Sharon Worcester

Uterine compression sutures for postpartum hemorrhage are more likely to fail when there is a delay of 2-6 hours between delivery and placement of the sutures, according to a large prospective population-based study.

Of 1.2 million women who delivered in the United Kingdom between September 2007 and March 2009, 210 who were treated with a uterine compression suture to control postpartum hemorrhage had adequate information for analysis. Of those, 25% continued to bleed and underwent hysterectomy, Dr. Gilles Kayem of the University of Oxford (England) and his colleagues reported in the January issue of Obstetrics & Gynecology.

Suture failure occurred in 42% of those with a 2- to 6-hour delay in suture placement, compared with only 16% of those with earlier suture placement. After adjustment for numerous socioeconomic, maternal, and medical factors, a 2- to 6-hour delay in suture placement was found to be independently associated with a fourfold increase in the odds of hysterectomy, the investigators found (Obstet. Gynecol. 2011;117:14-20).

"One possible explanation may be that unrecognized bleeding that prolongs the delay between the delivery and the treatment increases the risk of hysterectomy," they wrote, explaining that "a higher blood loss and disseminated intravascular coagulation would lead to clinical conditions that render hysterectomy almost inevitable."

Failure in this study was also more likely in women older than age 35 years, compared with younger women (adjusted odds ratio, 2.77); those who were multiparous, compared with nulliparous women (AOR, 2.83); those who were unemployed or employed in routine or manual occupations, compared with those in managerial positions (AOR, 3.54); and those who had a vaginal delivery, compared with those who had a cesarean delivery (AOR, 6.08), the researchers found.

It is interesting, they noted, that vaginal delivery was the factor associated with the highest odds of hysterectomy in this study.

"It is possible that the obstetrician is more reluctant to perform a laparotomy to insert a compression suture after excessive bleeding after a vaginal delivery than after a cesarean delivery and that, therefore, only the women with the most severe hemorrhage were selected by the obstetrician to have a uterine compression suture after a vaginal delivery," they speculated.

Another possible explanation is that other methods – such as intrauterine balloon or uterine packing – were used successfully in some cases of hemorrhage after vaginal delivery, and thus were not identified in this study, suggesting that cases involving uterine compression sutures after a vaginal delivery may be the most serious, and no other treatment modalities were available to treat the affected patients, they noted.

No differences in failure rates were seen among suture types (B-Lynch, modified B-Lynch, and 32 other techniques such as figure-of-eight, multiple compression, or square sutures). However, because this was not a randomized study, comparisons among the suture methods were limited, as the baseline populations treated may have differed.

In all, 129 women (61%) had a hemorrhage resulting from atony. Hysterectomy rates according to the different types of uterine compression suture also were not significantly different. The hysterectomy rate was 26% in cases with atony and 23% in cases with other causes, such as placenta accreta, placenta previa, and uterine tear. After adjustment for a number of variables, the risk of hysterectomy was no different in women with atony compared with other causes of hemorrhage.

Patients included in the study were women identified via the U.K. Obstetric Surveillance System (UKOSS). Case patients were those giving birth who were treated with a uterine compression suture to treat postpartum hemorrhage.

Strengths of the study include the collection of comprehensive population-based national information about women who were treated with compression sutures for postpartum hemorrhage, the investigators said.

The findings emphasize the need for careful evaluation of blood loss following delivery so that delays in recognizing and managing hemorrhage can be avoided, they concluded.

This study was funded by the charity Wellbeing of Women. Dr. Kayem disclosed that he is the beneficiary of a postdoctoral grant from the AXA Research Fund. Another one of the study authors, Marian Knight, is funded by a personal fellowship from the National Coordinating Centre for Research Capacity Development of the National Institute for Health Research. This was an independent study from UKOSS, which is partially funded by the Policy Research Programme in the Department of Health. 

Uterine compression sutures for postpartum hemorrhage are more likely to fail when there is a delay of 2-6 hours between delivery and placement of the sutures, according to a large prospective population-based study.

Of 1.2 million women who delivered in the United Kingdom between September 2007 and March 2009, 210 who were treated with a uterine compression suture to control postpartum hemorrhage had adequate information for analysis. Of those, 25% continued to bleed and underwent hysterectomy, Dr. Gilles Kayem of the University of Oxford (England) and his colleagues reported in the January issue of Obstetrics & Gynecology.

Suture failure occurred in 42% of those with a 2- to 6-hour delay in suture placement, compared with only 16% of those with earlier suture placement. After adjustment for numerous socioeconomic, maternal, and medical factors, a 2- to 6-hour delay in suture placement was found to be independently associated with a fourfold increase in the odds of hysterectomy, the investigators found (Obstet. Gynecol. 2011;117:14-20).

"One possible explanation may be that unrecognized bleeding that prolongs the delay between the delivery and the treatment increases the risk of hysterectomy," they wrote, explaining that "a higher blood loss and disseminated intravascular coagulation would lead to clinical conditions that render hysterectomy almost inevitable."

Failure in this study was also more likely in women older than age 35 years, compared with younger women (adjusted odds ratio, 2.77); those who were multiparous, compared with nulliparous women (AOR, 2.83); those who were unemployed or employed in routine or manual occupations, compared with those in managerial positions (AOR, 3.54); and those who had a vaginal delivery, compared with those who had a cesarean delivery (AOR, 6.08), the researchers found.

It is interesting, they noted, that vaginal delivery was the factor associated with the highest odds of hysterectomy in this study.

"It is possible that the obstetrician is more reluctant to perform a laparotomy to insert a compression suture after excessive bleeding after a vaginal delivery than after a cesarean delivery and that, therefore, only the women with the most severe hemorrhage were selected by the obstetrician to have a uterine compression suture after a vaginal delivery," they speculated.

Another possible explanation is that other methods – such as intrauterine balloon or uterine packing – were used successfully in some cases of hemorrhage after vaginal delivery, and thus were not identified in this study, suggesting that cases involving uterine compression sutures after a vaginal delivery may be the most serious, and no other treatment modalities were available to treat the affected patients, they noted.

No differences in failure rates were seen among suture types (B-Lynch, modified B-Lynch, and 32 other techniques such as figure-of-eight, multiple compression, or square sutures). However, because this was not a randomized study, comparisons among the suture methods were limited, as the baseline populations treated may have differed.

In all, 129 women (61%) had a hemorrhage resulting from atony. Hysterectomy rates according to the different types of uterine compression suture also were not significantly different. The hysterectomy rate was 26% in cases with atony and 23% in cases with other causes, such as placenta accreta, placenta previa, and uterine tear. After adjustment for a number of variables, the risk of hysterectomy was no different in women with atony compared with other causes of hemorrhage.

Patients included in the study were women identified via the U.K. Obstetric Surveillance System (UKOSS). Case patients were those giving birth who were treated with a uterine compression suture to treat postpartum hemorrhage.

Strengths of the study include the collection of comprehensive population-based national information about women who were treated with compression sutures for postpartum hemorrhage, the investigators said.

The findings emphasize the need for careful evaluation of blood loss following delivery so that delays in recognizing and managing hemorrhage can be avoided, they concluded.

This study was funded by the charity Wellbeing of Women. Dr. Kayem disclosed that he is the beneficiary of a postdoctoral grant from the AXA Research Fund. Another one of the study authors, Marian Knight, is funded by a personal fellowship from the National Coordinating Centre for Research Capacity Development of the National Institute for Health Research. This was an independent study from UKOSS, which is partially funded by the Policy Research Programme in the Department of Health. 

Uterine compression sutures for postpartum hemorrhage are more likely to fail when there is a delay of 2-6 hours between delivery and placement of the sutures, according to a large prospective population-based study.

Of 1.2 million women who delivered in the United Kingdom between September 2007 and March 2009, 210 who were treated with a uterine compression suture to control postpartum hemorrhage had adequate information for analysis. Of those, 25% continued to bleed and underwent hysterectomy, Dr. Gilles Kayem of the University of Oxford (England) and his colleagues reported in the January issue of Obstetrics & Gynecology.

Suture failure occurred in 42% of those with a 2- to 6-hour delay in suture placement, compared with only 16% of those with earlier suture placement. After adjustment for numerous socioeconomic, maternal, and medical factors, a 2- to 6-hour delay in suture placement was found to be independently associated with a fourfold increase in the odds of hysterectomy, the investigators found (Obstet. Gynecol. 2011;117:14-20).

"One possible explanation may be that unrecognized bleeding that prolongs the delay between the delivery and the treatment increases the risk of hysterectomy," they wrote, explaining that "a higher blood loss and disseminated intravascular coagulation would lead to clinical conditions that render hysterectomy almost inevitable."

Failure in this study was also more likely in women older than age 35 years, compared with younger women (adjusted odds ratio, 2.77); those who were multiparous, compared with nulliparous women (AOR, 2.83); those who were unemployed or employed in routine or manual occupations, compared with those in managerial positions (AOR, 3.54); and those who had a vaginal delivery, compared with those who had a cesarean delivery (AOR, 6.08), the researchers found.

It is interesting, they noted, that vaginal delivery was the factor associated with the highest odds of hysterectomy in this study.

"It is possible that the obstetrician is more reluctant to perform a laparotomy to insert a compression suture after excessive bleeding after a vaginal delivery than after a cesarean delivery and that, therefore, only the women with the most severe hemorrhage were selected by the obstetrician to have a uterine compression suture after a vaginal delivery," they speculated.

Another possible explanation is that other methods – such as intrauterine balloon or uterine packing – were used successfully in some cases of hemorrhage after vaginal delivery, and thus were not identified in this study, suggesting that cases involving uterine compression sutures after a vaginal delivery may be the most serious, and no other treatment modalities were available to treat the affected patients, they noted.

No differences in failure rates were seen among suture types (B-Lynch, modified B-Lynch, and 32 other techniques such as figure-of-eight, multiple compression, or square sutures). However, because this was not a randomized study, comparisons among the suture methods were limited, as the baseline populations treated may have differed.

In all, 129 women (61%) had a hemorrhage resulting from atony. Hysterectomy rates according to the different types of uterine compression suture also were not significantly different. The hysterectomy rate was 26% in cases with atony and 23% in cases with other causes, such as placenta accreta, placenta previa, and uterine tear. After adjustment for a number of variables, the risk of hysterectomy was no different in women with atony compared with other causes of hemorrhage.

Patients included in the study were women identified via the U.K. Obstetric Surveillance System (UKOSS). Case patients were those giving birth who were treated with a uterine compression suture to treat postpartum hemorrhage.

Strengths of the study include the collection of comprehensive population-based national information about women who were treated with compression sutures for postpartum hemorrhage, the investigators said.

The findings emphasize the need for careful evaluation of blood loss following delivery so that delays in recognizing and managing hemorrhage can be avoided, they concluded.

This study was funded by the charity Wellbeing of Women. Dr. Kayem disclosed that he is the beneficiary of a postdoctoral grant from the AXA Research Fund. Another one of the study authors, Marian Knight, is funded by a personal fellowship from the National Coordinating Centre for Research Capacity Development of the National Institute for Health Research. This was an independent study from UKOSS, which is partially funded by the Policy Research Programme in the Department of Health. 

Parental smoking was an independent risk factor for elevated systolic blood pressure in 4,236 preschool children who were part of a blood pressure screening project in Germany.

© pmphoto/istock.com

Current smoking was reported by 29% of fathers and 21% of mothers of the children in the study, and both parents reported smoking in 12% of cases. Children who had a parent who was a smoker were significantly more likely to have higher systolic blood pressure, even after adjusting for risk factors such as body mass index, parental hypertension, and birth weight, Dr. Giacomo D. Simonetti of the University of Heidelberg (Germany), and his colleagues reported online in Circulation.

Having a parent who was a smoker increased the likelihood of having a systolic blood pressure in the top 15% of the population by 21%, the investigators found.

Other significant correlates of systolic blood pressure were gender, height, BMI, birth weight, gestational hypertension, and parental hypertension. Correlates of diastolic blood pressure were gender, height, BMI, birth weight, and parental hypertension, the investigators said (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

"Moreover, systolic and diastolic blood pressure progressively increased with the cumulative number of parent-related risk factors (parental obesity, hypertension, and smoking)," they noted.

The absolute difference in blood pressure between children with no risk factors and those with three risk factors was 3.2 mm Hg for systolic blood pressure, and 2.9 mm Hg for diastolic blood pressure, which corresponds to nearly half of a standard deviation of the blood pressure distribution in the total population, the investigators noted.

Children in the study were aged 4.0 to 7.5 years (mean 5.7 years), and were evaluated between February 2007 and October 2008. Blood pressure was measured in conjunction with a family health and lifestyle survey.

The findings demonstrate that the multifactorial dependency of blood pressure on various influences – including familial, prenatal, and environmental influences – are evident even in early childhood, they said, adding that a unique finding of this study is "the novel evidence for a BP-raising effect of environmental nicotine exposure in children as young as 4-5 years of age."

Although the effects of active and passive tobacco exposure on cardiovascular functions in adults are well known and have been widely demonstrated, the effects of passive tobacco smoke exposure on childhood blood pressure have not been reported previously.

Of note, maternal – but not paternal – cigarette consumption had a quantitative relationship with childhood blood pressure in this study, which may be a result of more at-home smoking among mothers, vs. at-work smoking among fathers. Also, the effect size of passive smoking was higher in boys than in girls, raising the question of whether the sex-preferential susceptibility of adolescent and adult males to cardiovascular risk factors also is present in younger children. This may be an interesting field of future research, the investigators suggested.

The findings of this study underscore the potential benefits of implementing strictly smoke-free environments, particularly at home. This may help preserve cardiovascular health in both adults and children, the researchers said.

The potential benefits of a smoke-free environment is supported by several lines of reasoning, including the fact that smoke-free environments have been shown to decrease cardiovascular mortality in nonsmokers, that childhood blood pressure consistently tracks into adult life, and that children whose parents smoke are more likely to become smokers themselves.

Indeed, "comprehensive interventions that seek to reduce the cardiovascular risk burden early in life by promoting lifestyle changes in all family members may prove essential for lowering the cardiovascular disease risk of future generations," the investigators concluded.

This study was funded by the Manfred-Lautenschläger Stiftung, the Reimann-Dubbers Stiftung, the Dietmar-Hopp Stiftung, and the Swiss Society of Hypertension AstraZeneca scholarship awarded to Dr. Simonetti. The investigators reported having no other disclosures.

Parental smoking was an independent risk factor for elevated systolic blood pressure in 4,236 preschool children who were part of a blood pressure screening project in Germany.

© pmphoto/istock.com

Current smoking was reported by 29% of fathers and 21% of mothers of the children in the study, and both parents reported smoking in 12% of cases. Children who had a parent who was a smoker were significantly more likely to have higher systolic blood pressure, even after adjusting for risk factors such as body mass index, parental hypertension, and birth weight, Dr. Giacomo D. Simonetti of the University of Heidelberg (Germany), and his colleagues reported online in Circulation.

Having a parent who was a smoker increased the likelihood of having a systolic blood pressure in the top 15% of the population by 21%, the investigators found.

Other significant correlates of systolic blood pressure were gender, height, BMI, birth weight, gestational hypertension, and parental hypertension. Correlates of diastolic blood pressure were gender, height, BMI, birth weight, and parental hypertension, the investigators said (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

"Moreover, systolic and diastolic blood pressure progressively increased with the cumulative number of parent-related risk factors (parental obesity, hypertension, and smoking)," they noted.

The absolute difference in blood pressure between children with no risk factors and those with three risk factors was 3.2 mm Hg for systolic blood pressure, and 2.9 mm Hg for diastolic blood pressure, which corresponds to nearly half of a standard deviation of the blood pressure distribution in the total population, the investigators noted.

Children in the study were aged 4.0 to 7.5 years (mean 5.7 years), and were evaluated between February 2007 and October 2008. Blood pressure was measured in conjunction with a family health and lifestyle survey.

The findings demonstrate that the multifactorial dependency of blood pressure on various influences – including familial, prenatal, and environmental influences – are evident even in early childhood, they said, adding that a unique finding of this study is "the novel evidence for a BP-raising effect of environmental nicotine exposure in children as young as 4-5 years of age."

Although the effects of active and passive tobacco exposure on cardiovascular functions in adults are well known and have been widely demonstrated, the effects of passive tobacco smoke exposure on childhood blood pressure have not been reported previously.

Of note, maternal – but not paternal – cigarette consumption had a quantitative relationship with childhood blood pressure in this study, which may be a result of more at-home smoking among mothers, vs. at-work smoking among fathers. Also, the effect size of passive smoking was higher in boys than in girls, raising the question of whether the sex-preferential susceptibility of adolescent and adult males to cardiovascular risk factors also is present in younger children. This may be an interesting field of future research, the investigators suggested.

The findings of this study underscore the potential benefits of implementing strictly smoke-free environments, particularly at home. This may help preserve cardiovascular health in both adults and children, the researchers said.

The potential benefits of a smoke-free environment is supported by several lines of reasoning, including the fact that smoke-free environments have been shown to decrease cardiovascular mortality in nonsmokers, that childhood blood pressure consistently tracks into adult life, and that children whose parents smoke are more likely to become smokers themselves.

Indeed, "comprehensive interventions that seek to reduce the cardiovascular risk burden early in life by promoting lifestyle changes in all family members may prove essential for lowering the cardiovascular disease risk of future generations," the investigators concluded.

This study was funded by the Manfred-Lautenschläger Stiftung, the Reimann-Dubbers Stiftung, the Dietmar-Hopp Stiftung, and the Swiss Society of Hypertension AstraZeneca scholarship awarded to Dr. Simonetti. The investigators reported having no other disclosures.

Parental smoking was an independent risk factor for elevated systolic blood pressure in 4,236 preschool children who were part of a blood pressure screening project in Germany.

© pmphoto/istock.com

Current smoking was reported by 29% of fathers and 21% of mothers of the children in the study, and both parents reported smoking in 12% of cases. Children who had a parent who was a smoker were significantly more likely to have higher systolic blood pressure, even after adjusting for risk factors such as body mass index, parental hypertension, and birth weight, Dr. Giacomo D. Simonetti of the University of Heidelberg (Germany), and his colleagues reported online in Circulation.

Having a parent who was a smoker increased the likelihood of having a systolic blood pressure in the top 15% of the population by 21%, the investigators found.

Other significant correlates of systolic blood pressure were gender, height, BMI, birth weight, gestational hypertension, and parental hypertension. Correlates of diastolic blood pressure were gender, height, BMI, birth weight, and parental hypertension, the investigators said (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

"Moreover, systolic and diastolic blood pressure progressively increased with the cumulative number of parent-related risk factors (parental obesity, hypertension, and smoking)," they noted.

The absolute difference in blood pressure between children with no risk factors and those with three risk factors was 3.2 mm Hg for systolic blood pressure, and 2.9 mm Hg for diastolic blood pressure, which corresponds to nearly half of a standard deviation of the blood pressure distribution in the total population, the investigators noted.

Children in the study were aged 4.0 to 7.5 years (mean 5.7 years), and were evaluated between February 2007 and October 2008. Blood pressure was measured in conjunction with a family health and lifestyle survey.

The findings demonstrate that the multifactorial dependency of blood pressure on various influences – including familial, prenatal, and environmental influences – are evident even in early childhood, they said, adding that a unique finding of this study is "the novel evidence for a BP-raising effect of environmental nicotine exposure in children as young as 4-5 years of age."

Although the effects of active and passive tobacco exposure on cardiovascular functions in adults are well known and have been widely demonstrated, the effects of passive tobacco smoke exposure on childhood blood pressure have not been reported previously.

Of note, maternal – but not paternal – cigarette consumption had a quantitative relationship with childhood blood pressure in this study, which may be a result of more at-home smoking among mothers, vs. at-work smoking among fathers. Also, the effect size of passive smoking was higher in boys than in girls, raising the question of whether the sex-preferential susceptibility of adolescent and adult males to cardiovascular risk factors also is present in younger children. This may be an interesting field of future research, the investigators suggested.

The findings of this study underscore the potential benefits of implementing strictly smoke-free environments, particularly at home. This may help preserve cardiovascular health in both adults and children, the researchers said.

The potential benefits of a smoke-free environment is supported by several lines of reasoning, including the fact that smoke-free environments have been shown to decrease cardiovascular mortality in nonsmokers, that childhood blood pressure consistently tracks into adult life, and that children whose parents smoke are more likely to become smokers themselves.

Indeed, "comprehensive interventions that seek to reduce the cardiovascular risk burden early in life by promoting lifestyle changes in all family members may prove essential for lowering the cardiovascular disease risk of future generations," the investigators concluded.

This study was funded by the Manfred-Lautenschläger Stiftung, the Reimann-Dubbers Stiftung, the Dietmar-Hopp Stiftung, and the Swiss Society of Hypertension AstraZeneca scholarship awarded to Dr. Simonetti. The investigators reported having no other disclosures.

Parental smoking was an independent risk factor for elevated systolic blood pressure in 4,236 preschool children who were part of a blood pressure screening project in Germany.

© pmphoto/istock.com

Current smoking was reported by 29% of fathers and 21% of mothers of the children in the study, and both parents reported smoking in 12% of cases. Children who had a parent who was a smoker were significantly more likely to have higher systolic blood pressure, even after adjusting for risk factors such as body mass index, parental hypertension, and birth weight, Dr. Giacomo D. Simonetti of the University of Heidelberg (Germany), and his colleagues reported online in Circulation.

Having a parent who was a smoker increased the likelihood of having a systolic blood pressure in the top 15% of the population by 21%, the investigators found.

Other significant correlates of systolic blood pressure were gender, height, BMI, birth weight, gestational hypertension, and parental hypertension. Correlates of diastolic blood pressure were gender, height, BMI, birth weight, and parental hypertension, the investigators said (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

"Moreover, systolic and diastolic blood pressure progressively increased with the cumulative number of parent-related risk factors (parental obesity, hypertension, and smoking)," they noted.

The absolute difference in blood pressure between children with no risk factors and those with three risk factors was 3.2 mm Hg for systolic blood pressure, and 2.9 mm Hg for diastolic blood pressure, which corresponds to nearly half of a standard deviation of the blood pressure distribution in the total population, the investigators noted.

Children in the study were aged 4.0 to 7.5 years (mean 5.7 years), and were evaluated between February 2007 and October 2008. Blood pressure was measured in conjunction with a family health and lifestyle survey.

The findings demonstrate that the multifactorial dependency of blood pressure on various influences – including familial, prenatal, and environmental influences – are evident even in early childhood, they said, adding that a unique finding of this study is "the novel evidence for a BP-raising effect of environmental nicotine exposure in children as young as 4-5 years of age."

Although the effects of active and passive tobacco exposure on cardiovascular functions in adults are well known and have been widely demonstrated, the effects of passive tobacco smoke exposure on childhood blood pressure have not been reported previously.

Of note, maternal – but not paternal – cigarette consumption had a quantitative relationship with childhood blood pressure in this study, which may be a result of more at-home smoking among mothers, vs. at-work smoking among fathers. Also, the effect size of passive smoking was higher in boys than in girls, raising the question of whether the sex-preferential susceptibility of adolescent and adult males to cardiovascular risk factors also is present in younger children. This may be an interesting field of future research, the investigators suggested.

The findings of this study underscore the potential benefits of implementing strictly smoke-free environments, particularly at home. This may help preserve cardiovascular health in both adults and children, the researchers said.

The potential benefits of a smoke-free environment is supported by several lines of reasoning, including the fact that smoke-free environments have been shown to decrease cardiovascular mortality in nonsmokers, that childhood blood pressure consistently tracks into adult life, and that children whose parents smoke are more likely to become smokers themselves.

Indeed, "comprehensive interventions that seek to reduce the cardiovascular risk burden early in life by promoting lifestyle changes in all family members may prove essential for lowering the cardiovascular disease risk of future generations," the investigators concluded.

This study was funded by the Manfred-Lautenschläger Stiftung, the Reimann-Dubbers Stiftung, the Dietmar-Hopp Stiftung, and the Swiss Society of Hypertension AstraZeneca scholarship awarded to Dr. Simonetti. The investigators reported having no other disclosures.

Parental smoking was an independent risk factor for elevated systolic blood pressure in 4,236 preschool children who were part of a blood pressure screening project in Germany.

© pmphoto/istock.com

Current smoking was reported by 29% of fathers and 21% of mothers of the children in the study, and both parents reported smoking in 12% of cases. Children who had a parent who was a smoker were significantly more likely to have higher systolic blood pressure, even after adjusting for risk factors such as body mass index, parental hypertension, and birth weight, Dr. Giacomo D. Simonetti of the University of Heidelberg (Germany), and his colleagues reported online in Circulation.

Having a parent who was a smoker increased the likelihood of having a systolic blood pressure in the top 15% of the population by 21%, the investigators found.

Other significant correlates of systolic blood pressure were gender, height, BMI, birth weight, gestational hypertension, and parental hypertension. Correlates of diastolic blood pressure were gender, height, BMI, birth weight, and parental hypertension, the investigators said (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

"Moreover, systolic and diastolic blood pressure progressively increased with the cumulative number of parent-related risk factors (parental obesity, hypertension, and smoking)," they noted.

The absolute difference in blood pressure between children with no risk factors and those with three risk factors was 3.2 mm Hg for systolic blood pressure, and 2.9 mm Hg for diastolic blood pressure, which corresponds to nearly half of a standard deviation of the blood pressure distribution in the total population, the investigators noted.

Children in the study were aged 4.0 to 7.5 years (mean 5.7 years), and were evaluated between February 2007 and October 2008. Blood pressure was measured in conjunction with a family health and lifestyle survey.

The findings demonstrate that the multifactorial dependency of blood pressure on various influences – including familial, prenatal, and environmental influences – are evident even in early childhood, they said, adding that a unique finding of this study is "the novel evidence for a BP-raising effect of environmental nicotine exposure in children as young as 4-5 years of age."

Although the effects of active and passive tobacco exposure on cardiovascular functions in adults are well known and have been widely demonstrated, the effects of passive tobacco smoke exposure on childhood blood pressure have not been reported previously.

Of note, maternal – but not paternal – cigarette consumption had a quantitative relationship with childhood blood pressure in this study, which may be a result of more at-home smoking among mothers, vs. at-work smoking among fathers. Also, the effect size of passive smoking was higher in boys than in girls, raising the question of whether the sex-preferential susceptibility of adolescent and adult males to cardiovascular risk factors also is present in younger children. This may be an interesting field of future research, the investigators suggested.

The findings of this study underscore the potential benefits of implementing strictly smoke-free environments, particularly at home. This may help preserve cardiovascular health in both adults and children, the researchers said.

The potential benefits of a smoke-free environment is supported by several lines of reasoning, including the fact that smoke-free environments have been shown to decrease cardiovascular mortality in nonsmokers, that childhood blood pressure consistently tracks into adult life, and that children whose parents smoke are more likely to become smokers themselves.

Indeed, "comprehensive interventions that seek to reduce the cardiovascular risk burden early in life by promoting lifestyle changes in all family members may prove essential for lowering the cardiovascular disease risk of future generations," the investigators concluded.

This study was funded by the Manfred-Lautenschläger Stiftung, the Reimann-Dubbers Stiftung, the Dietmar-Hopp Stiftung, and the Swiss Society of Hypertension AstraZeneca scholarship awarded to Dr. Simonetti. The investigators reported having no other disclosures.

Parental smoking was an independent risk factor for elevated systolic blood pressure in 4,236 preschool children who were part of a blood pressure screening project in Germany.

© pmphoto/istock.com

Current smoking was reported by 29% of fathers and 21% of mothers of the children in the study, and both parents reported smoking in 12% of cases. Children who had a parent who was a smoker were significantly more likely to have higher systolic blood pressure, even after adjusting for risk factors such as body mass index, parental hypertension, and birth weight, Dr. Giacomo D. Simonetti of the University of Heidelberg (Germany), and his colleagues reported online in Circulation.

Having a parent who was a smoker increased the likelihood of having a systolic blood pressure in the top 15% of the population by 21%, the investigators found.

Other significant correlates of systolic blood pressure were gender, height, BMI, birth weight, gestational hypertension, and parental hypertension. Correlates of diastolic blood pressure were gender, height, BMI, birth weight, and parental hypertension, the investigators said (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

"Moreover, systolic and diastolic blood pressure progressively increased with the cumulative number of parent-related risk factors (parental obesity, hypertension, and smoking)," they noted.

The absolute difference in blood pressure between children with no risk factors and those with three risk factors was 3.2 mm Hg for systolic blood pressure, and 2.9 mm Hg for diastolic blood pressure, which corresponds to nearly half of a standard deviation of the blood pressure distribution in the total population, the investigators noted.

Children in the study were aged 4.0 to 7.5 years (mean 5.7 years), and were evaluated between February 2007 and October 2008. Blood pressure was measured in conjunction with a family health and lifestyle survey.

The findings demonstrate that the multifactorial dependency of blood pressure on various influences – including familial, prenatal, and environmental influences – are evident even in early childhood, they said, adding that a unique finding of this study is "the novel evidence for a BP-raising effect of environmental nicotine exposure in children as young as 4-5 years of age."

Although the effects of active and passive tobacco exposure on cardiovascular functions in adults are well known and have been widely demonstrated, the effects of passive tobacco smoke exposure on childhood blood pressure have not been reported previously.

Of note, maternal – but not paternal – cigarette consumption had a quantitative relationship with childhood blood pressure in this study, which may be a result of more at-home smoking among mothers, vs. at-work smoking among fathers. Also, the effect size of passive smoking was higher in boys than in girls, raising the question of whether the sex-preferential susceptibility of adolescent and adult males to cardiovascular risk factors also is present in younger children. This may be an interesting field of future research, the investigators suggested.

The findings of this study underscore the potential benefits of implementing strictly smoke-free environments, particularly at home. This may help preserve cardiovascular health in both adults and children, the researchers said.

The potential benefits of a smoke-free environment is supported by several lines of reasoning, including the fact that smoke-free environments have been shown to decrease cardiovascular mortality in nonsmokers, that childhood blood pressure consistently tracks into adult life, and that children whose parents smoke are more likely to become smokers themselves.

Indeed, "comprehensive interventions that seek to reduce the cardiovascular risk burden early in life by promoting lifestyle changes in all family members may prove essential for lowering the cardiovascular disease risk of future generations," the investigators concluded.

This study was funded by the Manfred-Lautenschläger Stiftung, the Reimann-Dubbers Stiftung, the Dietmar-Hopp Stiftung, and the Swiss Society of Hypertension AstraZeneca scholarship awarded to Dr. Simonetti. The investigators reported having no other disclosures.

Intake of added sugars among adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased high-density lipoprotein cholesterol levels, and increased low-density lipoprotein cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

© sjlocke/istock.com

In 2,157 adolescents who participated in the survey, the daily consumption of added sugars – defined as refined calorie–containing sweeteners added to food and beverages during processing or preparation – averaged 118.9 g (28.3 tsp. or 476 calories), representing an average of 21.4% of total energy. Among those with the highest level of added sugar intake (greater than or equal to 30% of total energy or greater) and the lowest level of added sugar intake (less than 10% of total energy), respectively, the HDL cholesterol levels were 1.28 and 1.40 mmol/L, LDL cholesterol levels were 2.44 and 2.24 mmol/L, and triglycerides were 0.89 and 0.81 mmol/L, Jean A. Welsh of Emory University, Atlanta, and her colleagues reported online in the Jan. 25 issue of Circulation.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but among adolescents with at least 85th percentile of body mass index and thus considered overweight/obese, added sugar intake was positively correlated with the homeostasis model assessment (HOMA-IR), which is an estimate of insulin resistance derived from fasting glucose and insulin levels, the investigators found (Circulation 2011 Jan. 25 [doi:10.1161/CIRCULATIONAHA.110972166]).

Adjusted mean HOMA-IR (fasting insulin [pmol/L] times fasting glucose [mmol/L]/22.5) in overweight adolescents was 4.61 in those with the highest added sugar consumption, compared with 3.49 in those with the lowest consumption.

The findings contribute to a growing body of evidence linking carbohydrate and sugar intake with increased cardiovascular disease risk and are particularly important given that consumption of added sugars has increased substantially in recent decades. In 1977-1978, daily consumption of added sugars among adolescents was 62g-84 g, compared with the nearly 119 g seen in this study, representing an increase of 42%-92%, the investigators said.

Mechanisms that might explain the dysmetabolic effects of carbohydrates, and specifically sugars, include the insulin response to the metabolism of high-glycemic index foods, the increased de novo lipogenesis that results when high levels of fructose are metabolized by the liver, and the increased hepatic triglyceride synthesis combined with increased secretion and/or decreased clearance of very low-density lipoproteins, the investigators wrote.

"Modification of the effect of added sugars on measures of glucose metabolism by weight status could be explained by the decreased insulin sensitivity known to result from increased adiposity," they added.

Adolescents in this study were U.S. residents aged 12-18 years who were randomly selected to provide a fasting blood sample for NHANES 1999-2004 and who provided dietary intake information. Those with unreliable or implausible dietary data were excluded, as were those who were pregnant, those who had extreme triglyceride levels, those with previously diagnosed diabetes mellitus, and those with missing covariate data. Dietary information was merged with U.S. Department of Agriculture MyPyramid equivalents databases to determine added sugar content.

The findings support the need for dietary guidelines that call for a lower intake of added sugars, and they highlight the need for additional study as well as "comprehensive examination" of the existing evidence on the effects of added sugars on cardiovascular and other chronic disease risks, the investigators said.

The findings also suggest that minimizing added sugar consumption in adolescents might reduce their future cardiovascular disease risk, they noted.

Dr. Miriam Vos, an author on the study, disclosed receiving financial support in the form of a career award from the National Institutes of Diabetes and Digestive and Kidney Diseases and also receiving support from the Children’s Digestive Health and Nutrition Foundation. Dr. Vos also is the author of "The No-Diet Obesity Solution for Kids," (Bethesda, Md.: AGA Institute Press, 2009) for which she receives royalties. The remaining authors report no relevant financial conflicts of interest.

Intake of added sugars among adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased high-density lipoprotein cholesterol levels, and increased low-density lipoprotein cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

© sjlocke/istock.com

In 2,157 adolescents who participated in the survey, the daily consumption of added sugars – defined as refined calorie–containing sweeteners added to food and beverages during processing or preparation – averaged 118.9 g (28.3 tsp. or 476 calories), representing an average of 21.4% of total energy. Among those with the highest level of added sugar intake (greater than or equal to 30% of total energy or greater) and the lowest level of added sugar intake (less than 10% of total energy), respectively, the HDL cholesterol levels were 1.28 and 1.40 mmol/L, LDL cholesterol levels were 2.44 and 2.24 mmol/L, and triglycerides were 0.89 and 0.81 mmol/L, Jean A. Welsh of Emory University, Atlanta, and her colleagues reported online in the Jan. 25 issue of Circulation.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but among adolescents with at least 85th percentile of body mass index and thus considered overweight/obese, added sugar intake was positively correlated with the homeostasis model assessment (HOMA-IR), which is an estimate of insulin resistance derived from fasting glucose and insulin levels, the investigators found (Circulation 2011 Jan. 25 [doi:10.1161/CIRCULATIONAHA.110972166]).

Adjusted mean HOMA-IR (fasting insulin [pmol/L] times fasting glucose [mmol/L]/22.5) in overweight adolescents was 4.61 in those with the highest added sugar consumption, compared with 3.49 in those with the lowest consumption.

The findings contribute to a growing body of evidence linking carbohydrate and sugar intake with increased cardiovascular disease risk and are particularly important given that consumption of added sugars has increased substantially in recent decades. In 1977-1978, daily consumption of added sugars among adolescents was 62g-84 g, compared with the nearly 119 g seen in this study, representing an increase of 42%-92%, the investigators said.

Mechanisms that might explain the dysmetabolic effects of carbohydrates, and specifically sugars, include the insulin response to the metabolism of high-glycemic index foods, the increased de novo lipogenesis that results when high levels of fructose are metabolized by the liver, and the increased hepatic triglyceride synthesis combined with increased secretion and/or decreased clearance of very low-density lipoproteins, the investigators wrote.

"Modification of the effect of added sugars on measures of glucose metabolism by weight status could be explained by the decreased insulin sensitivity known to result from increased adiposity," they added.

Adolescents in this study were U.S. residents aged 12-18 years who were randomly selected to provide a fasting blood sample for NHANES 1999-2004 and who provided dietary intake information. Those with unreliable or implausible dietary data were excluded, as were those who were pregnant, those who had extreme triglyceride levels, those with previously diagnosed diabetes mellitus, and those with missing covariate data. Dietary information was merged with U.S. Department of Agriculture MyPyramid equivalents databases to determine added sugar content.

The findings support the need for dietary guidelines that call for a lower intake of added sugars, and they highlight the need for additional study as well as "comprehensive examination" of the existing evidence on the effects of added sugars on cardiovascular and other chronic disease risks, the investigators said.

The findings also suggest that minimizing added sugar consumption in adolescents might reduce their future cardiovascular disease risk, they noted.

Dr. Miriam Vos, an author on the study, disclosed receiving financial support in the form of a career award from the National Institutes of Diabetes and Digestive and Kidney Diseases and also receiving support from the Children’s Digestive Health and Nutrition Foundation. Dr. Vos also is the author of "The No-Diet Obesity Solution for Kids," (Bethesda, Md.: AGA Institute Press, 2009) for which she receives royalties. The remaining authors report no relevant financial conflicts of interest.

Intake of added sugars among adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased high-density lipoprotein cholesterol levels, and increased low-density lipoprotein cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

© sjlocke/istock.com

In 2,157 adolescents who participated in the survey, the daily consumption of added sugars – defined as refined calorie–containing sweeteners added to food and beverages during processing or preparation – averaged 118.9 g (28.3 tsp. or 476 calories), representing an average of 21.4% of total energy. Among those with the highest level of added sugar intake (greater than or equal to 30% of total energy or greater) and the lowest level of added sugar intake (less than 10% of total energy), respectively, the HDL cholesterol levels were 1.28 and 1.40 mmol/L, LDL cholesterol levels were 2.44 and 2.24 mmol/L, and triglycerides were 0.89 and 0.81 mmol/L, Jean A. Welsh of Emory University, Atlanta, and her colleagues reported online in the Jan. 25 issue of Circulation.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but among adolescents with at least 85th percentile of body mass index and thus considered overweight/obese, added sugar intake was positively correlated with the homeostasis model assessment (HOMA-IR), which is an estimate of insulin resistance derived from fasting glucose and insulin levels, the investigators found (Circulation 2011 Jan. 25 [doi:10.1161/CIRCULATIONAHA.110972166]).

Adjusted mean HOMA-IR (fasting insulin [pmol/L] times fasting glucose [mmol/L]/22.5) in overweight adolescents was 4.61 in those with the highest added sugar consumption, compared with 3.49 in those with the lowest consumption.

The findings contribute to a growing body of evidence linking carbohydrate and sugar intake with increased cardiovascular disease risk and are particularly important given that consumption of added sugars has increased substantially in recent decades. In 1977-1978, daily consumption of added sugars among adolescents was 62g-84 g, compared with the nearly 119 g seen in this study, representing an increase of 42%-92%, the investigators said.

Mechanisms that might explain the dysmetabolic effects of carbohydrates, and specifically sugars, include the insulin response to the metabolism of high-glycemic index foods, the increased de novo lipogenesis that results when high levels of fructose are metabolized by the liver, and the increased hepatic triglyceride synthesis combined with increased secretion and/or decreased clearance of very low-density lipoproteins, the investigators wrote.

"Modification of the effect of added sugars on measures of glucose metabolism by weight status could be explained by the decreased insulin sensitivity known to result from increased adiposity," they added.

Adolescents in this study were U.S. residents aged 12-18 years who were randomly selected to provide a fasting blood sample for NHANES 1999-2004 and who provided dietary intake information. Those with unreliable or implausible dietary data were excluded, as were those who were pregnant, those who had extreme triglyceride levels, those with previously diagnosed diabetes mellitus, and those with missing covariate data. Dietary information was merged with U.S. Department of Agriculture MyPyramid equivalents databases to determine added sugar content.

The findings support the need for dietary guidelines that call for a lower intake of added sugars, and they highlight the need for additional study as well as "comprehensive examination" of the existing evidence on the effects of added sugars on cardiovascular and other chronic disease risks, the investigators said.

The findings also suggest that minimizing added sugar consumption in adolescents might reduce their future cardiovascular disease risk, they noted.

Dr. Miriam Vos, an author on the study, disclosed receiving financial support in the form of a career award from the National Institutes of Diabetes and Digestive and Kidney Diseases and also receiving support from the Children’s Digestive Health and Nutrition Foundation. Dr. Vos also is the author of "The No-Diet Obesity Solution for Kids," (Bethesda, Md.: AGA Institute Press, 2009) for which she receives royalties. The remaining authors report no relevant financial conflicts of interest.

Intake of added sugars among adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased high-density lipoprotein cholesterol levels, and increased low-density lipoprotein cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

© sjlocke/istock.com

In 2,157 adolescents who participated in the survey, the daily consumption of added sugars – defined as refined calorie–containing sweeteners added to food and beverages during processing or preparation – averaged 118.9 g (28.3 tsp. or 476 calories), representing an average of 21.4% of total energy. Among those with the highest level of added sugar intake (greater than or equal to 30% of total energy or greater) and the lowest level of added sugar intake (less than 10% of total energy), respectively, the HDL cholesterol levels were 1.28 and 1.40 mmol/L, LDL cholesterol levels were 2.44 and 2.24 mmol/L, and triglycerides were 0.89 and 0.81 mmol/L, Jean A. Welsh of Emory University, Atlanta, and her colleagues reported online in the Jan. 25 issue of Circulation.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but among adolescents with at least 85th percentile of body mass index and thus considered overweight/obese, added sugar intake was positively correlated with the homeostasis model assessment (HOMA-IR), which is an estimate of insulin resistance derived from fasting glucose and insulin levels, the investigators found (Circulation 2011 Jan. 25 [doi:10.1161/CIRCULATIONAHA.110972166]).

Adjusted mean HOMA-IR (fasting insulin [pmol/L] times fasting glucose [mmol/L]/22.5) in overweight adolescents was 4.61 in those with the highest added sugar consumption, compared with 3.49 in those with the lowest consumption.

The findings contribute to a growing body of evidence linking carbohydrate and sugar intake with increased cardiovascular disease risk and are particularly important given that consumption of added sugars has increased substantially in recent decades. In 1977-1978, daily consumption of added sugars among adolescents was 62g-84 g, compared with the nearly 119 g seen in this study, representing an increase of 42%-92%, the investigators said.

Mechanisms that might explain the dysmetabolic effects of carbohydrates, and specifically sugars, include the insulin response to the metabolism of high-glycemic index foods, the increased de novo lipogenesis that results when high levels of fructose are metabolized by the liver, and the increased hepatic triglyceride synthesis combined with increased secretion and/or decreased clearance of very low-density lipoproteins, the investigators wrote.

"Modification of the effect of added sugars on measures of glucose metabolism by weight status could be explained by the decreased insulin sensitivity known to result from increased adiposity," they added.

Adolescents in this study were U.S. residents aged 12-18 years who were randomly selected to provide a fasting blood sample for NHANES 1999-2004 and who provided dietary intake information. Those with unreliable or implausible dietary data were excluded, as were those who were pregnant, those who had extreme triglyceride levels, those with previously diagnosed diabetes mellitus, and those with missing covariate data. Dietary information was merged with U.S. Department of Agriculture MyPyramid equivalents databases to determine added sugar content.

The findings support the need for dietary guidelines that call for a lower intake of added sugars, and they highlight the need for additional study as well as "comprehensive examination" of the existing evidence on the effects of added sugars on cardiovascular and other chronic disease risks, the investigators said.

The findings also suggest that minimizing added sugar consumption in adolescents might reduce their future cardiovascular disease risk, they noted.

Dr. Miriam Vos, an author on the study, disclosed receiving financial support in the form of a career award from the National Institutes of Diabetes and Digestive and Kidney Diseases and also receiving support from the Children’s Digestive Health and Nutrition Foundation. Dr. Vos also is the author of "The No-Diet Obesity Solution for Kids," (Bethesda, Md.: AGA Institute Press, 2009) for which she receives royalties. The remaining authors report no relevant financial conflicts of interest.

Intake of added sugars among adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased high-density lipoprotein cholesterol levels, and increased low-density lipoprotein cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

© sjlocke/istock.com

In 2,157 adolescents who participated in the survey, the daily consumption of added sugars – defined as refined calorie–containing sweeteners added to food and beverages during processing or preparation – averaged 118.9 g (28.3 tsp. or 476 calories), representing an average of 21.4% of total energy. Among those with the highest level of added sugar intake (greater than or equal to 30% of total energy or greater) and the lowest level of added sugar intake (less than 10% of total energy), respectively, the HDL cholesterol levels were 1.28 and 1.40 mmol/L, LDL cholesterol levels were 2.44 and 2.24 mmol/L, and triglycerides were 0.89 and 0.81 mmol/L, Jean A. Welsh of Emory University, Atlanta, and her colleagues reported online in the Jan. 25 issue of Circulation.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but among adolescents with at least 85th percentile of body mass index and thus considered overweight/obese, added sugar intake was positively correlated with the homeostasis model assessment (HOMA-IR), which is an estimate of insulin resistance derived from fasting glucose and insulin levels, the investigators found (Circulation 2011 Jan. 25 [doi:10.1161/CIRCULATIONAHA.110972166]).

Adjusted mean HOMA-IR (fasting insulin [pmol/L] times fasting glucose [mmol/L]/22.5) in overweight adolescents was 4.61 in those with the highest added sugar consumption, compared with 3.49 in those with the lowest consumption.

The findings contribute to a growing body of evidence linking carbohydrate and sugar intake with increased cardiovascular disease risk and are particularly important given that consumption of added sugars has increased substantially in recent decades. In 1977-1978, daily consumption of added sugars among adolescents was 62g-84 g, compared with the nearly 119 g seen in this study, representing an increase of 42%-92%, the investigators said.

Mechanisms that might explain the dysmetabolic effects of carbohydrates, and specifically sugars, include the insulin response to the metabolism of high-glycemic index foods, the increased de novo lipogenesis that results when high levels of fructose are metabolized by the liver, and the increased hepatic triglyceride synthesis combined with increased secretion and/or decreased clearance of very low-density lipoproteins, the investigators wrote.

"Modification of the effect of added sugars on measures of glucose metabolism by weight status could be explained by the decreased insulin sensitivity known to result from increased adiposity," they added.

Adolescents in this study were U.S. residents aged 12-18 years who were randomly selected to provide a fasting blood sample for NHANES 1999-2004 and who provided dietary intake information. Those with unreliable or implausible dietary data were excluded, as were those who were pregnant, those who had extreme triglyceride levels, those with previously diagnosed diabetes mellitus, and those with missing covariate data. Dietary information was merged with U.S. Department of Agriculture MyPyramid equivalents databases to determine added sugar content.

The findings support the need for dietary guidelines that call for a lower intake of added sugars, and they highlight the need for additional study as well as "comprehensive examination" of the existing evidence on the effects of added sugars on cardiovascular and other chronic disease risks, the investigators said.

The findings also suggest that minimizing added sugar consumption in adolescents might reduce their future cardiovascular disease risk, they noted.

Dr. Miriam Vos, an author on the study, disclosed receiving financial support in the form of a career award from the National Institutes of Diabetes and Digestive and Kidney Diseases and also receiving support from the Children’s Digestive Health and Nutrition Foundation. Dr. Vos also is the author of "The No-Diet Obesity Solution for Kids," (Bethesda, Md.: AGA Institute Press, 2009) for which she receives royalties. The remaining authors report no relevant financial conflicts of interest.

Intake of added sugars among adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased high-density lipoprotein cholesterol levels, and increased low-density lipoprotein cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

© sjlocke/istock.com

In 2,157 adolescents who participated in the survey, the daily consumption of added sugars – defined as refined calorie–containing sweeteners added to food and beverages during processing or preparation – averaged 118.9 g (28.3 tsp. or 476 calories), representing an average of 21.4% of total energy. Among those with the highest level of added sugar intake (greater than or equal to 30% of total energy or greater) and the lowest level of added sugar intake (less than 10% of total energy), respectively, the HDL cholesterol levels were 1.28 and 1.40 mmol/L, LDL cholesterol levels were 2.44 and 2.24 mmol/L, and triglycerides were 0.89 and 0.81 mmol/L, Jean A. Welsh of Emory University, Atlanta, and her colleagues reported online in the Jan. 25 issue of Circulation.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but among adolescents with at least 85th percentile of body mass index and thus considered overweight/obese, added sugar intake was positively correlated with the homeostasis model assessment (HOMA-IR), which is an estimate of insulin resistance derived from fasting glucose and insulin levels, the investigators found (Circulation 2011 Jan. 25 [doi:10.1161/CIRCULATIONAHA.110972166]).

Adjusted mean HOMA-IR (fasting insulin [pmol/L] times fasting glucose [mmol/L]/22.5) in overweight adolescents was 4.61 in those with the highest added sugar consumption, compared with 3.49 in those with the lowest consumption.

The findings contribute to a growing body of evidence linking carbohydrate and sugar intake with increased cardiovascular disease risk and are particularly important given that consumption of added sugars has increased substantially in recent decades. In 1977-1978, daily consumption of added sugars among adolescents was 62g-84 g, compared with the nearly 119 g seen in this study, representing an increase of 42%-92%, the investigators said.

Mechanisms that might explain the dysmetabolic effects of carbohydrates, and specifically sugars, include the insulin response to the metabolism of high-glycemic index foods, the increased de novo lipogenesis that results when high levels of fructose are metabolized by the liver, and the increased hepatic triglyceride synthesis combined with increased secretion and/or decreased clearance of very low-density lipoproteins, the investigators wrote.

"Modification of the effect of added sugars on measures of glucose metabolism by weight status could be explained by the decreased insulin sensitivity known to result from increased adiposity," they added.

Adolescents in this study were U.S. residents aged 12-18 years who were randomly selected to provide a fasting blood sample for NHANES 1999-2004 and who provided dietary intake information. Those with unreliable or implausible dietary data were excluded, as were those who were pregnant, those who had extreme triglyceride levels, those with previously diagnosed diabetes mellitus, and those with missing covariate data. Dietary information was merged with U.S. Department of Agriculture MyPyramid equivalents databases to determine added sugar content.

The findings support the need for dietary guidelines that call for a lower intake of added sugars, and they highlight the need for additional study as well as "comprehensive examination" of the existing evidence on the effects of added sugars on cardiovascular and other chronic disease risks, the investigators said.

The findings also suggest that minimizing added sugar consumption in adolescents might reduce their future cardiovascular disease risk, they noted.

Dr. Miriam Vos, an author on the study, disclosed receiving financial support in the form of a career award from the National Institutes of Diabetes and Digestive and Kidney Diseases and also receiving support from the Children’s Digestive Health and Nutrition Foundation. Dr. Vos also is the author of "The No-Diet Obesity Solution for Kids," (Bethesda, Md.: AGA Institute Press, 2009) for which she receives royalties. The remaining authors report no relevant financial conflicts of interest.

ATLANTA – Treating chronic pain poses unique challenges in this age of abuse and litigation, but using contracts can help improve the chances that patients get the relief they need from opioid therapy – safely and without legal ramifications, according to Dr. Allan Gibofsky.

Before you get to the point of discussing a contract, however, it is important to assess a patient’s risk for problematic medication use and substance abuse. Several validated measures exist for this purpose (although none are in widespread use), and other methods can also be used to help predict potential problems, said Dr. Gibofsky, professor of medicine and public health at Weill Cornell Medical College and an attending rheumatologist at the Hospital for Special Surgery, New York.

For example, prior history of problematic use, requests for increased dosage, a preference for a specific route of administration, patient focus on opioids during a visit, multiple calls from the patient regarding prescriptions, prescription "loss" or "theft," and obtaining the same prescription from multiple sources are all signs of trouble, he noted.

Other factors that might be useful to consider in evaluating whether a patient should be treated or referred to an addiction specialist or pain management specialist include family history, psychiatric pathology, current status of substance abuse in others’ eyes, a history of physical or sexual abuse, an environment that includes others who meet some of these risk criteria, a chaotic home environment, and a family history of major psychiatric pathology.

A determination should be made as to whether the patient should be treated or referred to a pain management or addiction specialist for care, Dr. Gibofsky said, suggesting that if the choice is to treat, then the patient should be categorized into a low or high perceived-risk category, and therapy should be structured from that perspective.

"That will help your ability to monitor the patient and help a patient who may have some vulnerability maintain control," he said.

A contract should be considered as a way for the physicians and patients to achieve those goals.

It is reasonable – though sometimes challenging – to request all medical records and to contact all other health care providers to obtain prescribing and other histories, as well as to suggest, or even require, that a patient receive a consultation with a specialist if there is concern about abuse or potential risk of abuse.

The contract can also spell out what is expected of both the patient and the provider, and it can provide for penalties on both sides for violations. For example, a contract can require that a patient be seen on a certain schedule, and it can state that only small amounts of medication will be given, that toxicology screens must be performed, and that prescriptions won’t be refilled without a verifiable reason, he explained.

A contract could also require that concomitant nonpharmacologic modalities – that could limit the required dosing of pain medications – be used, and that others, such as a spouse or significant other, be allowed to contact you regarding the patient’s compliance, he said.

Such contracts are recommended by many pain management specialists, and they have been widely adopted, but they remain controversial. While they can be educational and can provide clarification of roles, patients may perceive them as stigmatizing and punitive. They can limit flexibility and – ironically – can increase liability for providers who don’t live up to their own responsibilities as specified in the contract.

However, they can also provide a good framework from which to provide safe and effective pain management.

In patients whose drug use has become aberrant, the contract can allow for appropriate intervention or interruption of care. Depending on the factors driving the behavior, it may be appropriate to refer the patient for consultation with a specialist, or to confront the patient and terminate care; aberrant behaviors can be driven by a number of factors, including addiction or plain criminal behavior.

If therapy is continued, consider the patient to be in a reassessment stage. Restructuring of therapy, coordination with other providers, reinitiation of a contract, and/or more frequent visits may be appropriate.

"Patients with behaviors out of control or that cannot be brought quickly under control are patients who should not be treated," Dr. Gibofsky said, adding that enabling patients is placing them in harm’s way, and that is not only placing yourself in harm’s way, it is also "not engaging in the best practice of our profession."

Patients who can’t accept the structure of treatment also should not be treated, he said, adding that "the issues surrounding long-term opioid therapy are significant, and offer great promise, but also great risk."

With appropriate risk assessment and management, pain can, however, be managed effectively, he concluded.

Dr. Gibofsky reported that he had no financial conflicts of interest relevant to this presentation.

ATLANTA – Treating chronic pain poses unique challenges in this age of abuse and litigation, but using contracts can help improve the chances that patients get the relief they need from opioid therapy – safely and without legal ramifications, according to Dr. Allan Gibofsky.

Before you get to the point of discussing a contract, however, it is important to assess a patient’s risk for problematic medication use and substance abuse. Several validated measures exist for this purpose (although none are in widespread use), and other methods can also be used to help predict potential problems, said Dr. Gibofsky, professor of medicine and public health at Weill Cornell Medical College and an attending rheumatologist at the Hospital for Special Surgery, New York.

For example, prior history of problematic use, requests for increased dosage, a preference for a specific route of administration, patient focus on opioids during a visit, multiple calls from the patient regarding prescriptions, prescription "loss" or "theft," and obtaining the same prescription from multiple sources are all signs of trouble, he noted.

Other factors that might be useful to consider in evaluating whether a patient should be treated or referred to an addiction specialist or pain management specialist include family history, psychiatric pathology, current status of substance abuse in others’ eyes, a history of physical or sexual abuse, an environment that includes others who meet some of these risk criteria, a chaotic home environment, and a family history of major psychiatric pathology.

A determination should be made as to whether the patient should be treated or referred to a pain management or addiction specialist for care, Dr. Gibofsky said, suggesting that if the choice is to treat, then the patient should be categorized into a low or high perceived-risk category, and therapy should be structured from that perspective.

"That will help your ability to monitor the patient and help a patient who may have some vulnerability maintain control," he said.

A contract should be considered as a way for the physicians and patients to achieve those goals.

It is reasonable – though sometimes challenging – to request all medical records and to contact all other health care providers to obtain prescribing and other histories, as well as to suggest, or even require, that a patient receive a consultation with a specialist if there is concern about abuse or potential risk of abuse.

The contract can also spell out what is expected of both the patient and the provider, and it can provide for penalties on both sides for violations. For example, a contract can require that a patient be seen on a certain schedule, and it can state that only small amounts of medication will be given, that toxicology screens must be performed, and that prescriptions won’t be refilled without a verifiable reason, he explained.

A contract could also require that concomitant nonpharmacologic modalities – that could limit the required dosing of pain medications – be used, and that others, such as a spouse or significant other, be allowed to contact you regarding the patient’s compliance, he said.

Such contracts are recommended by many pain management specialists, and they have been widely adopted, but they remain controversial. While they can be educational and can provide clarification of roles, patients may perceive them as stigmatizing and punitive. They can limit flexibility and – ironically – can increase liability for providers who don’t live up to their own responsibilities as specified in the contract.

However, they can also provide a good framework from which to provide safe and effective pain management.

In patients whose drug use has become aberrant, the contract can allow for appropriate intervention or interruption of care. Depending on the factors driving the behavior, it may be appropriate to refer the patient for consultation with a specialist, or to confront the patient and terminate care; aberrant behaviors can be driven by a number of factors, including addiction or plain criminal behavior.

If therapy is continued, consider the patient to be in a reassessment stage. Restructuring of therapy, coordination with other providers, reinitiation of a contract, and/or more frequent visits may be appropriate.

"Patients with behaviors out of control or that cannot be brought quickly under control are patients who should not be treated," Dr. Gibofsky said, adding that enabling patients is placing them in harm’s way, and that is not only placing yourself in harm’s way, it is also "not engaging in the best practice of our profession."

Patients who can’t accept the structure of treatment also should not be treated, he said, adding that "the issues surrounding long-term opioid therapy are significant, and offer great promise, but also great risk."

With appropriate risk assessment and management, pain can, however, be managed effectively, he concluded.

Dr. Gibofsky reported that he had no financial conflicts of interest relevant to this presentation.

ATLANTA – Treating chronic pain poses unique challenges in this age of abuse and litigation, but using contracts can help improve the chances that patients get the relief they need from opioid therapy – safely and without legal ramifications, according to Dr. Allan Gibofsky.

Before you get to the point of discussing a contract, however, it is important to assess a patient’s risk for problematic medication use and substance abuse. Several validated measures exist for this purpose (although none are in widespread use), and other methods can also be used to help predict potential problems, said Dr. Gibofsky, professor of medicine and public health at Weill Cornell Medical College and an attending rheumatologist at the Hospital for Special Surgery, New York.

For example, prior history of problematic use, requests for increased dosage, a preference for a specific route of administration, patient focus on opioids during a visit, multiple calls from the patient regarding prescriptions, prescription "loss" or "theft," and obtaining the same prescription from multiple sources are all signs of trouble, he noted.

Other factors that might be useful to consider in evaluating whether a patient should be treated or referred to an addiction specialist or pain management specialist include family history, psychiatric pathology, current status of substance abuse in others’ eyes, a history of physical or sexual abuse, an environment that includes others who meet some of these risk criteria, a chaotic home environment, and a family history of major psychiatric pathology.

A determination should be made as to whether the patient should be treated or referred to a pain management or addiction specialist for care, Dr. Gibofsky said, suggesting that if the choice is to treat, then the patient should be categorized into a low or high perceived-risk category, and therapy should be structured from that perspective.

"That will help your ability to monitor the patient and help a patient who may have some vulnerability maintain control," he said.

A contract should be considered as a way for the physicians and patients to achieve those goals.

It is reasonable – though sometimes challenging – to request all medical records and to contact all other health care providers to obtain prescribing and other histories, as well as to suggest, or even require, that a patient receive a consultation with a specialist if there is concern about abuse or potential risk of abuse.

The contract can also spell out what is expected of both the patient and the provider, and it can provide for penalties on both sides for violations. For example, a contract can require that a patient be seen on a certain schedule, and it can state that only small amounts of medication will be given, that toxicology screens must be performed, and that prescriptions won’t be refilled without a verifiable reason, he explained.

A contract could also require that concomitant nonpharmacologic modalities – that could limit the required dosing of pain medications – be used, and that others, such as a spouse or significant other, be allowed to contact you regarding the patient’s compliance, he said.

Such contracts are recommended by many pain management specialists, and they have been widely adopted, but they remain controversial. While they can be educational and can provide clarification of roles, patients may perceive them as stigmatizing and punitive. They can limit flexibility and – ironically – can increase liability for providers who don’t live up to their own responsibilities as specified in the contract.

However, they can also provide a good framework from which to provide safe and effective pain management.

In patients whose drug use has become aberrant, the contract can allow for appropriate intervention or interruption of care. Depending on the factors driving the behavior, it may be appropriate to refer the patient for consultation with a specialist, or to confront the patient and terminate care; aberrant behaviors can be driven by a number of factors, including addiction or plain criminal behavior.

If therapy is continued, consider the patient to be in a reassessment stage. Restructuring of therapy, coordination with other providers, reinitiation of a contract, and/or more frequent visits may be appropriate.

"Patients with behaviors out of control or that cannot be brought quickly under control are patients who should not be treated," Dr. Gibofsky said, adding that enabling patients is placing them in harm’s way, and that is not only placing yourself in harm’s way, it is also "not engaging in the best practice of our profession."

Patients who can’t accept the structure of treatment also should not be treated, he said, adding that "the issues surrounding long-term opioid therapy are significant, and offer great promise, but also great risk."

With appropriate risk assessment and management, pain can, however, be managed effectively, he concluded.

Dr. Gibofsky reported that he had no financial conflicts of interest relevant to this presentation.

Major Finding: Patients taking 7 mg/day or 14 mg/day of teriflunomide experienced a statistically significant 31% reduction in the annualized relapse rate.

Data Source: A randomized, placebo-controlled phase III study (TEMSO) involving 1,088 patients with relapsing MS.

Disclosures: Sanofi-Aventis sponsored the trial. The investigators disclosed financial relationships with many companies that manufacture drugs for MS, including Sanofi-Aventis.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a significant reduction of 31% compared with placebo. The 14-mg group also showed a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. The teriflunomide group had more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18–55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course … we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

Major Finding: Patients taking 7 mg/day or 14 mg/day of teriflunomide experienced a statistically significant 31% reduction in the annualized relapse rate.

Data Source: A randomized, placebo-controlled phase III study (TEMSO) involving 1,088 patients with relapsing MS.

Disclosures: Sanofi-Aventis sponsored the trial. The investigators disclosed financial relationships with many companies that manufacture drugs for MS, including Sanofi-Aventis.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a significant reduction of 31% compared with placebo. The 14-mg group also showed a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. The teriflunomide group had more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18–55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course … we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

Major Finding: Patients taking 7 mg/day or 14 mg/day of teriflunomide experienced a statistically significant 31% reduction in the annualized relapse rate.

Data Source: A randomized, placebo-controlled phase III study (TEMSO) involving 1,088 patients with relapsing MS.

Disclosures: Sanofi-Aventis sponsored the trial. The investigators disclosed financial relationships with many companies that manufacture drugs for MS, including Sanofi-Aventis.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a significant reduction of 31% compared with placebo. The 14-mg group also showed a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. The teriflunomide group had more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18–55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course … we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

Major Finding: CDMS occurred in a significantly smaller percentage of patients who underwent early treatment with glatiramer acetate than in those who delayed treatment until 3 years later with the drug (33% vs. 50%).

Data Source: A 2-year extension of the 3-year double-blind, placebo-controlled PreCISe study of 198 patients

Disclosures: Teva Pharmaceutical Industries funded the trial. Dr. Comi reported that he has received honoraria for speaking activities and personal compensation for advisory board and consulting activities from Teva Pharmaceuticals and other MS drug manufacturers. Dr. Filippi also reported financial relationship with Teva and other MS drug manufacturers. Dr. Raman has received grants from the National Multiple Sclerosis Society and the National Institutes of Health.

Patients with clinically isolated syndrome who receive early treatment with glatiramer acetate have more than a 40% reduction in the risk of developing multiple sclerosis, compared with those whose treatment is delayed, according to findings from a prospectively planned 5-year follow-up of patient in the phase III PreCISe study.

After a 2-year extension phase of the 3-year double-blind, placebo-controlled study, 33% of 80 patients who had received early treatment with glatiramer acetate (GA) developed clinically definite multiple sclerosis (CDMS), compared with 50% of 118 patients who began treatment at the end of the initial 3-year double-blind phase. Each patient received 20 mg of GA daily by subcutaneous injection.

GA is marketed as Copaxone by Teva Pharmaceutical Industries. It is approved in 51 countries, including the United States, and is indicated for reducing the frequency of relapses in relapsing-remitting MS, including those who have experienced a first clinical episode and who have MS features on MRI.

In the Teva-sponsored study, disability progression, as measured by the Expanded Disability Status Scale, occurred in only 21% of patients over 5 years. No differences in progression were noted between the early and delayed treatment groups, according to the principal investigator, Dr. Giancarlo Comi, director of the department of neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy.

“The long-term study results support the benefit of early GA treatment in delaying conversion to CDMS and in reducing MRI burden, including less accumulation of irreversible brain damage,” Dr. Comi said in an interview.

Patients in this 2-year extension phase were initially enrolled in the double-blind phase of PreCISe, and were randomized to receive active early treatment with GA or placebo. Findings from a planned interim analysis showed that treatment reduced the risk of CDMS by 44% versus placebo, and delayed disease progression by 722 days vs. 336 days. That phase was stopped after a mean exposure of 2.32 years, and patients were offered the opportunity to enter the open-label extension phase, during which all patients received treatment.

Early treatment reduced the risk of CDMS and delayed its onset compared with placebo in the randomized phase of the trial, but also was associated in the open-label extension with a delay of nearly 3 years in the time to conversion to CDMS compared with delayed treatment.

MRI findings from the PreCISe study, which were presented in a separate session at ECTRIMS, also confirmed the importance of early treatment, according to the principal investigator for that portion of the study, Dr. Massimo Filippi, director of the Neuroimaging Research Unit and professor of clinical neurology at the Scientific Institute and University Ospedale San Raffaele, Milan, and his colleagues.

Early initiation of treatment with GA reduced disease activity and slowed the accumulation of brain atrophy over 5 years as demonstrated by MRI. The early treatment group had significantly fewer new T2 lesions – an indicator of disease activity – and lower T2 lesion volume – a predictor of disease progression – than did the delayed treatment group, the investigators found.

Percent change in brain volume was also significantly lower over the entire study period in patients who received early treatment with GA (−0.99% vs. −1.27%), they said.

The drop-out rate in the 5 years of the PreCISe study was 33% among treated patients, which attests to the established long-term safety profile in patients with relapsing-remitting disease, Dr. Comi said.

“It is very difficult to compare Copaxone to other interferons studied in CIS due to the differences in the type of patients included in each study, but basically the results are comparable, although only Copaxone showed an effect on brain atrophy after 5 years,” Dr. Comi said. He added that the efficacy and safety results of this study establish the importance of early treatment with this drug in CIS patients presenting with positive brain MRI.

Chander Raman, Ph.D., an MS researcher and associate professor of clinical immunology and rheumatology at the University of Alabama at Birmingham, said the PreCISe findings confirm what neurologists have started to believe about managing CIS in adults – that treatment at the first clinical diagnosis of CIS is preferable to delay full conversion.

Major Finding: CDMS occurred in a significantly smaller percentage of patients who underwent early treatment with glatiramer acetate than in those who delayed treatment until 3 years later with the drug (33% vs. 50%).

Data Source: A 2-year extension of the 3-year double-blind, placebo-controlled PreCISe study of 198 patients

Disclosures: Teva Pharmaceutical Industries funded the trial. Dr. Comi reported that he has received honoraria for speaking activities and personal compensation for advisory board and consulting activities from Teva Pharmaceuticals and other MS drug manufacturers. Dr. Filippi also reported financial relationship with Teva and other MS drug manufacturers. Dr. Raman has received grants from the National Multiple Sclerosis Society and the National Institutes of Health.

Patients with clinically isolated syndrome who receive early treatment with glatiramer acetate have more than a 40% reduction in the risk of developing multiple sclerosis, compared with those whose treatment is delayed, according to findings from a prospectively planned 5-year follow-up of patient in the phase III PreCISe study.

After a 2-year extension phase of the 3-year double-blind, placebo-controlled study, 33% of 80 patients who had received early treatment with glatiramer acetate (GA) developed clinically definite multiple sclerosis (CDMS), compared with 50% of 118 patients who began treatment at the end of the initial 3-year double-blind phase. Each patient received 20 mg of GA daily by subcutaneous injection.

GA is marketed as Copaxone by Teva Pharmaceutical Industries. It is approved in 51 countries, including the United States, and is indicated for reducing the frequency of relapses in relapsing-remitting MS, including those who have experienced a first clinical episode and who have MS features on MRI.

In the Teva-sponsored study, disability progression, as measured by the Expanded Disability Status Scale, occurred in only 21% of patients over 5 years. No differences in progression were noted between the early and delayed treatment groups, according to the principal investigator, Dr. Giancarlo Comi, director of the department of neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy.

“The long-term study results support the benefit of early GA treatment in delaying conversion to CDMS and in reducing MRI burden, including less accumulation of irreversible brain damage,” Dr. Comi said in an interview.

Patients in this 2-year extension phase were initially enrolled in the double-blind phase of PreCISe, and were randomized to receive active early treatment with GA or placebo. Findings from a planned interim analysis showed that treatment reduced the risk of CDMS by 44% versus placebo, and delayed disease progression by 722 days vs. 336 days. That phase was stopped after a mean exposure of 2.32 years, and patients were offered the opportunity to enter the open-label extension phase, during which all patients received treatment.

Early treatment reduced the risk of CDMS and delayed its onset compared with placebo in the randomized phase of the trial, but also was associated in the open-label extension with a delay of nearly 3 years in the time to conversion to CDMS compared with delayed treatment.

MRI findings from the PreCISe study, which were presented in a separate session at ECTRIMS, also confirmed the importance of early treatment, according to the principal investigator for that portion of the study, Dr. Massimo Filippi, director of the Neuroimaging Research Unit and professor of clinical neurology at the Scientific Institute and University Ospedale San Raffaele, Milan, and his colleagues.

Early initiation of treatment with GA reduced disease activity and slowed the accumulation of brain atrophy over 5 years as demonstrated by MRI. The early treatment group had significantly fewer new T2 lesions – an indicator of disease activity – and lower T2 lesion volume – a predictor of disease progression – than did the delayed treatment group, the investigators found.

Percent change in brain volume was also significantly lower over the entire study period in patients who received early treatment with GA (−0.99% vs. −1.27%), they said.

The drop-out rate in the 5 years of the PreCISe study was 33% among treated patients, which attests to the established long-term safety profile in patients with relapsing-remitting disease, Dr. Comi said.

“It is very difficult to compare Copaxone to other interferons studied in CIS due to the differences in the type of patients included in each study, but basically the results are comparable, although only Copaxone showed an effect on brain atrophy after 5 years,” Dr. Comi said. He added that the efficacy and safety results of this study establish the importance of early treatment with this drug in CIS patients presenting with positive brain MRI.

Chander Raman, Ph.D., an MS researcher and associate professor of clinical immunology and rheumatology at the University of Alabama at Birmingham, said the PreCISe findings confirm what neurologists have started to believe about managing CIS in adults – that treatment at the first clinical diagnosis of CIS is preferable to delay full conversion.

Major Finding: CDMS occurred in a significantly smaller percentage of patients who underwent early treatment with glatiramer acetate than in those who delayed treatment until 3 years later with the drug (33% vs. 50%).

Data Source: A 2-year extension of the 3-year double-blind, placebo-controlled PreCISe study of 198 patients

Disclosures: Teva Pharmaceutical Industries funded the trial. Dr. Comi reported that he has received honoraria for speaking activities and personal compensation for advisory board and consulting activities from Teva Pharmaceuticals and other MS drug manufacturers. Dr. Filippi also reported financial relationship with Teva and other MS drug manufacturers. Dr. Raman has received grants from the National Multiple Sclerosis Society and the National Institutes of Health.

Patients with clinically isolated syndrome who receive early treatment with glatiramer acetate have more than a 40% reduction in the risk of developing multiple sclerosis, compared with those whose treatment is delayed, according to findings from a prospectively planned 5-year follow-up of patient in the phase III PreCISe study.

After a 2-year extension phase of the 3-year double-blind, placebo-controlled study, 33% of 80 patients who had received early treatment with glatiramer acetate (GA) developed clinically definite multiple sclerosis (CDMS), compared with 50% of 118 patients who began treatment at the end of the initial 3-year double-blind phase. Each patient received 20 mg of GA daily by subcutaneous injection.

GA is marketed as Copaxone by Teva Pharmaceutical Industries. It is approved in 51 countries, including the United States, and is indicated for reducing the frequency of relapses in relapsing-remitting MS, including those who have experienced a first clinical episode and who have MS features on MRI.

In the Teva-sponsored study, disability progression, as measured by the Expanded Disability Status Scale, occurred in only 21% of patients over 5 years. No differences in progression were noted between the early and delayed treatment groups, according to the principal investigator, Dr. Giancarlo Comi, director of the department of neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy.

“The long-term study results support the benefit of early GA treatment in delaying conversion to CDMS and in reducing MRI burden, including less accumulation of irreversible brain damage,” Dr. Comi said in an interview.

Patients in this 2-year extension phase were initially enrolled in the double-blind phase of PreCISe, and were randomized to receive active early treatment with GA or placebo. Findings from a planned interim analysis showed that treatment reduced the risk of CDMS by 44% versus placebo, and delayed disease progression by 722 days vs. 336 days. That phase was stopped after a mean exposure of 2.32 years, and patients were offered the opportunity to enter the open-label extension phase, during which all patients received treatment.

Early treatment reduced the risk of CDMS and delayed its onset compared with placebo in the randomized phase of the trial, but also was associated in the open-label extension with a delay of nearly 3 years in the time to conversion to CDMS compared with delayed treatment.

MRI findings from the PreCISe study, which were presented in a separate session at ECTRIMS, also confirmed the importance of early treatment, according to the principal investigator for that portion of the study, Dr. Massimo Filippi, director of the Neuroimaging Research Unit and professor of clinical neurology at the Scientific Institute and University Ospedale San Raffaele, Milan, and his colleagues.

Early initiation of treatment with GA reduced disease activity and slowed the accumulation of brain atrophy over 5 years as demonstrated by MRI. The early treatment group had significantly fewer new T2 lesions – an indicator of disease activity – and lower T2 lesion volume – a predictor of disease progression – than did the delayed treatment group, the investigators found.

Percent change in brain volume was also significantly lower over the entire study period in patients who received early treatment with GA (−0.99% vs. −1.27%), they said.

The drop-out rate in the 5 years of the PreCISe study was 33% among treated patients, which attests to the established long-term safety profile in patients with relapsing-remitting disease, Dr. Comi said.

“It is very difficult to compare Copaxone to other interferons studied in CIS due to the differences in the type of patients included in each study, but basically the results are comparable, although only Copaxone showed an effect on brain atrophy after 5 years,” Dr. Comi said. He added that the efficacy and safety results of this study establish the importance of early treatment with this drug in CIS patients presenting with positive brain MRI.

Chander Raman, Ph.D., an MS researcher and associate professor of clinical immunology and rheumatology at the University of Alabama at Birmingham, said the PreCISe findings confirm what neurologists have started to believe about managing CIS in adults – that treatment at the first clinical diagnosis of CIS is preferable to delay full conversion.

ATLANTA — Getting to the place in rheumatoid arthritis therapy where remission is a possibility has been much like the process of conquering a treacherous mountain, according to Dr. Duncan Porter.

Early climbers struggled and failed, but lessons were learned, better equipment was developed, and those who followed in the footsteps of the pioneers achieved what was once thought to be impossible.

“In rheumatology, we have had our own mountain to climb: Twenty years ago we were still puttering around in the foothills with symptom control, through the '80s and '90s we were developing increasing evidence that confirmed that conventional disease-modifying drugs … truly did modify disease activity, but it's been only recently that we've come to focus on the possibility of achieving remission,” he said at the meeting.

Now the top of the mountain is being reached “a good deal more often and a good deal more quickly,” he said, citing findings from the Dutch Rheumatoid Arthritis Monitoring (DREAM) cohort study, which were also presented at the meeting, showing that in 64% of 534 patients with newly diagnosed RA, remission was rapidly achieved with a tight control treatment strategy (Arthritis Rheum. 2010;62[suppl.]:abstract 662).

“I think the reason we're getting there is because we've got better equipment, so we've got more drugs to employ,” Dr. Porter said, adding that although the “better equipment” includes biologics, the improvements are primarily due to the new strategies of care.

“It's how we attack the mountain, it's how we deploy the drugs that we have that has yielded the greatest improvements in outcome,” said Dr. Porter of the University of Glasgow (Scotland).

The treatment strategies he discussed included intensive management, treatment to target, combination disease-modifying anti-rheumatic drug (DMARD) strategies, and remission induction.

Although intensive management and treatment to target often overlap, they are not the same, he stressed.

Intensive management, using monthly patient visits, liberal intramuscular and intra-articular steroid injections, escalation of therapy for persistent disease, and step-up dosing, has been shown to be highly effective for inducing remission. In the TICORA (Tight Control for Rheumatoid Arthritis) study (Lancet 2004;364:263-9), for example, 65% of patients achieved remission, compared with 16% of patients who did not receive intensive management.

Treatment to target was a component of that study, but treatment to target doesn't necessarily include intensive management components, Dr. Porter explained, adding, “I think that may be significant.”

Nonetheless, a recent literature review concluded that although few studies have used a randomized approach to test the value of treatment to target strategies, there is “unanimous” and “compelling” evidence that targeted approaches have value (Ann. Rheum. Dis. 2010;69:638-43).

With a treatment to target strategy, it is important to measure progress toward the target and to adjust therapy accordingly based on clinical judgment. Targets can be based on disease activity scores, or they can be based on remission, ultrasound findings, or biomarkers.

“If nothing else, using [the] disease activity score and applying it to treat to target and intensive management strategies has simply been proven to work,” Dr. Porter said, adding that “starting [patients] on methotrexate and sending them away for 6 months is no longer acceptable.”

Because most studies use a constant dose of the study drug, interpretation in terms of treatment to target strategies can be difficult, as that's not the way treatment to target works, and it's not the way most physicians practice, he said.

“Keeping that in mind is critical if we're to … come to the best strategy,” he added.

One area where it is important to make a distinction between intensive management and treatment to target is with the third strategy Dr. Porter discussed: the combined use of DMARDs. These can include step-up, step-down, and parallel therapy.

In the Bone Estrogen Strength Training (BEST) study, for example, treatment to target, but not intensive management, was used. Four strategies were evaluated, including sequential monotherapy, step-up combination therapy, initial combination therapy plus steroids, and initial biologic therapy.

At 2 years, the groups were identical, and importantly, 39% of patients had sustained low disease activity on monotherapy (Arthritis Rheum. 2005;52:3381-90).

“I think that's quite important if we're to avoid overtreating patients with multiple drugs when they will just do fine on one drug alone,” he said.

Other studies have compared various combinations, and showed that nothing is lost in waiting to see whether combination therapy versus monotherapy is needed. As for the use of biologics, the decision must be based on the complex synthesis of knowledge about efficacy, toxicity, and cost.

A key factor – and a challenge – is knowing the clinical significance of small numbers of Sharp score changes, particularly when you recognize that there is no evidence at all of a window of opportunity when it comes to biologic therapy and halting radiographic progression, Dr. Porter said.

The final strategy – remission induction – remains largely uncharacterized, he said, noting that there are few good studies, and more definitive research is needed to clarify its role.

“By and large we need to maintain the therapies we've started that get our patients into remission, and by and large we cannot plan to withdraw therapies large scale. … There's little compelling evidence, as far as I can see, of early aggressive therapy of any form that can substantially and permanently modify disease processes such that therapy can be withdrawn,” Dr. Porter said.

That suggests rheumatologists are doing much better than 20 years ago in terms of climbing the RA therapy mountain but that the summit has not been reached. And if the RA therapy goals of drug-free remission, cure, and prevention are added to that mountain – which currently has symptom control at its base, followed by disease modification and remission, then half of the mountain remains to be conquered.

In conclusion, Dr. Porter quoted a recent editorial that accompanied another DMARD combination trial (Lancet 2009;374:430-2):

“The most important information to be gathered from clinical trials in RA is not necessarily comparison of agents, but rather the strategy of tight control aiming for remission.”

Dr. Porter said that he has received research funding, served as a consultant, and/or served on the speakers bureau for Abbott, Pfizer, Roche, Schering Plough, and UCB.

ATLANTA — Getting to the place in rheumatoid arthritis therapy where remission is a possibility has been much like the process of conquering a treacherous mountain, according to Dr. Duncan Porter.

Early climbers struggled and failed, but lessons were learned, better equipment was developed, and those who followed in the footsteps of the pioneers achieved what was once thought to be impossible.

“In rheumatology, we have had our own mountain to climb: Twenty years ago we were still puttering around in the foothills with symptom control, through the '80s and '90s we were developing increasing evidence that confirmed that conventional disease-modifying drugs … truly did modify disease activity, but it's been only recently that we've come to focus on the possibility of achieving remission,” he said at the meeting.

Now the top of the mountain is being reached “a good deal more often and a good deal more quickly,” he said, citing findings from the Dutch Rheumatoid Arthritis Monitoring (DREAM) cohort study, which were also presented at the meeting, showing that in 64% of 534 patients with newly diagnosed RA, remission was rapidly achieved with a tight control treatment strategy (Arthritis Rheum. 2010;62[suppl.]:abstract 662).

“I think the reason we're getting there is because we've got better equipment, so we've got more drugs to employ,” Dr. Porter said, adding that although the “better equipment” includes biologics, the improvements are primarily due to the new strategies of care.

“It's how we attack the mountain, it's how we deploy the drugs that we have that has yielded the greatest improvements in outcome,” said Dr. Porter of the University of Glasgow (Scotland).

The treatment strategies he discussed included intensive management, treatment to target, combination disease-modifying anti-rheumatic drug (DMARD) strategies, and remission induction.

Although intensive management and treatment to target often overlap, they are not the same, he stressed.

Intensive management, using monthly patient visits, liberal intramuscular and intra-articular steroid injections, escalation of therapy for persistent disease, and step-up dosing, has been shown to be highly effective for inducing remission. In the TICORA (Tight Control for Rheumatoid Arthritis) study (Lancet 2004;364:263-9), for example, 65% of patients achieved remission, compared with 16% of patients who did not receive intensive management.

Treatment to target was a component of that study, but treatment to target doesn't necessarily include intensive management components, Dr. Porter explained, adding, “I think that may be significant.”

Nonetheless, a recent literature review concluded that although few studies have used a randomized approach to test the value of treatment to target strategies, there is “unanimous” and “compelling” evidence that targeted approaches have value (Ann. Rheum. Dis. 2010;69:638-43).

With a treatment to target strategy, it is important to measure progress toward the target and to adjust therapy accordingly based on clinical judgment. Targets can be based on disease activity scores, or they can be based on remission, ultrasound findings, or biomarkers.

“If nothing else, using [the] disease activity score and applying it to treat to target and intensive management strategies has simply been proven to work,” Dr. Porter said, adding that “starting [patients] on methotrexate and sending them away for 6 months is no longer acceptable.”

Because most studies use a constant dose of the study drug, interpretation in terms of treatment to target strategies can be difficult, as that's not the way treatment to target works, and it's not the way most physicians practice, he said.

“Keeping that in mind is critical if we're to … come to the best strategy,” he added.

One area where it is important to make a distinction between intensive management and treatment to target is with the third strategy Dr. Porter discussed: the combined use of DMARDs. These can include step-up, step-down, and parallel therapy.

In the Bone Estrogen Strength Training (BEST) study, for example, treatment to target, but not intensive management, was used. Four strategies were evaluated, including sequential monotherapy, step-up combination therapy, initial combination therapy plus steroids, and initial biologic therapy.

At 2 years, the groups were identical, and importantly, 39% of patients had sustained low disease activity on monotherapy (Arthritis Rheum. 2005;52:3381-90).

“I think that's quite important if we're to avoid overtreating patients with multiple drugs when they will just do fine on one drug alone,” he said.

Other studies have compared various combinations, and showed that nothing is lost in waiting to see whether combination therapy versus monotherapy is needed. As for the use of biologics, the decision must be based on the complex synthesis of knowledge about efficacy, toxicity, and cost.

A key factor – and a challenge – is knowing the clinical significance of small numbers of Sharp score changes, particularly when you recognize that there is no evidence at all of a window of opportunity when it comes to biologic therapy and halting radiographic progression, Dr. Porter said.

The final strategy – remission induction – remains largely uncharacterized, he said, noting that there are few good studies, and more definitive research is needed to clarify its role.

“By and large we need to maintain the therapies we've started that get our patients into remission, and by and large we cannot plan to withdraw therapies large scale. … There's little compelling evidence, as far as I can see, of early aggressive therapy of any form that can substantially and permanently modify disease processes such that therapy can be withdrawn,” Dr. Porter said.

That suggests rheumatologists are doing much better than 20 years ago in terms of climbing the RA therapy mountain but that the summit has not been reached. And if the RA therapy goals of drug-free remission, cure, and prevention are added to that mountain – which currently has symptom control at its base, followed by disease modification and remission, then half of the mountain remains to be conquered.

In conclusion, Dr. Porter quoted a recent editorial that accompanied another DMARD combination trial (Lancet 2009;374:430-2):

“The most important information to be gathered from clinical trials in RA is not necessarily comparison of agents, but rather the strategy of tight control aiming for remission.”

Dr. Porter said that he has received research funding, served as a consultant, and/or served on the speakers bureau for Abbott, Pfizer, Roche, Schering Plough, and UCB.

ATLANTA — Getting to the place in rheumatoid arthritis therapy where remission is a possibility has been much like the process of conquering a treacherous mountain, according to Dr. Duncan Porter.

Early climbers struggled and failed, but lessons were learned, better equipment was developed, and those who followed in the footsteps of the pioneers achieved what was once thought to be impossible.

“In rheumatology, we have had our own mountain to climb: Twenty years ago we were still puttering around in the foothills with symptom control, through the '80s and '90s we were developing increasing evidence that confirmed that conventional disease-modifying drugs … truly did modify disease activity, but it's been only recently that we've come to focus on the possibility of achieving remission,” he said at the meeting.

Now the top of the mountain is being reached “a good deal more often and a good deal more quickly,” he said, citing findings from the Dutch Rheumatoid Arthritis Monitoring (DREAM) cohort study, which were also presented at the meeting, showing that in 64% of 534 patients with newly diagnosed RA, remission was rapidly achieved with a tight control treatment strategy (Arthritis Rheum. 2010;62[suppl.]:abstract 662).

“I think the reason we're getting there is because we've got better equipment, so we've got more drugs to employ,” Dr. Porter said, adding that although the “better equipment” includes biologics, the improvements are primarily due to the new strategies of care.

“It's how we attack the mountain, it's how we deploy the drugs that we have that has yielded the greatest improvements in outcome,” said Dr. Porter of the University of Glasgow (Scotland).

The treatment strategies he discussed included intensive management, treatment to target, combination disease-modifying anti-rheumatic drug (DMARD) strategies, and remission induction.

Although intensive management and treatment to target often overlap, they are not the same, he stressed.

Intensive management, using monthly patient visits, liberal intramuscular and intra-articular steroid injections, escalation of therapy for persistent disease, and step-up dosing, has been shown to be highly effective for inducing remission. In the TICORA (Tight Control for Rheumatoid Arthritis) study (Lancet 2004;364:263-9), for example, 65% of patients achieved remission, compared with 16% of patients who did not receive intensive management.

Treatment to target was a component of that study, but treatment to target doesn't necessarily include intensive management components, Dr. Porter explained, adding, “I think that may be significant.”

Nonetheless, a recent literature review concluded that although few studies have used a randomized approach to test the value of treatment to target strategies, there is “unanimous” and “compelling” evidence that targeted approaches have value (Ann. Rheum. Dis. 2010;69:638-43).

With a treatment to target strategy, it is important to measure progress toward the target and to adjust therapy accordingly based on clinical judgment. Targets can be based on disease activity scores, or they can be based on remission, ultrasound findings, or biomarkers.

“If nothing else, using [the] disease activity score and applying it to treat to target and intensive management strategies has simply been proven to work,” Dr. Porter said, adding that “starting [patients] on methotrexate and sending them away for 6 months is no longer acceptable.”

Because most studies use a constant dose of the study drug, interpretation in terms of treatment to target strategies can be difficult, as that's not the way treatment to target works, and it's not the way most physicians practice, he said.

“Keeping that in mind is critical if we're to … come to the best strategy,” he added.

One area where it is important to make a distinction between intensive management and treatment to target is with the third strategy Dr. Porter discussed: the combined use of DMARDs. These can include step-up, step-down, and parallel therapy.

In the Bone Estrogen Strength Training (BEST) study, for example, treatment to target, but not intensive management, was used. Four strategies were evaluated, including sequential monotherapy, step-up combination therapy, initial combination therapy plus steroids, and initial biologic therapy.

At 2 years, the groups were identical, and importantly, 39% of patients had sustained low disease activity on monotherapy (Arthritis Rheum. 2005;52:3381-90).

“I think that's quite important if we're to avoid overtreating patients with multiple drugs when they will just do fine on one drug alone,” he said.

Other studies have compared various combinations, and showed that nothing is lost in waiting to see whether combination therapy versus monotherapy is needed. As for the use of biologics, the decision must be based on the complex synthesis of knowledge about efficacy, toxicity, and cost.

A key factor – and a challenge – is knowing the clinical significance of small numbers of Sharp score changes, particularly when you recognize that there is no evidence at all of a window of opportunity when it comes to biologic therapy and halting radiographic progression, Dr. Porter said.

The final strategy – remission induction – remains largely uncharacterized, he said, noting that there are few good studies, and more definitive research is needed to clarify its role.

“By and large we need to maintain the therapies we've started that get our patients into remission, and by and large we cannot plan to withdraw therapies large scale. … There's little compelling evidence, as far as I can see, of early aggressive therapy of any form that can substantially and permanently modify disease processes such that therapy can be withdrawn,” Dr. Porter said.

That suggests rheumatologists are doing much better than 20 years ago in terms of climbing the RA therapy mountain but that the summit has not been reached. And if the RA therapy goals of drug-free remission, cure, and prevention are added to that mountain – which currently has symptom control at its base, followed by disease modification and remission, then half of the mountain remains to be conquered.

In conclusion, Dr. Porter quoted a recent editorial that accompanied another DMARD combination trial (Lancet 2009;374:430-2):

“The most important information to be gathered from clinical trials in RA is not necessarily comparison of agents, but rather the strategy of tight control aiming for remission.”

Dr. Porter said that he has received research funding, served as a consultant, and/or served on the speakers bureau for Abbott, Pfizer, Roche, Schering Plough, and UCB.

Major Finding: After taking into consideration the propensity for prescribing methotrexate, prednisone, and anti–tumor necrosis factor agents over time, and after adjusting for potential confounding factors such as disease severity, a strong protective effect on mortality in RA patients was shown for methotrexate (adjusted hazard ratio 0.23) but not for prednisone (adjusted hazard ratio 1.80).

Data Source: An analysis of data – using a novel propensity scoring method – from a longitudinal multicenter observational database of 5,629 RA patients.

Disclosures: Dr. Wasko disclosed that she has received research grants from Amgen, has served as the principle investigator for clinical trials for Centocor, and has served as a consultant for Centocor and UCB.

ATLANTA — Methotrexate use is strongly associated with longer survival in rheumatoid arthritis patients.

After taking into consideration the propensity for prescribing methotrexate, prednisone, and anti–tumor necrosis factor (TNF) agents over time, and after adjusting for potential confounding factors such as disease severity, a strong protective effect on mortality was shown for methotrexate (adjusted hazard ratio 0.23) but not for prednisone (adjusted hazard ratio 1.80), said Dr. Mary Chester Wasko.

Combined treatment with methotrexate and prednisone also had a significant protective effect (hazard ratio 0.34).

“Since methotrexate appeared to be strongly protective with respect to survival in these analyses, and because methotrexate and prednisone are often prescribed together in practice, we questioned whether there might be an interaction between the two drugs with respect to survival,” said Dr. Wasko of the University of Pittsburgh.

Indeed, the strength of the association between methotrexate and improved mortality was only modestly reduced when methotrexate was used in combination with prednisone, she added.

Anti-TNF agents were associated with a slightly decreased risk of mortality. Although the result was not statistically significant (adjusted hazard ratio 0.15), follow-up was limited, as the analyses were based on only 10 deaths out of 598 treated patients with only 5 years of follow-up after these drugs were approved. Additional follow-up is needed to strengthen the results.

Dr. Wasko and her colleagues used the Arthritis, Rheumatism, and Aging Medical Information Systems (ARAMIS) database of patients from 10 U.S. rheumatology practices for their study. The median age of the 5,629 participants was 58 years, 75% were female, 90% were white, and follow-up was a median of 4 years and 3 months. A total of 1,027 patients died during 36,612 patient years of observation.

Patients were evaluated biannually from 1981 to 2003 using the Health Assessment Questionnaire (HAQ).

They reported on demographics, health status (including comorbidities), and medication use.

The outcome of interest was all-cause mortality as confirmed by next of kin.

Major Finding: After taking into consideration the propensity for prescribing methotrexate, prednisone, and anti–tumor necrosis factor agents over time, and after adjusting for potential confounding factors such as disease severity, a strong protective effect on mortality in RA patients was shown for methotrexate (adjusted hazard ratio 0.23) but not for prednisone (adjusted hazard ratio 1.80).

Data Source: An analysis of data – using a novel propensity scoring method – from a longitudinal multicenter observational database of 5,629 RA patients.

Disclosures: Dr. Wasko disclosed that she has received research grants from Amgen, has served as the principle investigator for clinical trials for Centocor, and has served as a consultant for Centocor and UCB.

ATLANTA — Methotrexate use is strongly associated with longer survival in rheumatoid arthritis patients.

After taking into consideration the propensity for prescribing methotrexate, prednisone, and anti–tumor necrosis factor (TNF) agents over time, and after adjusting for potential confounding factors such as disease severity, a strong protective effect on mortality was shown for methotrexate (adjusted hazard ratio 0.23) but not for prednisone (adjusted hazard ratio 1.80), said Dr. Mary Chester Wasko.

Combined treatment with methotrexate and prednisone also had a significant protective effect (hazard ratio 0.34).

“Since methotrexate appeared to be strongly protective with respect to survival in these analyses, and because methotrexate and prednisone are often prescribed together in practice, we questioned whether there might be an interaction between the two drugs with respect to survival,” said Dr. Wasko of the University of Pittsburgh.

Indeed, the strength of the association between methotrexate and improved mortality was only modestly reduced when methotrexate was used in combination with prednisone, she added.

Anti-TNF agents were associated with a slightly decreased risk of mortality. Although the result was not statistically significant (adjusted hazard ratio 0.15), follow-up was limited, as the analyses were based on only 10 deaths out of 598 treated patients with only 5 years of follow-up after these drugs were approved. Additional follow-up is needed to strengthen the results.

Dr. Wasko and her colleagues used the Arthritis, Rheumatism, and Aging Medical Information Systems (ARAMIS) database of patients from 10 U.S. rheumatology practices for their study. The median age of the 5,629 participants was 58 years, 75% were female, 90% were white, and follow-up was a median of 4 years and 3 months. A total of 1,027 patients died during 36,612 patient years of observation.

Patients were evaluated biannually from 1981 to 2003 using the Health Assessment Questionnaire (HAQ).

They reported on demographics, health status (including comorbidities), and medication use.

The outcome of interest was all-cause mortality as confirmed by next of kin.

Major Finding: After taking into consideration the propensity for prescribing methotrexate, prednisone, and anti–tumor necrosis factor agents over time, and after adjusting for potential confounding factors such as disease severity, a strong protective effect on mortality in RA patients was shown for methotrexate (adjusted hazard ratio 0.23) but not for prednisone (adjusted hazard ratio 1.80).

Data Source: An analysis of data – using a novel propensity scoring method – from a longitudinal multicenter observational database of 5,629 RA patients.

Disclosures: Dr. Wasko disclosed that she has received research grants from Amgen, has served as the principle investigator for clinical trials for Centocor, and has served as a consultant for Centocor and UCB.

ATLANTA — Methotrexate use is strongly associated with longer survival in rheumatoid arthritis patients.

After taking into consideration the propensity for prescribing methotrexate, prednisone, and anti–tumor necrosis factor (TNF) agents over time, and after adjusting for potential confounding factors such as disease severity, a strong protective effect on mortality was shown for methotrexate (adjusted hazard ratio 0.23) but not for prednisone (adjusted hazard ratio 1.80), said Dr. Mary Chester Wasko.

Combined treatment with methotrexate and prednisone also had a significant protective effect (hazard ratio 0.34).

“Since methotrexate appeared to be strongly protective with respect to survival in these analyses, and because methotrexate and prednisone are often prescribed together in practice, we questioned whether there might be an interaction between the two drugs with respect to survival,” said Dr. Wasko of the University of Pittsburgh.

Indeed, the strength of the association between methotrexate and improved mortality was only modestly reduced when methotrexate was used in combination with prednisone, she added.

Anti-TNF agents were associated with a slightly decreased risk of mortality. Although the result was not statistically significant (adjusted hazard ratio 0.15), follow-up was limited, as the analyses were based on only 10 deaths out of 598 treated patients with only 5 years of follow-up after these drugs were approved. Additional follow-up is needed to strengthen the results.

Dr. Wasko and her colleagues used the Arthritis, Rheumatism, and Aging Medical Information Systems (ARAMIS) database of patients from 10 U.S. rheumatology practices for their study. The median age of the 5,629 participants was 58 years, 75% were female, 90% were white, and follow-up was a median of 4 years and 3 months. A total of 1,027 patients died during 36,612 patient years of observation.

Patients were evaluated biannually from 1981 to 2003 using the Health Assessment Questionnaire (HAQ).

They reported on demographics, health status (including comorbidities), and medication use.

The outcome of interest was all-cause mortality as confirmed by next of kin.