthritis drugs and monitoring techniques has created a critical window of opportunity when joint destruction can be averted and function maintained. To help clinicians make the most of this crucial period in management of the disease, an expert committee of the European League Against Rheumatism has written new guidelines on optimal management of early arthritis.

Among the issues addressed by the guidelines are the need for accurate, prompt diagnosis and the early institution of disease-modifying antirheumatic drug (DMARD) therapy and, if appropriate, nonsteroidal anti-inflammatory agents and corticosteroids (Ann. Rheum. Dis. 2007;66:34–45). They also provide guidance on monitoring and nonpharmaceutic adjuncts to treatment, and set out an agenda for further research.

The recommendations, which are based on evidence in the literature as well as expert consensus, are as follows:

▸ Patients presenting with arthritis of more than one joint should be referred to a rheumatologist, if possible within 6 weeks of symptom onset.

▸ Clinical examination is the method of choice for diagnosis, although imaging studies with ultrasound and MRI can be helpful when there is uncertainty.

▸ A careful history is needed to rule out other diagnoses, along with laboratory tests including complete blood cell count, urinalysis, measurement of transaminases, and detection of antinuclear antibodies.

▸ All patients with early arthritis should be evaluated for factors that are predictive of persistent and erosive disease, including number of swollen and tender joints, erythrocyte sedimentation rate or C-reactive protein, rheumatoid factor, anticyclic citrullinated peptide antibodies, and radiographic erosions.

▸ Patients at risk for persistent or erosive disease should begin therapy with DMARDs even if their arthritis remains undifferentiated.

▸ Educational measures may be employed adjunctively to help patients deal with pain and disability.

▸ Nonsteroidal anti-inflammatory drugs can be considered for symptomatic relief, with consideration given to potential adverse gastrointestinal, renal, and cardiovascular effects.

▸ Systemic corticosteroids can be used in addition to DMARDs, generally in a temporary fashion, and intra-articular corticosteroid injections should be considered for local symptomatic inflammation.

▸ Methotrexate is considered the “anchor” DMARD, with leflunomide and sulfasalazine as alternatives when necessary.

▸ The goal of DMARD therapy is remission, and monitoring should guide treatment decisions and strategy changes as needed.

▸ Nonpharmaceutic interventions such as exercise can be helpful in improving strength and physical function in patients with early arthritis.

▸ Routine monitoring during early disease should include tender and swollen joint counts, patient and physician global assessment, and measurement of erythrocyte sedimentation rate and C-reactive protein, and structural damage should be monitored by x-rays every 6–12 months.

The availability of more effective arthritis drugs and monitoring techniques has created a critical window of opportunity when joint destruction can be averted and function maintained. To help clinicians make the most of this crucial period in management of the disease, an expert committee of the European League Against Rheumatism has written new guidelines on optimal management of early arthritis.

Among the issues addressed by the guidelines are the need for accurate, prompt diagnosis and the early institution of disease-modifying antirheumatic drug (DMARD) therapy and, if appropriate, nonsteroidal anti-inflammatory agents and corticosteroids (Ann. Rheum. Dis. 2007;66:34–45). They also provide guidance on monitoring and nonpharmaceutic adjuncts to treatment, and set out an agenda for further research.

The recommendations, which are based on evidence in the literature as well as expert consensus, are as follows:

▸ Patients presenting with arthritis of more than one joint should be referred to a rheumatologist, if possible within 6 weeks of symptom onset.

▸ Clinical examination is the method of choice for diagnosis, although imaging studies with ultrasound and MRI can be helpful when there is uncertainty.

▸ A careful history is needed to rule out other diagnoses, along with laboratory tests including complete blood cell count, urinalysis, measurement of transaminases, and detection of antinuclear antibodies.

▸ All patients with early arthritis should be evaluated for factors that are predictive of persistent and erosive disease, including number of swollen and tender joints, erythrocyte sedimentation rate or C-reactive protein, rheumatoid factor, anticyclic citrullinated peptide antibodies, and radiographic erosions.

▸ Patients at risk for persistent or erosive disease should begin therapy with DMARDs even if their arthritis remains undifferentiated.

▸ Educational measures may be employed adjunctively to help patients deal with pain and disability.

▸ Nonsteroidal anti-inflammatory drugs can be considered for symptomatic relief, with consideration given to potential adverse gastrointestinal, renal, and cardiovascular effects.

▸ Systemic corticosteroids can be used in addition to DMARDs, generally in a temporary fashion, and intra-articular corticosteroid injections should be considered for local symptomatic inflammation.

▸ Methotrexate is considered the “anchor” DMARD, with leflunomide and sulfasalazine as alternatives when necessary.

▸ The goal of DMARD therapy is remission, and monitoring should guide treatment decisions and strategy changes as needed.

▸ Nonpharmaceutic interventions such as exercise can be helpful in improving strength and physical function in patients with early arthritis.

▸ Routine monitoring during early disease should include tender and swollen joint counts, patient and physician global assessment, and measurement of erythrocyte sedimentation rate and C-reactive protein, and structural damage should be monitored by x-rays every 6–12 months.

The availability of more effective arthritis drugs and monitoring techniques has created a critical window of opportunity when joint destruction can be averted and function maintained. To help clinicians make the most of this crucial period in management of the disease, an expert committee of the European League Against Rheumatism has written new guidelines on optimal management of early arthritis.

Among the issues addressed by the guidelines are the need for accurate, prompt diagnosis and the early institution of disease-modifying antirheumatic drug (DMARD) therapy and, if appropriate, nonsteroidal anti-inflammatory agents and corticosteroids (Ann. Rheum. Dis. 2007;66:34–45). They also provide guidance on monitoring and nonpharmaceutic adjuncts to treatment, and set out an agenda for further research.

The recommendations, which are based on evidence in the literature as well as expert consensus, are as follows:

▸ Patients presenting with arthritis of more than one joint should be referred to a rheumatologist, if possible within 6 weeks of symptom onset.

▸ Clinical examination is the method of choice for diagnosis, although imaging studies with ultrasound and MRI can be helpful when there is uncertainty.

▸ A careful history is needed to rule out other diagnoses, along with laboratory tests including complete blood cell count, urinalysis, measurement of transaminases, and detection of antinuclear antibodies.

▸ All patients with early arthritis should be evaluated for factors that are predictive of persistent and erosive disease, including number of swollen and tender joints, erythrocyte sedimentation rate or C-reactive protein, rheumatoid factor, anticyclic citrullinated peptide antibodies, and radiographic erosions.

▸ Patients at risk for persistent or erosive disease should begin therapy with DMARDs even if their arthritis remains undifferentiated.

▸ Educational measures may be employed adjunctively to help patients deal with pain and disability.

▸ Nonsteroidal anti-inflammatory drugs can be considered for symptomatic relief, with consideration given to potential adverse gastrointestinal, renal, and cardiovascular effects.

▸ Systemic corticosteroids can be used in addition to DMARDs, generally in a temporary fashion, and intra-articular corticosteroid injections should be considered for local symptomatic inflammation.

▸ Methotrexate is considered the “anchor” DMARD, with leflunomide and sulfasalazine as alternatives when necessary.

▸ The goal of DMARD therapy is remission, and monitoring should guide treatment decisions and strategy changes as needed.

▸ Nonpharmaceutic interventions such as exercise can be helpful in improving strength and physical function in patients with early arthritis.

▸ Routine monitoring during early disease should include tender and swollen joint counts, patient and physician global assessment, and measurement of erythrocyte sedimentation rate and C-reactive protein, and structural damage should be monitored by x-rays every 6–12 months.

WASHINGTON — Treatment with glucocorticoids was strongly associated with the presence of coronary calcification among patients with rheumatoid arthritis in a cross-sectional analysis, Dr. Jon T. Giles reported at the annual meeting of the American College of Rheumatology.

Coronary artery calcification, as measured by high-resolution computed tomography, is a quantifiable representation of coronary atherosclerotic burden and is predictive of future cardiovascular events in patients with subclinical atherosclerosis, according to Dr. Giles of Johns Hopkins University, Baltimore.

A group of 187 patients (115 women), underwent multidetector-row computed tomography of the chest with quantification of coronary artery calcification using the Agatston scoring method. The overall prevalence of calcification was 53%, and among men of all ages, it was 75% and among women, 39%.

Patients also underwent laboratory assessments including those for fasting glucose, cholesterol, triglycerides, C-reactive protein, and homocysteine. Data were collected on demographics, body composition, and medication history, and functional status was evaluated on the health assessment questionnaire (HAQ). Depression was rated on the basis of a Center for Epidemiologic Study depression score. A multivariate logistic regression analysis determined the association of individual characteristics with the presence of coronary artery calcification.

After controlling for demographic and conventional risk factors, the presence of any coronary artery calcification was significantly associated with increased levels of clinical depression (odds ratio 1.05), HAQ score (OR 1.71), and high waist:hip ratio (OR 1.21). Most notable was that when compared with no exposure, any history of glucocorticoid exposure was associated with an odds ratio of 2.98 for calcification, even after adjusting for demographic and cardiovascular risk factors, Dr. Giles wrote in a poster session.

Rheumatoid arthritis disease duration and current disease activity such as C-reactive protein were not associated with calcification, while increased education was associated with a decreased odds ratio of 0.71.

“These data would suggest that careful [use] of glucocorticoids in the clinical setting, avoidance of central obesity, and efforts to improve physical functioning and to promote psychological well-being … may be effective strategies in reducing the burden of atherosclerosis in RA patients,” he concluded.

WASHINGTON — Treatment with glucocorticoids was strongly associated with the presence of coronary calcification among patients with rheumatoid arthritis in a cross-sectional analysis, Dr. Jon T. Giles reported at the annual meeting of the American College of Rheumatology.

Coronary artery calcification, as measured by high-resolution computed tomography, is a quantifiable representation of coronary atherosclerotic burden and is predictive of future cardiovascular events in patients with subclinical atherosclerosis, according to Dr. Giles of Johns Hopkins University, Baltimore.

A group of 187 patients (115 women), underwent multidetector-row computed tomography of the chest with quantification of coronary artery calcification using the Agatston scoring method. The overall prevalence of calcification was 53%, and among men of all ages, it was 75% and among women, 39%.

Patients also underwent laboratory assessments including those for fasting glucose, cholesterol, triglycerides, C-reactive protein, and homocysteine. Data were collected on demographics, body composition, and medication history, and functional status was evaluated on the health assessment questionnaire (HAQ). Depression was rated on the basis of a Center for Epidemiologic Study depression score. A multivariate logistic regression analysis determined the association of individual characteristics with the presence of coronary artery calcification.

After controlling for demographic and conventional risk factors, the presence of any coronary artery calcification was significantly associated with increased levels of clinical depression (odds ratio 1.05), HAQ score (OR 1.71), and high waist:hip ratio (OR 1.21). Most notable was that when compared with no exposure, any history of glucocorticoid exposure was associated with an odds ratio of 2.98 for calcification, even after adjusting for demographic and cardiovascular risk factors, Dr. Giles wrote in a poster session.

Rheumatoid arthritis disease duration and current disease activity such as C-reactive protein were not associated with calcification, while increased education was associated with a decreased odds ratio of 0.71.

“These data would suggest that careful [use] of glucocorticoids in the clinical setting, avoidance of central obesity, and efforts to improve physical functioning and to promote psychological well-being … may be effective strategies in reducing the burden of atherosclerosis in RA patients,” he concluded.

WASHINGTON — Treatment with glucocorticoids was strongly associated with the presence of coronary calcification among patients with rheumatoid arthritis in a cross-sectional analysis, Dr. Jon T. Giles reported at the annual meeting of the American College of Rheumatology.

Coronary artery calcification, as measured by high-resolution computed tomography, is a quantifiable representation of coronary atherosclerotic burden and is predictive of future cardiovascular events in patients with subclinical atherosclerosis, according to Dr. Giles of Johns Hopkins University, Baltimore.

A group of 187 patients (115 women), underwent multidetector-row computed tomography of the chest with quantification of coronary artery calcification using the Agatston scoring method. The overall prevalence of calcification was 53%, and among men of all ages, it was 75% and among women, 39%.

Patients also underwent laboratory assessments including those for fasting glucose, cholesterol, triglycerides, C-reactive protein, and homocysteine. Data were collected on demographics, body composition, and medication history, and functional status was evaluated on the health assessment questionnaire (HAQ). Depression was rated on the basis of a Center for Epidemiologic Study depression score. A multivariate logistic regression analysis determined the association of individual characteristics with the presence of coronary artery calcification.

After controlling for demographic and conventional risk factors, the presence of any coronary artery calcification was significantly associated with increased levels of clinical depression (odds ratio 1.05), HAQ score (OR 1.71), and high waist:hip ratio (OR 1.21). Most notable was that when compared with no exposure, any history of glucocorticoid exposure was associated with an odds ratio of 2.98 for calcification, even after adjusting for demographic and cardiovascular risk factors, Dr. Giles wrote in a poster session.

Rheumatoid arthritis disease duration and current disease activity such as C-reactive protein were not associated with calcification, while increased education was associated with a decreased odds ratio of 0.71.

“These data would suggest that careful [use] of glucocorticoids in the clinical setting, avoidance of central obesity, and efforts to improve physical functioning and to promote psychological well-being … may be effective strategies in reducing the burden of atherosclerosis in RA patients,” he concluded.

WASHINGTON — Early functional disability is predictive of all-cause and cardiovascular mortality in patients with inflammatory polyarthritis, Dr. Tracey M. Farragher reported at the annual meeting of the American College of Rheumatology.

An association between early functional disability, as measured by the Health Assessment Questionnaire (HAQ), and later mortality has previously been noted. But whether the baseline HAQ score or the HAQ score at 1 year, at which time disease modifying antirheumatic drug (DMARD) therapy is likely to have been initiated, represents a more accurate predictor of mortality has not previously been investigated, according to Dr. Farragher of the University of Manchester (England).

But now, analysis of longitudinal data from the Norfolk (England) Arthritis Register has determined that HAQ score at 1 year is a stronger predictor of mortality, particularly from cardiovascular causes, than is baseline HAQ score.

The register enrolled 1,010 patients with new-onset inflammatory polyarthritis between 1990 and 1994. They were assessed at 1, 5, 7, and 10 years, with structured interviews and clinical examinations. Patients were stratified according to HAQ score as being less than 1 (none or mild disability), 1–2 (moderate disability), or greater than 2 (severe disability).

By 1 year, 40% of the patients had been treated with a DMARD, which was reflected in changes in HAQ scores: In the 590 patients in the group with the lowest HAQ scores, the median swollen and tender joint count was one at baseline and none at year 1. In the 331 in the moderate HAQ group, the median swollen and tender joint counts were 6 at baseline and 2 at year 1, and in the 89 in the severe HAQ group, these counts were 10.5 at baseline and 5 at year 1.

Mortality rates per 1,000 person-years were calculated according to HAQ scores, and information on numbers and causes of death was obtained by the Office for National Statistics. By the end of 10 years, 170 patients had died, 69 (41%) of cardiovascular causes, with the highest mortality rates in the severe HAQ group at both time points.

The increase in the all-cause mortality rate per unit increase in HAQ score was about 25% greater using the 1-year score rather than the baseline score, Dr. Farragher wrote in a poster session. The hazard ratio for all deaths at baseline was 1.32, compared with 1.61 at year 1. The corresponding numbers for cardiovascular deaths were 1.29 and 1.96.

The 1-year HAQ score is a marker of residual disease activity and, by implication, physical activity, which may account for its predictive capacity for cardiovascular disease and mortality, wrote Dr. Farragher and her colleagues (Ann. Rheum. Dis. 2006 Nov 7 [Epub doi:10.1136/ard.2006.056390]).

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Early functional disability is predictive of all-cause and cardiovascular mortality in patients with inflammatory polyarthritis, Dr. Tracey M. Farragher reported at the annual meeting of the American College of Rheumatology.

An association between early functional disability, as measured by the Health Assessment Questionnaire (HAQ), and later mortality has previously been noted. But whether the baseline HAQ score or the HAQ score at 1 year, at which time disease modifying antirheumatic drug (DMARD) therapy is likely to have been initiated, represents a more accurate predictor of mortality has not previously been investigated, according to Dr. Farragher of the University of Manchester (England).

But now, analysis of longitudinal data from the Norfolk (England) Arthritis Register has determined that HAQ score at 1 year is a stronger predictor of mortality, particularly from cardiovascular causes, than is baseline HAQ score.

The register enrolled 1,010 patients with new-onset inflammatory polyarthritis between 1990 and 1994. They were assessed at 1, 5, 7, and 10 years, with structured interviews and clinical examinations. Patients were stratified according to HAQ score as being less than 1 (none or mild disability), 1–2 (moderate disability), or greater than 2 (severe disability).

By 1 year, 40% of the patients had been treated with a DMARD, which was reflected in changes in HAQ scores: In the 590 patients in the group with the lowest HAQ scores, the median swollen and tender joint count was one at baseline and none at year 1. In the 331 in the moderate HAQ group, the median swollen and tender joint counts were 6 at baseline and 2 at year 1, and in the 89 in the severe HAQ group, these counts were 10.5 at baseline and 5 at year 1.

Mortality rates per 1,000 person-years were calculated according to HAQ scores, and information on numbers and causes of death was obtained by the Office for National Statistics. By the end of 10 years, 170 patients had died, 69 (41%) of cardiovascular causes, with the highest mortality rates in the severe HAQ group at both time points.

The increase in the all-cause mortality rate per unit increase in HAQ score was about 25% greater using the 1-year score rather than the baseline score, Dr. Farragher wrote in a poster session. The hazard ratio for all deaths at baseline was 1.32, compared with 1.61 at year 1. The corresponding numbers for cardiovascular deaths were 1.29 and 1.96.

The 1-year HAQ score is a marker of residual disease activity and, by implication, physical activity, which may account for its predictive capacity for cardiovascular disease and mortality, wrote Dr. Farragher and her colleagues (Ann. Rheum. Dis. 2006 Nov 7 [Epub doi:10.1136/ard.2006.056390]).

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Early functional disability is predictive of all-cause and cardiovascular mortality in patients with inflammatory polyarthritis, Dr. Tracey M. Farragher reported at the annual meeting of the American College of Rheumatology.

An association between early functional disability, as measured by the Health Assessment Questionnaire (HAQ), and later mortality has previously been noted. But whether the baseline HAQ score or the HAQ score at 1 year, at which time disease modifying antirheumatic drug (DMARD) therapy is likely to have been initiated, represents a more accurate predictor of mortality has not previously been investigated, according to Dr. Farragher of the University of Manchester (England).

But now, analysis of longitudinal data from the Norfolk (England) Arthritis Register has determined that HAQ score at 1 year is a stronger predictor of mortality, particularly from cardiovascular causes, than is baseline HAQ score.

The register enrolled 1,010 patients with new-onset inflammatory polyarthritis between 1990 and 1994. They were assessed at 1, 5, 7, and 10 years, with structured interviews and clinical examinations. Patients were stratified according to HAQ score as being less than 1 (none or mild disability), 1–2 (moderate disability), or greater than 2 (severe disability).

By 1 year, 40% of the patients had been treated with a DMARD, which was reflected in changes in HAQ scores: In the 590 patients in the group with the lowest HAQ scores, the median swollen and tender joint count was one at baseline and none at year 1. In the 331 in the moderate HAQ group, the median swollen and tender joint counts were 6 at baseline and 2 at year 1, and in the 89 in the severe HAQ group, these counts were 10.5 at baseline and 5 at year 1.

Mortality rates per 1,000 person-years were calculated according to HAQ scores, and information on numbers and causes of death was obtained by the Office for National Statistics. By the end of 10 years, 170 patients had died, 69 (41%) of cardiovascular causes, with the highest mortality rates in the severe HAQ group at both time points.

The increase in the all-cause mortality rate per unit increase in HAQ score was about 25% greater using the 1-year score rather than the baseline score, Dr. Farragher wrote in a poster session. The hazard ratio for all deaths at baseline was 1.32, compared with 1.61 at year 1. The corresponding numbers for cardiovascular deaths were 1.29 and 1.96.

The 1-year HAQ score is a marker of residual disease activity and, by implication, physical activity, which may account for its predictive capacity for cardiovascular disease and mortality, wrote Dr. Farragher and her colleagues (Ann. Rheum. Dis. 2006 Nov 7 [Epub doi:10.1136/ard.2006.056390]).

ELSEVIER GLOBAL MEDICAL NEWS

LA JOLLA, CALIF. — The newly enacted Dietary Supplement and Nonprescription Drug Consumer Protection Act mandates for the first time the reporting of serious adverse events associated with dietary supplements and over-the-counter products.

The law, passed by Congress in December, is the first revision of the regulation of dietary supplements since the passage of the Dietary Supplement Health and Education Act (DSHEA) of 1994, Peter Reinecke said at a symposium on natural supplements sponsored by the Scripps Center for Integrative Medicine.

DSHEA authorized the Food and Drug Administration (FDA) to seize products that are adulterated or misbranded and to remove from the market products that present significant or unreasonable risk of injury or illness or that pose an imminent hazard to public health or safety. It made no provision for the same type of reporting of adverse events that is required for pharmaceutical drugs.

But when the new law goes into effect on Dec. 22, 2007, all manufacturers, packers, and distributors of supplements will be required to report serious adverse events to the FDA within 15 business days through the MedWatch program.

Serious adverse events are defined as those that result in death, a life-threatening experience, inpatient hospitalization, persistent or significant disability or incapacity, or a congenital abnormality or birth defect; or that require, based on reasonable medical judgment, a medical or surgical intervention to prevent one of these outcomes.

If a consumer reports that he or she has experienced a serious adverse event, the manufacturer must report it–regardless of whether proof is provided, medical care was sought, or the company disagrees with the claim.

“The intent of the new law is clearly to err on the side of over-reporting to give the FDA the ability to spot trends that are out there, not to overanalyze any single event,” explained Mr. Reinecke, principal of Reinecke Strategic Solutions, Bethesda, Md.

The labeling of dietary supplements will be required to include an address or telephone number consumers can use to contact the manufacturer or other responsible party, should an adverse event occur.

Any product without this informaton on the label will be considered misbranded, Mr. Reinecke said at the meeting, which was cosponsored by the University of California, San Diego.

Manufacturers, packers, and distributors will be required to maintain for 6 years all records relating to adverse event reports.

Falsification of any records will be illegal, and could lead to an injunction or criminal penalties.

The recent change of leadership in Congress is likely to result in greater efforts to ensure the safety of supplements, particularly by implementing and making final the DSHEA provision that establishes good manufacturing practices governing the preparation, packing, and holding of these products, said Mr. Reinecke, who was one of the Capitol Hill staffers involved in writing DSHEA.

“This provision is long overdue and greatly needed,” he said.

“The coming year also is likely to see the biggest effort in Washington in the 20-something years I've been there to get the FDA some much-needed resources. This will be difficult given the fiscal situation in which we find ourselves, but there is strong support for this in industry and consumer groups,” he said.

LA JOLLA, CALIF. — The newly enacted Dietary Supplement and Nonprescription Drug Consumer Protection Act mandates for the first time the reporting of serious adverse events associated with dietary supplements and over-the-counter products.

The law, passed by Congress in December, is the first revision of the regulation of dietary supplements since the passage of the Dietary Supplement Health and Education Act (DSHEA) of 1994, Peter Reinecke said at a symposium on natural supplements sponsored by the Scripps Center for Integrative Medicine.

DSHEA authorized the Food and Drug Administration (FDA) to seize products that are adulterated or misbranded and to remove from the market products that present significant or unreasonable risk of injury or illness or that pose an imminent hazard to public health or safety. It made no provision for the same type of reporting of adverse events that is required for pharmaceutical drugs.

But when the new law goes into effect on Dec. 22, 2007, all manufacturers, packers, and distributors of supplements will be required to report serious adverse events to the FDA within 15 business days through the MedWatch program.

Serious adverse events are defined as those that result in death, a life-threatening experience, inpatient hospitalization, persistent or significant disability or incapacity, or a congenital abnormality or birth defect; or that require, based on reasonable medical judgment, a medical or surgical intervention to prevent one of these outcomes.

If a consumer reports that he or she has experienced a serious adverse event, the manufacturer must report it–regardless of whether proof is provided, medical care was sought, or the company disagrees with the claim.

“The intent of the new law is clearly to err on the side of over-reporting to give the FDA the ability to spot trends that are out there, not to overanalyze any single event,” explained Mr. Reinecke, principal of Reinecke Strategic Solutions, Bethesda, Md.

The labeling of dietary supplements will be required to include an address or telephone number consumers can use to contact the manufacturer or other responsible party, should an adverse event occur.

Any product without this informaton on the label will be considered misbranded, Mr. Reinecke said at the meeting, which was cosponsored by the University of California, San Diego.

Manufacturers, packers, and distributors will be required to maintain for 6 years all records relating to adverse event reports.

Falsification of any records will be illegal, and could lead to an injunction or criminal penalties.

The recent change of leadership in Congress is likely to result in greater efforts to ensure the safety of supplements, particularly by implementing and making final the DSHEA provision that establishes good manufacturing practices governing the preparation, packing, and holding of these products, said Mr. Reinecke, who was one of the Capitol Hill staffers involved in writing DSHEA.

“This provision is long overdue and greatly needed,” he said.

“The coming year also is likely to see the biggest effort in Washington in the 20-something years I've been there to get the FDA some much-needed resources. This will be difficult given the fiscal situation in which we find ourselves, but there is strong support for this in industry and consumer groups,” he said.

LA JOLLA, CALIF. — The newly enacted Dietary Supplement and Nonprescription Drug Consumer Protection Act mandates for the first time the reporting of serious adverse events associated with dietary supplements and over-the-counter products.

The law, passed by Congress in December, is the first revision of the regulation of dietary supplements since the passage of the Dietary Supplement Health and Education Act (DSHEA) of 1994, Peter Reinecke said at a symposium on natural supplements sponsored by the Scripps Center for Integrative Medicine.

DSHEA authorized the Food and Drug Administration (FDA) to seize products that are adulterated or misbranded and to remove from the market products that present significant or unreasonable risk of injury or illness or that pose an imminent hazard to public health or safety. It made no provision for the same type of reporting of adverse events that is required for pharmaceutical drugs.

But when the new law goes into effect on Dec. 22, 2007, all manufacturers, packers, and distributors of supplements will be required to report serious adverse events to the FDA within 15 business days through the MedWatch program.

Serious adverse events are defined as those that result in death, a life-threatening experience, inpatient hospitalization, persistent or significant disability or incapacity, or a congenital abnormality or birth defect; or that require, based on reasonable medical judgment, a medical or surgical intervention to prevent one of these outcomes.

If a consumer reports that he or she has experienced a serious adverse event, the manufacturer must report it–regardless of whether proof is provided, medical care was sought, or the company disagrees with the claim.

“The intent of the new law is clearly to err on the side of over-reporting to give the FDA the ability to spot trends that are out there, not to overanalyze any single event,” explained Mr. Reinecke, principal of Reinecke Strategic Solutions, Bethesda, Md.

The labeling of dietary supplements will be required to include an address or telephone number consumers can use to contact the manufacturer or other responsible party, should an adverse event occur.

Any product without this informaton on the label will be considered misbranded, Mr. Reinecke said at the meeting, which was cosponsored by the University of California, San Diego.

Manufacturers, packers, and distributors will be required to maintain for 6 years all records relating to adverse event reports.

Falsification of any records will be illegal, and could lead to an injunction or criminal penalties.

The recent change of leadership in Congress is likely to result in greater efforts to ensure the safety of supplements, particularly by implementing and making final the DSHEA provision that establishes good manufacturing practices governing the preparation, packing, and holding of these products, said Mr. Reinecke, who was one of the Capitol Hill staffers involved in writing DSHEA.

“This provision is long overdue and greatly needed,” he said.

“The coming year also is likely to see the biggest effort in Washington in the 20-something years I've been there to get the FDA some much-needed resources. This will be difficult given the fiscal situation in which we find ourselves, but there is strong support for this in industry and consumer groups,” he said.

The link between chronic hepatitis C infection and the onset of disordered autoimmunity continues to grow in both certainty and complexity, with new pathogenic insights emerging and with important implications for diagnosis, treatment, and prognosis.

Since identification of the hepatitis C virus (HCV) in 1989, it has become clear that the chronic infection can be accompanied by a variety of systemic autoreactive phenomena, most notably vasculitis.

This virus replicates very rapidly, turning over billions of times each day and chronically stimulating the immune system, said Dr. Leonard H. Calabrese, professor of medicine at Case Western Reserve University, Cleveland.

In approximately half of patients, this chronic immune stimulation leads to the development of autoreactivity and the appearance of rheumatoid factor (RF) in serum. Some patients also are found to have cryoglobulins, and a subset develop autoimmune conditions such as cryoglobulinemic vasculitis with symptoms of purpura, glomerulonephritis, peripheral neuropathy, and polyarthritis. B-cell lymphomas also can occur.

These patients represent a diagnostic challenge. Clinical suspicion for the virus must remain high because most patients infected with HCV remain undiagnosed and because they can present not only with hepatic abnormalities but with a wide range of vasculitis-associated symptoms, he said.

Treatment is problematic too. “The first issue is whether or not [patients] need treatment for the hepatitis, and it's necessary to bring in the resources of hepatology to make this determination,” Dr. Calabrese said in an interview.

In many patients, aggressive antiviral treatment with peginterferon and ribavirin will clear both the virus and the autoimmune symptoms. However, in some patients, symptoms of vasculitis persist despite treatment, and in at least half of patients the viral infection is not controlled or the treatment cannot be tolerated. These patients pose significant therapeutic challenges, according to Dr. Calabrese, because standard treatments for vasculitis are immunosuppressive, and these patients have a lifelong, potentially lethal infection that could worsen with the use of agents such as glucocorticoids.

Other therapeutic strategies being investigated include the use of rituximab to target the B cells that are the source of the autoantibodies, but the data with this agent are preliminary and the numbers are small, he said.

Another new approach involves targeting a factor known as B-lymphocyte stimulator (BLyS), which has been linked in recent reports with both HCV and autoimmunity.

BLyS is a protein belonging to the tumor necrosis factor superfamily that was first discovered by scientists at Human Genome Sciences, Rockville, Md., in 1999. It is secreted by monocytes, macrophages, and dendritic cells and promotes differentiation and proliferation of autoreactive B cells, and its overproduction can disrupt immune tolerance by inhibiting B-cell apoptosis. It is known to be upregulated in some patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjögren's syndrome.

One group of researchers from L'Hôpital Pitié-Salpêtrière, Paris, recently reported on 76 consecutive HCV-infected patients, 47 (62%) of whom were positive for mixed (types II and III) cryoglobulins, and 27 (36%) of whom had systemic vasculitis. Arthralgias were present in 30 (40%), purpura in 20 (26%), peripheral neuropathy in 19 (25%), and glomerulonephritis in 6 (8%).

Significant correlations were seen in BLyS levels, cryoglobulin levels, RF positivity, arthralgias, and the presence of systemic vasculitis among these HCV-positive patients. On multiple regression analysis, the presence of type II cryoglobulins was associated with high levels of BLyS, with a correlation coefficient of 0.406 (Rheumatology 2007;46:65–9).

One of the investigators, Dr. Patrice Cacoub, confirmed in an interview that his findings support the linkage of BLyS overexpression with HCV-induced autoimmunity. Of his findings he wrote, “They also create an exciting prospect for the use of anti-BLyS antibodies or decoy BLyS receptors in the future therapeutic algorithm of HCV-infected patients with severe mixed cryoglobulins-associated vasculitis.” He and his colleagues also noted that the mechanisms involved in B-cell proliferation associated with HCV infection are incompletely understood and suggested that induction of the antiapoptotic gene Bc12 may be involved.

A second group of researchers from Israel studied 65 patients with chronic HCV infection, comparing them with 57 patients with SLE and with 15 patients with chronic hepatitis B virus (HBV) infection, with 35 healthy volunteers acting as controls.

Mean serum BLyS level in patients with HCV was elevated, at 2.4 ng/mL. The mean level among patients with SLE was 3.1 ng/mL, while it was only 1.1 ng/mL in both HBV patients and healthy controls.

Serum levels of BLyS were elevated in 29% of patients with HCV and in 32% of patients with SLE but in none of the healthy patients.

Among the HCV-infected patients, elevated BLyS levels also were associated with the presence of arthralgias, anticardiolipin antibodies, and cryoglobulins. A total of 89% of those with elevated BLyS had detectable cryoglobulins, compared with 23% of those with normal levels of BLyS (J. Autoimmunity 2006;27:134–9).

Another group of researchers from northern Italy reported on 66 patients with mixed cryoglobulinemia and frank vasculitis, 54 (82%) of whom were positive for HCV. They compared this group with 33 HCV-positive patients who were either cryoglobulin negative or had detectable cryoglobulins but were asymptomatic, and with 48 healthy blood donors. They found a significantly higher frequency of BLyS positivity, both among patients with mixed cryoglobulinemia and among those who were HCV positive without evidence of cryoglobulins.

These investigators also noted that their finding of a subgroup of patients with mixed cryoglobulinemia without HCV infection suggests that other infectious agents also may be capable of triggering the BLyS deregulation that results in the formation of cryoglobulins (Rheumatology 2007;46:37–43).

The need for investigations into other possible etiologic factors also was highlighted in a recent presentation at the International Congress on Autoimmunity in Sorrento, Italy. Dr. Jan Willem Cohen Tervaert reviewed the experience at the University Hospital Maastricht, the Netherlands, where 22 patients with cryoglobulinemia have been treated during the past 5 years—none of whom had HCV detectable either serologically or by polymerase chain reaction. In the Netherlands, the prevalence is low, at 0.098%, with infection found primarily among drug users and immigrants, he said.

In this group of patients, 86% had constitutional symptoms such as fever and malaise. Skin vasculitis and glomerulonephritis each were present in 41%, arthritis in 73%, and peripheral neuropathy in one-third. C-reactive protein was elevated in 73%, RF was present in 67%, and complement levels were low in 70%. Despite the fact that none of the patients had HCV infection, liver function abnormalities were seen in 36%, Dr. Cohen Tervaert said. Two had vasculitis associated with lymphoproliferative disease and 10 also had connective tissue diseases such as Sjögren's syndrome and SLE.

This series demonstrated that non-HCV cryoglobulinemia tends to be more severe than when the autoimmune disorder results from HCV, he said.

This observation also was made by Dr. Cacoub's group in Paris, who compared 65 patients with non-HCV cryoglobulinemia with 118 patients with HCV infection and cryoglobulinemia. The non-HCV patients had a fourfold increased risk of developing B-cell non-Hodgkins lymphoma (Arch. Intern. Med. 2006;166:2101–8).

The link between chronic hepatitis C infection and the onset of disordered autoimmunity continues to grow in both certainty and complexity, with new pathogenic insights emerging and with important implications for diagnosis, treatment, and prognosis.

Since identification of the hepatitis C virus (HCV) in 1989, it has become clear that the chronic infection can be accompanied by a variety of systemic autoreactive phenomena, most notably vasculitis.

This virus replicates very rapidly, turning over billions of times each day and chronically stimulating the immune system, said Dr. Leonard H. Calabrese, professor of medicine at Case Western Reserve University, Cleveland.

In approximately half of patients, this chronic immune stimulation leads to the development of autoreactivity and the appearance of rheumatoid factor (RF) in serum. Some patients also are found to have cryoglobulins, and a subset develop autoimmune conditions such as cryoglobulinemic vasculitis with symptoms of purpura, glomerulonephritis, peripheral neuropathy, and polyarthritis. B-cell lymphomas also can occur.

These patients represent a diagnostic challenge. Clinical suspicion for the virus must remain high because most patients infected with HCV remain undiagnosed and because they can present not only with hepatic abnormalities but with a wide range of vasculitis-associated symptoms, he said.

Treatment is problematic too. “The first issue is whether or not [patients] need treatment for the hepatitis, and it's necessary to bring in the resources of hepatology to make this determination,” Dr. Calabrese said in an interview.

In many patients, aggressive antiviral treatment with peginterferon and ribavirin will clear both the virus and the autoimmune symptoms. However, in some patients, symptoms of vasculitis persist despite treatment, and in at least half of patients the viral infection is not controlled or the treatment cannot be tolerated. These patients pose significant therapeutic challenges, according to Dr. Calabrese, because standard treatments for vasculitis are immunosuppressive, and these patients have a lifelong, potentially lethal infection that could worsen with the use of agents such as glucocorticoids.

Other therapeutic strategies being investigated include the use of rituximab to target the B cells that are the source of the autoantibodies, but the data with this agent are preliminary and the numbers are small, he said.

Another new approach involves targeting a factor known as B-lymphocyte stimulator (BLyS), which has been linked in recent reports with both HCV and autoimmunity.

BLyS is a protein belonging to the tumor necrosis factor superfamily that was first discovered by scientists at Human Genome Sciences, Rockville, Md., in 1999. It is secreted by monocytes, macrophages, and dendritic cells and promotes differentiation and proliferation of autoreactive B cells, and its overproduction can disrupt immune tolerance by inhibiting B-cell apoptosis. It is known to be upregulated in some patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjögren's syndrome.

One group of researchers from L'Hôpital Pitié-Salpêtrière, Paris, recently reported on 76 consecutive HCV-infected patients, 47 (62%) of whom were positive for mixed (types II and III) cryoglobulins, and 27 (36%) of whom had systemic vasculitis. Arthralgias were present in 30 (40%), purpura in 20 (26%), peripheral neuropathy in 19 (25%), and glomerulonephritis in 6 (8%).

Significant correlations were seen in BLyS levels, cryoglobulin levels, RF positivity, arthralgias, and the presence of systemic vasculitis among these HCV-positive patients. On multiple regression analysis, the presence of type II cryoglobulins was associated with high levels of BLyS, with a correlation coefficient of 0.406 (Rheumatology 2007;46:65–9).

One of the investigators, Dr. Patrice Cacoub, confirmed in an interview that his findings support the linkage of BLyS overexpression with HCV-induced autoimmunity. Of his findings he wrote, “They also create an exciting prospect for the use of anti-BLyS antibodies or decoy BLyS receptors in the future therapeutic algorithm of HCV-infected patients with severe mixed cryoglobulins-associated vasculitis.” He and his colleagues also noted that the mechanisms involved in B-cell proliferation associated with HCV infection are incompletely understood and suggested that induction of the antiapoptotic gene Bc12 may be involved.

A second group of researchers from Israel studied 65 patients with chronic HCV infection, comparing them with 57 patients with SLE and with 15 patients with chronic hepatitis B virus (HBV) infection, with 35 healthy volunteers acting as controls.

Mean serum BLyS level in patients with HCV was elevated, at 2.4 ng/mL. The mean level among patients with SLE was 3.1 ng/mL, while it was only 1.1 ng/mL in both HBV patients and healthy controls.

Serum levels of BLyS were elevated in 29% of patients with HCV and in 32% of patients with SLE but in none of the healthy patients.

Among the HCV-infected patients, elevated BLyS levels also were associated with the presence of arthralgias, anticardiolipin antibodies, and cryoglobulins. A total of 89% of those with elevated BLyS had detectable cryoglobulins, compared with 23% of those with normal levels of BLyS (J. Autoimmunity 2006;27:134–9).

Another group of researchers from northern Italy reported on 66 patients with mixed cryoglobulinemia and frank vasculitis, 54 (82%) of whom were positive for HCV. They compared this group with 33 HCV-positive patients who were either cryoglobulin negative or had detectable cryoglobulins but were asymptomatic, and with 48 healthy blood donors. They found a significantly higher frequency of BLyS positivity, both among patients with mixed cryoglobulinemia and among those who were HCV positive without evidence of cryoglobulins.

These investigators also noted that their finding of a subgroup of patients with mixed cryoglobulinemia without HCV infection suggests that other infectious agents also may be capable of triggering the BLyS deregulation that results in the formation of cryoglobulins (Rheumatology 2007;46:37–43).

The need for investigations into other possible etiologic factors also was highlighted in a recent presentation at the International Congress on Autoimmunity in Sorrento, Italy. Dr. Jan Willem Cohen Tervaert reviewed the experience at the University Hospital Maastricht, the Netherlands, where 22 patients with cryoglobulinemia have been treated during the past 5 years—none of whom had HCV detectable either serologically or by polymerase chain reaction. In the Netherlands, the prevalence is low, at 0.098%, with infection found primarily among drug users and immigrants, he said.

In this group of patients, 86% had constitutional symptoms such as fever and malaise. Skin vasculitis and glomerulonephritis each were present in 41%, arthritis in 73%, and peripheral neuropathy in one-third. C-reactive protein was elevated in 73%, RF was present in 67%, and complement levels were low in 70%. Despite the fact that none of the patients had HCV infection, liver function abnormalities were seen in 36%, Dr. Cohen Tervaert said. Two had vasculitis associated with lymphoproliferative disease and 10 also had connective tissue diseases such as Sjögren's syndrome and SLE.

This series demonstrated that non-HCV cryoglobulinemia tends to be more severe than when the autoimmune disorder results from HCV, he said.

This observation also was made by Dr. Cacoub's group in Paris, who compared 65 patients with non-HCV cryoglobulinemia with 118 patients with HCV infection and cryoglobulinemia. The non-HCV patients had a fourfold increased risk of developing B-cell non-Hodgkins lymphoma (Arch. Intern. Med. 2006;166:2101–8).

The link between chronic hepatitis C infection and the onset of disordered autoimmunity continues to grow in both certainty and complexity, with new pathogenic insights emerging and with important implications for diagnosis, treatment, and prognosis.

Since identification of the hepatitis C virus (HCV) in 1989, it has become clear that the chronic infection can be accompanied by a variety of systemic autoreactive phenomena, most notably vasculitis.

This virus replicates very rapidly, turning over billions of times each day and chronically stimulating the immune system, said Dr. Leonard H. Calabrese, professor of medicine at Case Western Reserve University, Cleveland.

In approximately half of patients, this chronic immune stimulation leads to the development of autoreactivity and the appearance of rheumatoid factor (RF) in serum. Some patients also are found to have cryoglobulins, and a subset develop autoimmune conditions such as cryoglobulinemic vasculitis with symptoms of purpura, glomerulonephritis, peripheral neuropathy, and polyarthritis. B-cell lymphomas also can occur.

These patients represent a diagnostic challenge. Clinical suspicion for the virus must remain high because most patients infected with HCV remain undiagnosed and because they can present not only with hepatic abnormalities but with a wide range of vasculitis-associated symptoms, he said.

Treatment is problematic too. “The first issue is whether or not [patients] need treatment for the hepatitis, and it's necessary to bring in the resources of hepatology to make this determination,” Dr. Calabrese said in an interview.

In many patients, aggressive antiviral treatment with peginterferon and ribavirin will clear both the virus and the autoimmune symptoms. However, in some patients, symptoms of vasculitis persist despite treatment, and in at least half of patients the viral infection is not controlled or the treatment cannot be tolerated. These patients pose significant therapeutic challenges, according to Dr. Calabrese, because standard treatments for vasculitis are immunosuppressive, and these patients have a lifelong, potentially lethal infection that could worsen with the use of agents such as glucocorticoids.

Other therapeutic strategies being investigated include the use of rituximab to target the B cells that are the source of the autoantibodies, but the data with this agent are preliminary and the numbers are small, he said.

Another new approach involves targeting a factor known as B-lymphocyte stimulator (BLyS), which has been linked in recent reports with both HCV and autoimmunity.

BLyS is a protein belonging to the tumor necrosis factor superfamily that was first discovered by scientists at Human Genome Sciences, Rockville, Md., in 1999. It is secreted by monocytes, macrophages, and dendritic cells and promotes differentiation and proliferation of autoreactive B cells, and its overproduction can disrupt immune tolerance by inhibiting B-cell apoptosis. It is known to be upregulated in some patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjögren's syndrome.

One group of researchers from L'Hôpital Pitié-Salpêtrière, Paris, recently reported on 76 consecutive HCV-infected patients, 47 (62%) of whom were positive for mixed (types II and III) cryoglobulins, and 27 (36%) of whom had systemic vasculitis. Arthralgias were present in 30 (40%), purpura in 20 (26%), peripheral neuropathy in 19 (25%), and glomerulonephritis in 6 (8%).

Significant correlations were seen in BLyS levels, cryoglobulin levels, RF positivity, arthralgias, and the presence of systemic vasculitis among these HCV-positive patients. On multiple regression analysis, the presence of type II cryoglobulins was associated with high levels of BLyS, with a correlation coefficient of 0.406 (Rheumatology 2007;46:65–9).

One of the investigators, Dr. Patrice Cacoub, confirmed in an interview that his findings support the linkage of BLyS overexpression with HCV-induced autoimmunity. Of his findings he wrote, “They also create an exciting prospect for the use of anti-BLyS antibodies or decoy BLyS receptors in the future therapeutic algorithm of HCV-infected patients with severe mixed cryoglobulins-associated vasculitis.” He and his colleagues also noted that the mechanisms involved in B-cell proliferation associated with HCV infection are incompletely understood and suggested that induction of the antiapoptotic gene Bc12 may be involved.

A second group of researchers from Israel studied 65 patients with chronic HCV infection, comparing them with 57 patients with SLE and with 15 patients with chronic hepatitis B virus (HBV) infection, with 35 healthy volunteers acting as controls.

Mean serum BLyS level in patients with HCV was elevated, at 2.4 ng/mL. The mean level among patients with SLE was 3.1 ng/mL, while it was only 1.1 ng/mL in both HBV patients and healthy controls.

Serum levels of BLyS were elevated in 29% of patients with HCV and in 32% of patients with SLE but in none of the healthy patients.

Among the HCV-infected patients, elevated BLyS levels also were associated with the presence of arthralgias, anticardiolipin antibodies, and cryoglobulins. A total of 89% of those with elevated BLyS had detectable cryoglobulins, compared with 23% of those with normal levels of BLyS (J. Autoimmunity 2006;27:134–9).

Another group of researchers from northern Italy reported on 66 patients with mixed cryoglobulinemia and frank vasculitis, 54 (82%) of whom were positive for HCV. They compared this group with 33 HCV-positive patients who were either cryoglobulin negative or had detectable cryoglobulins but were asymptomatic, and with 48 healthy blood donors. They found a significantly higher frequency of BLyS positivity, both among patients with mixed cryoglobulinemia and among those who were HCV positive without evidence of cryoglobulins.

These investigators also noted that their finding of a subgroup of patients with mixed cryoglobulinemia without HCV infection suggests that other infectious agents also may be capable of triggering the BLyS deregulation that results in the formation of cryoglobulins (Rheumatology 2007;46:37–43).

The need for investigations into other possible etiologic factors also was highlighted in a recent presentation at the International Congress on Autoimmunity in Sorrento, Italy. Dr. Jan Willem Cohen Tervaert reviewed the experience at the University Hospital Maastricht, the Netherlands, where 22 patients with cryoglobulinemia have been treated during the past 5 years—none of whom had HCV detectable either serologically or by polymerase chain reaction. In the Netherlands, the prevalence is low, at 0.098%, with infection found primarily among drug users and immigrants, he said.

In this group of patients, 86% had constitutional symptoms such as fever and malaise. Skin vasculitis and glomerulonephritis each were present in 41%, arthritis in 73%, and peripheral neuropathy in one-third. C-reactive protein was elevated in 73%, RF was present in 67%, and complement levels were low in 70%. Despite the fact that none of the patients had HCV infection, liver function abnormalities were seen in 36%, Dr. Cohen Tervaert said. Two had vasculitis associated with lymphoproliferative disease and 10 also had connective tissue diseases such as Sjögren's syndrome and SLE.

This series demonstrated that non-HCV cryoglobulinemia tends to be more severe than when the autoimmune disorder results from HCV, he said.

This observation also was made by Dr. Cacoub's group in Paris, who compared 65 patients with non-HCV cryoglobulinemia with 118 patients with HCV infection and cryoglobulinemia. The non-HCV patients had a fourfold increased risk of developing B-cell non-Hodgkins lymphoma (Arch. Intern. Med. 2006;166:2101–8).

BOSTON — The first boarding school for obese adolescents is having unprecedented success in helping overweight teens lose significant quantities of weight, increase their level of fitness, and reap emotional rewards of improved self-esteem, academic performance, and mood.

The 15 members of the first class at the Academy of the Sierras (AOS) lost an average of 85 pounds during their two semesters at the Reedley, Calif., school and have maintained the weight loss for 10 months of follow-up, according to Daniel S. Kirschenbaum, Ph.D., clinical director of the academy.

The class comprised eight boys and seven girls who were about 15 years old. On admission, they averaged 100% overweight, with the least overweight student being 60% overweight. Their mean body mass index (BMI) was 43.1 kg/m

At 10 months' follow-up, 60% were no more than 30% overweight, and 87% were below 60% overweight. The mean BMI had decreased to 30.6 kg/m

In addition to weight loss, participants also exhibited significant improvements in fitness, emotional functioning, and academic performance, Dr. Kirschenbaum reported at the annual meeting of NAASO, the Obesity Society. Research findings have suggested that overweight teens are not only at risk for multiple future health problems, but also experience numerous difficulties with self-esteem, depression, and isolation, he said. Failure in school and problem behaviors often result.

The AOS approach interrupts this cycle by means of a scientifically based immersion program that includes intensive cognitive-behavioral therapy, a very-low-fat diet, and an integrated academic program.

One basic premise that is stressed is that being overweight is a biologic challenge that must be faced in a proactive fashion. “We emphasize that their biology is dead set against long-term weight loss, but that biology isn't destiny,” Dr. Kirschenbaum said in an interview. “We encourage them to think of themselves as athletes who are trying to transform their bodies, acknowledging the very real difficulty of the task.”

These concepts are central to the cognitive behavioral component of the program, with the intention of helping obese adolescents face their commitment from a position of greater strength. “In the four cognitive-behavioral sessions students have each week, we really try to get them to understand that it's not just about losing weight, it's about reorienting their lives,” he said.

The result in this group of students showed significant improvements in emotional states. On all three domains of the Child Depression Inventory—total or overall mood, emotional problems, and functional problems—initial scores that approached clinically significant elevations were reduced to the normal range.

Another facet of the program is activity management. The students wear pedometers and are encouraged to take at least 10,000 steps per day, and even as many as 20,000, which approximates 10 miles of walking.

On one measure of fitness, the timed mile, the average time during the two semesters decreased from 18 minutes to 12.5 minutes. The cohort's initial average resting pulse rate, high at 85.3 beats/min, fell to a normal 69 beats/min, and upper body strength as measured by chest presses increased from 60.4 pounds to 76 pounds.

The accredited academic program not only includes a full load of core courses but also is integrated with the personal development side of the program. For example, in math classes, statistics are taught, so the students themselves can read and evaluate scientific studies on weight loss, explained Dr. Kirschenbaum, who also is a professor of psychiatry and behavioral sciences at Northwestern University, Chicago.

A further crucial focus is the carefully designed, very-low-fat diet that is “teen friendly,” including such items as low-fat pizza, vegetarian chili, and oatmeal cookies. The diet provides approximately 1,300 calories/day, with about 8 g fat and 50 g protein.

Certain foods, such as entrees and snacks, are controlled in quantity, but low-density foods such as salads and fruits can be eaten ad libitum at each meal. With these foods, the students must learn to exercise self-control, playing an active role in their weight management.

“We try to balance our external control with self-control, exerting enough external control to increase the probability of their being successful,” Dr. Kirschenbaum said.

Preparing the students for transition back to their families and social circles—as well as to the larger obesogenic environment—is emphasized. For example, during their stay at AOS, the students are taken out to restaurants on occasion and are allowed to order whatever they wish. This increases their ability to deal with the stress of exposure to potentially problematic foods. When they make poor choices, the program gives the students time to analyze and try to understand their behavior.

Follow-up after the students leave the program includes extensive family involvement and an Internet-based aftercare program. Although longer-term follow-up clearly will be needed to fully evaluate the effects of the program, current support for it is justified by the magnitude and consistency of behavioral and activity changes seen in this first AOS class, Dr. Kirschenbaum said.

Academy of the Sierras students combine academics with a special diet and activity management. The student on the left (also shown in the photo on the right) lost a total of 73 pounds in 7 months. Academy of the Sierras

BOSTON — The first boarding school for obese adolescents is having unprecedented success in helping overweight teens lose significant quantities of weight, increase their level of fitness, and reap emotional rewards of improved self-esteem, academic performance, and mood.

The 15 members of the first class at the Academy of the Sierras (AOS) lost an average of 85 pounds during their two semesters at the Reedley, Calif., school and have maintained the weight loss for 10 months of follow-up, according to Daniel S. Kirschenbaum, Ph.D., clinical director of the academy.

The class comprised eight boys and seven girls who were about 15 years old. On admission, they averaged 100% overweight, with the least overweight student being 60% overweight. Their mean body mass index (BMI) was 43.1 kg/m

At 10 months' follow-up, 60% were no more than 30% overweight, and 87% were below 60% overweight. The mean BMI had decreased to 30.6 kg/m

In addition to weight loss, participants also exhibited significant improvements in fitness, emotional functioning, and academic performance, Dr. Kirschenbaum reported at the annual meeting of NAASO, the Obesity Society. Research findings have suggested that overweight teens are not only at risk for multiple future health problems, but also experience numerous difficulties with self-esteem, depression, and isolation, he said. Failure in school and problem behaviors often result.

The AOS approach interrupts this cycle by means of a scientifically based immersion program that includes intensive cognitive-behavioral therapy, a very-low-fat diet, and an integrated academic program.

One basic premise that is stressed is that being overweight is a biologic challenge that must be faced in a proactive fashion. “We emphasize that their biology is dead set against long-term weight loss, but that biology isn't destiny,” Dr. Kirschenbaum said in an interview. “We encourage them to think of themselves as athletes who are trying to transform their bodies, acknowledging the very real difficulty of the task.”

These concepts are central to the cognitive behavioral component of the program, with the intention of helping obese adolescents face their commitment from a position of greater strength. “In the four cognitive-behavioral sessions students have each week, we really try to get them to understand that it's not just about losing weight, it's about reorienting their lives,” he said.

The result in this group of students showed significant improvements in emotional states. On all three domains of the Child Depression Inventory—total or overall mood, emotional problems, and functional problems—initial scores that approached clinically significant elevations were reduced to the normal range.

Another facet of the program is activity management. The students wear pedometers and are encouraged to take at least 10,000 steps per day, and even as many as 20,000, which approximates 10 miles of walking.

On one measure of fitness, the timed mile, the average time during the two semesters decreased from 18 minutes to 12.5 minutes. The cohort's initial average resting pulse rate, high at 85.3 beats/min, fell to a normal 69 beats/min, and upper body strength as measured by chest presses increased from 60.4 pounds to 76 pounds.

The accredited academic program not only includes a full load of core courses but also is integrated with the personal development side of the program. For example, in math classes, statistics are taught, so the students themselves can read and evaluate scientific studies on weight loss, explained Dr. Kirschenbaum, who also is a professor of psychiatry and behavioral sciences at Northwestern University, Chicago.

A further crucial focus is the carefully designed, very-low-fat diet that is “teen friendly,” including such items as low-fat pizza, vegetarian chili, and oatmeal cookies. The diet provides approximately 1,300 calories/day, with about 8 g fat and 50 g protein.

Certain foods, such as entrees and snacks, are controlled in quantity, but low-density foods such as salads and fruits can be eaten ad libitum at each meal. With these foods, the students must learn to exercise self-control, playing an active role in their weight management.

“We try to balance our external control with self-control, exerting enough external control to increase the probability of their being successful,” Dr. Kirschenbaum said.

Preparing the students for transition back to their families and social circles—as well as to the larger obesogenic environment—is emphasized. For example, during their stay at AOS, the students are taken out to restaurants on occasion and are allowed to order whatever they wish. This increases their ability to deal with the stress of exposure to potentially problematic foods. When they make poor choices, the program gives the students time to analyze and try to understand their behavior.

Follow-up after the students leave the program includes extensive family involvement and an Internet-based aftercare program. Although longer-term follow-up clearly will be needed to fully evaluate the effects of the program, current support for it is justified by the magnitude and consistency of behavioral and activity changes seen in this first AOS class, Dr. Kirschenbaum said.

Academy of the Sierras students combine academics with a special diet and activity management. The student on the left (also shown in the photo on the right) lost a total of 73 pounds in 7 months. Academy of the Sierras

BOSTON — The first boarding school for obese adolescents is having unprecedented success in helping overweight teens lose significant quantities of weight, increase their level of fitness, and reap emotional rewards of improved self-esteem, academic performance, and mood.

The 15 members of the first class at the Academy of the Sierras (AOS) lost an average of 85 pounds during their two semesters at the Reedley, Calif., school and have maintained the weight loss for 10 months of follow-up, according to Daniel S. Kirschenbaum, Ph.D., clinical director of the academy.

The class comprised eight boys and seven girls who were about 15 years old. On admission, they averaged 100% overweight, with the least overweight student being 60% overweight. Their mean body mass index (BMI) was 43.1 kg/m

At 10 months' follow-up, 60% were no more than 30% overweight, and 87% were below 60% overweight. The mean BMI had decreased to 30.6 kg/m

In addition to weight loss, participants also exhibited significant improvements in fitness, emotional functioning, and academic performance, Dr. Kirschenbaum reported at the annual meeting of NAASO, the Obesity Society. Research findings have suggested that overweight teens are not only at risk for multiple future health problems, but also experience numerous difficulties with self-esteem, depression, and isolation, he said. Failure in school and problem behaviors often result.

The AOS approach interrupts this cycle by means of a scientifically based immersion program that includes intensive cognitive-behavioral therapy, a very-low-fat diet, and an integrated academic program.

One basic premise that is stressed is that being overweight is a biologic challenge that must be faced in a proactive fashion. “We emphasize that their biology is dead set against long-term weight loss, but that biology isn't destiny,” Dr. Kirschenbaum said in an interview. “We encourage them to think of themselves as athletes who are trying to transform their bodies, acknowledging the very real difficulty of the task.”

These concepts are central to the cognitive behavioral component of the program, with the intention of helping obese adolescents face their commitment from a position of greater strength. “In the four cognitive-behavioral sessions students have each week, we really try to get them to understand that it's not just about losing weight, it's about reorienting their lives,” he said.

The result in this group of students showed significant improvements in emotional states. On all three domains of the Child Depression Inventory—total or overall mood, emotional problems, and functional problems—initial scores that approached clinically significant elevations were reduced to the normal range.

Another facet of the program is activity management. The students wear pedometers and are encouraged to take at least 10,000 steps per day, and even as many as 20,000, which approximates 10 miles of walking.

On one measure of fitness, the timed mile, the average time during the two semesters decreased from 18 minutes to 12.5 minutes. The cohort's initial average resting pulse rate, high at 85.3 beats/min, fell to a normal 69 beats/min, and upper body strength as measured by chest presses increased from 60.4 pounds to 76 pounds.

The accredited academic program not only includes a full load of core courses but also is integrated with the personal development side of the program. For example, in math classes, statistics are taught, so the students themselves can read and evaluate scientific studies on weight loss, explained Dr. Kirschenbaum, who also is a professor of psychiatry and behavioral sciences at Northwestern University, Chicago.

A further crucial focus is the carefully designed, very-low-fat diet that is “teen friendly,” including such items as low-fat pizza, vegetarian chili, and oatmeal cookies. The diet provides approximately 1,300 calories/day, with about 8 g fat and 50 g protein.

Certain foods, such as entrees and snacks, are controlled in quantity, but low-density foods such as salads and fruits can be eaten ad libitum at each meal. With these foods, the students must learn to exercise self-control, playing an active role in their weight management.

“We try to balance our external control with self-control, exerting enough external control to increase the probability of their being successful,” Dr. Kirschenbaum said.

Preparing the students for transition back to their families and social circles—as well as to the larger obesogenic environment—is emphasized. For example, during their stay at AOS, the students are taken out to restaurants on occasion and are allowed to order whatever they wish. This increases their ability to deal with the stress of exposure to potentially problematic foods. When they make poor choices, the program gives the students time to analyze and try to understand their behavior.

Follow-up after the students leave the program includes extensive family involvement and an Internet-based aftercare program. Although longer-term follow-up clearly will be needed to fully evaluate the effects of the program, current support for it is justified by the magnitude and consistency of behavioral and activity changes seen in this first AOS class, Dr. Kirschenbaum said.

Academy of the Sierras students combine academics with a special diet and activity management. The student on the left (also shown in the photo on the right) lost a total of 73 pounds in 7 months. Academy of the Sierras

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

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

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg by intravenous injection every 3 months. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

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

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

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

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

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improved gastrointestinal tolerance, compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

The study was sponsored by Roche Laboratories.

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

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

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg by intravenous injection every 3 months. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

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

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

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

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

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improved gastrointestinal tolerance, compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

The study was sponsored by Roche Laboratories.

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

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

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg by intravenous injection every 3 months. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

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

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

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

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

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improved gastrointestinal tolerance, compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

The study was sponsored by Roche Laboratories.

SORRENTO, ITALY — Evolving experience with rituximab is demonstrating that this monoclonal antibody has multiple complex effects other than B-cell depletion in rheumatoid arthritis, including the alteration of macrophage function, Dr. Elias Toubi said at the Fifth International Congress on Autoimmunity.

B cells have multiple immunomodulatory functions that may be involved in autoimmunity. Aside from the production of antibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP), other B-cell functions in RA and other autoimmune diseases include the production of proinflammatory cytokines, regulation of other effector cells, and acting as antigen-presenting cells. Dr. Toubi of Bnai Zion Medical Center, Haifa, Israel and his colleagues studied 10 patients with RA who had previously been treated with methotrexate without benefit.

Baseline assessments included measurement of serum RF, anti-CCP, and total IgG. Also, blood monocyte-derived macrophages were analyzed for messenger RNA expression of the costimulatory molecule CD86, the immunoregulatory cytokine interleukin (IL)-10, and B cell-activating factor (BAFF), he said.

The 10 patients then underwent a single course of rituximab therapy, which consisted of two infusions of 1,000 mg 2 weeks apart. B cells were depleted at 2 and 4 months in all patients. The mean B-cell count at baseline was 199 cells/mm

Six patients achieved an ACR 50 response and were classified as responders. An additional two had partial responses, and two failed to respond.

At baseline, seven of the patients had been positive for RF and anti-CCP. Among responders RF titers fell or disappeared, but the anti-CCP antibody levels remained high.

Because anti-CCP antibodies are produced by B cells, their persistence in the context of overall B-cell depletion suggests that certain pathogenic memory B cells survive, possibly in secondary lymphoid tissue, according to Dr. Toubi.

Treatment with rituximab also altered the expression of BAFF and IL-10, as was shown in an analysis of the supernatant of cultured macrophages.

The increased expression of these factors reflects compensatory efforts to restore B-cell homeostasis, he explained.

In cultured macrophages, the expression of messenger RNA of CD86 also was increased following treatment, reflecting the maintenance of a protective immune response despite depletion (Ann. Rheum. Dis. 2006; doi:10.1136/ard.2006.062505

Furthermore, and most important, a significant reduction in tumor necrosis factor (TNF)-α following treatment also was seen in macrophages, Dr. Toubi said.

Immature macrophages are dominant in RA and are the primary producers of proinflammatory TNF-α, and a decrease in this cytokine following treatment with rituximab suggests that the immature macrophages are being replaced following depletion by more mature, less inflammatory macrophages, he said.

SORRENTO, ITALY — Evolving experience with rituximab is demonstrating that this monoclonal antibody has multiple complex effects other than B-cell depletion in rheumatoid arthritis, including the alteration of macrophage function, Dr. Elias Toubi said at the Fifth International Congress on Autoimmunity.

B cells have multiple immunomodulatory functions that may be involved in autoimmunity. Aside from the production of antibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP), other B-cell functions in RA and other autoimmune diseases include the production of proinflammatory cytokines, regulation of other effector cells, and acting as antigen-presenting cells. Dr. Toubi of Bnai Zion Medical Center, Haifa, Israel and his colleagues studied 10 patients with RA who had previously been treated with methotrexate without benefit.

Baseline assessments included measurement of serum RF, anti-CCP, and total IgG. Also, blood monocyte-derived macrophages were analyzed for messenger RNA expression of the costimulatory molecule CD86, the immunoregulatory cytokine interleukin (IL)-10, and B cell-activating factor (BAFF), he said.

The 10 patients then underwent a single course of rituximab therapy, which consisted of two infusions of 1,000 mg 2 weeks apart. B cells were depleted at 2 and 4 months in all patients. The mean B-cell count at baseline was 199 cells/mm

Six patients achieved an ACR 50 response and were classified as responders. An additional two had partial responses, and two failed to respond.

At baseline, seven of the patients had been positive for RF and anti-CCP. Among responders RF titers fell or disappeared, but the anti-CCP antibody levels remained high.

Because anti-CCP antibodies are produced by B cells, their persistence in the context of overall B-cell depletion suggests that certain pathogenic memory B cells survive, possibly in secondary lymphoid tissue, according to Dr. Toubi.

Treatment with rituximab also altered the expression of BAFF and IL-10, as was shown in an analysis of the supernatant of cultured macrophages.

The increased expression of these factors reflects compensatory efforts to restore B-cell homeostasis, he explained.

In cultured macrophages, the expression of messenger RNA of CD86 also was increased following treatment, reflecting the maintenance of a protective immune response despite depletion (Ann. Rheum. Dis. 2006; doi:10.1136/ard.2006.062505

Furthermore, and most important, a significant reduction in tumor necrosis factor (TNF)-α following treatment also was seen in macrophages, Dr. Toubi said.

Immature macrophages are dominant in RA and are the primary producers of proinflammatory TNF-α, and a decrease in this cytokine following treatment with rituximab suggests that the immature macrophages are being replaced following depletion by more mature, less inflammatory macrophages, he said.

SORRENTO, ITALY — Evolving experience with rituximab is demonstrating that this monoclonal antibody has multiple complex effects other than B-cell depletion in rheumatoid arthritis, including the alteration of macrophage function, Dr. Elias Toubi said at the Fifth International Congress on Autoimmunity.

B cells have multiple immunomodulatory functions that may be involved in autoimmunity. Aside from the production of antibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP), other B-cell functions in RA and other autoimmune diseases include the production of proinflammatory cytokines, regulation of other effector cells, and acting as antigen-presenting cells. Dr. Toubi of Bnai Zion Medical Center, Haifa, Israel and his colleagues studied 10 patients with RA who had previously been treated with methotrexate without benefit.

Baseline assessments included measurement of serum RF, anti-CCP, and total IgG. Also, blood monocyte-derived macrophages were analyzed for messenger RNA expression of the costimulatory molecule CD86, the immunoregulatory cytokine interleukin (IL)-10, and B cell-activating factor (BAFF), he said.

The 10 patients then underwent a single course of rituximab therapy, which consisted of two infusions of 1,000 mg 2 weeks apart. B cells were depleted at 2 and 4 months in all patients. The mean B-cell count at baseline was 199 cells/mm

Six patients achieved an ACR 50 response and were classified as responders. An additional two had partial responses, and two failed to respond.

At baseline, seven of the patients had been positive for RF and anti-CCP. Among responders RF titers fell or disappeared, but the anti-CCP antibody levels remained high.

Because anti-CCP antibodies are produced by B cells, their persistence in the context of overall B-cell depletion suggests that certain pathogenic memory B cells survive, possibly in secondary lymphoid tissue, according to Dr. Toubi.

Treatment with rituximab also altered the expression of BAFF and IL-10, as was shown in an analysis of the supernatant of cultured macrophages.

The increased expression of these factors reflects compensatory efforts to restore B-cell homeostasis, he explained.

In cultured macrophages, the expression of messenger RNA of CD86 also was increased following treatment, reflecting the maintenance of a protective immune response despite depletion (Ann. Rheum. Dis. 2006; doi:10.1136/ard.2006.062505

Furthermore, and most important, a significant reduction in tumor necrosis factor (TNF)-α following treatment also was seen in macrophages, Dr. Toubi said.

Immature macrophages are dominant in RA and are the primary producers of proinflammatory TNF-α, and a decrease in this cytokine following treatment with rituximab suggests that the immature macrophages are being replaced following depletion by more mature, less inflammatory macrophages, he said.