Sharon Worcester

ATLANTA – Nonbiologic disease-modifying anti-rheumatic drugs – particularly methotrexate – and treat-to-target strategies are at least as responsible as are biologic agents for improvements in the control of rheumatoid arthritis over the last 2 decades.

Data from 1989 to 2008 for 992 patients from the Nijmegen Inception Cohort of patients with newly diagnosed RA showed that the use of biologics increased from 0% around 2000 to 22%, Dr. Wietske Kievit reported at the annual meeting of the American College of Rheumatology.

During the same time period, the use of sulfasalazine decreased from 60% to 16%, with the greatest decline beginning around 2000. Also, the use of methotrexate increased from about 5% to 62%, with the sharpest increases occurring before the biologic era.

"We also saw an increase in the mean dose of methotrexate in the population; in 1989, the mean dose was almost 7 [mg/week] with a maximum of 7.5, and in 2008, the mean dose was 16 with a maximum dose of 30," said Dr. Kievit of Radboud University Nijmegen Medical Centre, the Netherlands.

Estimated mean Disease Activity Scores in 28 joints (DAS28) decreased from 4.3 to 3.2 from 1989 to 2008. The decline in estimated scores was fairly steady over time, and began before the start of the biologic era. A similar trend was seen with functional disability scores, which started at 0.65, and ended at 0.5, with the decreases beginning before the start of the biologic era.

Mean joint damage (Ratingen) scores decreased from 90% in 1989 to 50% in 2005, the last year that data were available for this measure, Dr. Kievit noted. Mean joint damage scores were much lower in the more recent years of follow-up.

She and her colleagues also looked at the number of orthopedic surgeries in the cohort over time. There were 13 surgeries in 197 patients in 1991 (incidence rate 0.07) and 14 in 728 patients in 2008 (incidence rate 0.02).

Patients in the cohort were from two centers in the Netherlands. Patients with newly diagnosed RA were entered into the cohort each year, for a total of 992 patients representing 8419 patient years of follow-up.

Rheumatoid factor and gender did not differ by year, and mean age increased from 56 years in 1989 to 61 years in 2008. Mean disease duration increased from 1.9 to 8.1 years across the study period.

Outcomes were compared by cohort year, and data were adjusted for differences in patient characteristics.

While secular trends, improvements in lifestyle (such as quitting tobacco use), or earlier referrals for specialty care later in the study period could provide an explanation for the improvements in RA control over time, the "most straightforward explanation is the introduction of biologics and tight control strategies, but also enhanced use of methotrexate and other DMARDs already available since the 1980s," Dr. Kievit said.

Neither Dr. Kievit nor any of her coauthors had any financial disclosures related to the presentation of these findings.

ATLANTA – Nonbiologic disease-modifying anti-rheumatic drugs – particularly methotrexate – and treat-to-target strategies are at least as responsible as are biologic agents for improvements in the control of rheumatoid arthritis over the last 2 decades.

Data from 1989 to 2008 for 992 patients from the Nijmegen Inception Cohort of patients with newly diagnosed RA showed that the use of biologics increased from 0% around 2000 to 22%, Dr. Wietske Kievit reported at the annual meeting of the American College of Rheumatology.

During the same time period, the use of sulfasalazine decreased from 60% to 16%, with the greatest decline beginning around 2000. Also, the use of methotrexate increased from about 5% to 62%, with the sharpest increases occurring before the biologic era.

"We also saw an increase in the mean dose of methotrexate in the population; in 1989, the mean dose was almost 7 [mg/week] with a maximum of 7.5, and in 2008, the mean dose was 16 with a maximum dose of 30," said Dr. Kievit of Radboud University Nijmegen Medical Centre, the Netherlands.

Estimated mean Disease Activity Scores in 28 joints (DAS28) decreased from 4.3 to 3.2 from 1989 to 2008. The decline in estimated scores was fairly steady over time, and began before the start of the biologic era. A similar trend was seen with functional disability scores, which started at 0.65, and ended at 0.5, with the decreases beginning before the start of the biologic era.

Mean joint damage (Ratingen) scores decreased from 90% in 1989 to 50% in 2005, the last year that data were available for this measure, Dr. Kievit noted. Mean joint damage scores were much lower in the more recent years of follow-up.

She and her colleagues also looked at the number of orthopedic surgeries in the cohort over time. There were 13 surgeries in 197 patients in 1991 (incidence rate 0.07) and 14 in 728 patients in 2008 (incidence rate 0.02).

Patients in the cohort were from two centers in the Netherlands. Patients with newly diagnosed RA were entered into the cohort each year, for a total of 992 patients representing 8419 patient years of follow-up.

Rheumatoid factor and gender did not differ by year, and mean age increased from 56 years in 1989 to 61 years in 2008. Mean disease duration increased from 1.9 to 8.1 years across the study period.

Outcomes were compared by cohort year, and data were adjusted for differences in patient characteristics.

While secular trends, improvements in lifestyle (such as quitting tobacco use), or earlier referrals for specialty care later in the study period could provide an explanation for the improvements in RA control over time, the "most straightforward explanation is the introduction of biologics and tight control strategies, but also enhanced use of methotrexate and other DMARDs already available since the 1980s," Dr. Kievit said.

Neither Dr. Kievit nor any of her coauthors had any financial disclosures related to the presentation of these findings.

ATLANTA – Nonbiologic disease-modifying anti-rheumatic drugs – particularly methotrexate – and treat-to-target strategies are at least as responsible as are biologic agents for improvements in the control of rheumatoid arthritis over the last 2 decades.

Data from 1989 to 2008 for 992 patients from the Nijmegen Inception Cohort of patients with newly diagnosed RA showed that the use of biologics increased from 0% around 2000 to 22%, Dr. Wietske Kievit reported at the annual meeting of the American College of Rheumatology.

During the same time period, the use of sulfasalazine decreased from 60% to 16%, with the greatest decline beginning around 2000. Also, the use of methotrexate increased from about 5% to 62%, with the sharpest increases occurring before the biologic era.

"We also saw an increase in the mean dose of methotrexate in the population; in 1989, the mean dose was almost 7 [mg/week] with a maximum of 7.5, and in 2008, the mean dose was 16 with a maximum dose of 30," said Dr. Kievit of Radboud University Nijmegen Medical Centre, the Netherlands.

Estimated mean Disease Activity Scores in 28 joints (DAS28) decreased from 4.3 to 3.2 from 1989 to 2008. The decline in estimated scores was fairly steady over time, and began before the start of the biologic era. A similar trend was seen with functional disability scores, which started at 0.65, and ended at 0.5, with the decreases beginning before the start of the biologic era.

Mean joint damage (Ratingen) scores decreased from 90% in 1989 to 50% in 2005, the last year that data were available for this measure, Dr. Kievit noted. Mean joint damage scores were much lower in the more recent years of follow-up.

She and her colleagues also looked at the number of orthopedic surgeries in the cohort over time. There were 13 surgeries in 197 patients in 1991 (incidence rate 0.07) and 14 in 728 patients in 2008 (incidence rate 0.02).

Patients in the cohort were from two centers in the Netherlands. Patients with newly diagnosed RA were entered into the cohort each year, for a total of 992 patients representing 8419 patient years of follow-up.

Rheumatoid factor and gender did not differ by year, and mean age increased from 56 years in 1989 to 61 years in 2008. Mean disease duration increased from 1.9 to 8.1 years across the study period.

Outcomes were compared by cohort year, and data were adjusted for differences in patient characteristics.

While secular trends, improvements in lifestyle (such as quitting tobacco use), or earlier referrals for specialty care later in the study period could provide an explanation for the improvements in RA control over time, the "most straightforward explanation is the introduction of biologics and tight control strategies, but also enhanced use of methotrexate and other DMARDs already available since the 1980s," Dr. Kievit said.

Neither Dr. Kievit nor any of her coauthors had any financial disclosures related to the presentation of these findings.

Patients with type 2 diabetes were more likely to have genetic variations for a key protein regulating cells' insulin receptors, according to a multinational case-control study.

The variants' presence could serve as an early predictive marker of insulin resistance and type 2 diabetes, particularly in patients with a family history of the disease, the study's authors noted.

The investigators examined variations in the high-mobility group A1 protein, or HMGA1, a key regulator of insulin receptor gene expression. The protein's most frequent functional variant was found in 7.2% of the study's 3,278 Italian patients with type 2 diabetes, compared with 0.4% and 3.3% of two Italian control groups (2,544 and 784 patients) without diabetes, significant differences resulting in adjusted odds ratios of 15.8 and 2.0, respectively.

In addition, the variant was found in 7.7% of 970 U.S. case patients, compared with 4.7% of 958 U.S. control patients (adjusted odds ratio, 1.6), a significant difference, and in 7.6% of 354 French case patients vs. 0% of 50 French controls, also a significant difference, reported Dr. Eusebio Chiefari of the University of Catanzaro (Italy) and colleagues (JAMA 2011;305:903-12).

Three other functional variants also were observed in the Italian population, although those variants were not studied in the U.S. and French populations because of the relatively small sample sizes.

Overall, when all four variants were analyzed, nearly 10% of Italian patients with type 2 diabetes were found to have HMGA1 defects, compared with less than 1% of controls.

The four variants of the HMGA1 gene were also shown to be associated with decreased insulin receptor gene and insulin receptor protein expression.

The authors reported no disclosures. Telethon-Italy, MIUR Italy, and the U.S. National Institutes of Health providing funding for the study.

Patients with type 2 diabetes were more likely to have genetic variations for a key protein regulating cells' insulin receptors, according to a multinational case-control study.

The variants' presence could serve as an early predictive marker of insulin resistance and type 2 diabetes, particularly in patients with a family history of the disease, the study's authors noted.

The investigators examined variations in the high-mobility group A1 protein, or HMGA1, a key regulator of insulin receptor gene expression. The protein's most frequent functional variant was found in 7.2% of the study's 3,278 Italian patients with type 2 diabetes, compared with 0.4% and 3.3% of two Italian control groups (2,544 and 784 patients) without diabetes, significant differences resulting in adjusted odds ratios of 15.8 and 2.0, respectively.

In addition, the variant was found in 7.7% of 970 U.S. case patients, compared with 4.7% of 958 U.S. control patients (adjusted odds ratio, 1.6), a significant difference, and in 7.6% of 354 French case patients vs. 0% of 50 French controls, also a significant difference, reported Dr. Eusebio Chiefari of the University of Catanzaro (Italy) and colleagues (JAMA 2011;305:903-12).

Three other functional variants also were observed in the Italian population, although those variants were not studied in the U.S. and French populations because of the relatively small sample sizes.

Overall, when all four variants were analyzed, nearly 10% of Italian patients with type 2 diabetes were found to have HMGA1 defects, compared with less than 1% of controls.

The four variants of the HMGA1 gene were also shown to be associated with decreased insulin receptor gene and insulin receptor protein expression.

The authors reported no disclosures. Telethon-Italy, MIUR Italy, and the U.S. National Institutes of Health providing funding for the study.

Patients with type 2 diabetes were more likely to have genetic variations for a key protein regulating cells' insulin receptors, according to a multinational case-control study.

The variants' presence could serve as an early predictive marker of insulin resistance and type 2 diabetes, particularly in patients with a family history of the disease, the study's authors noted.

The investigators examined variations in the high-mobility group A1 protein, or HMGA1, a key regulator of insulin receptor gene expression. The protein's most frequent functional variant was found in 7.2% of the study's 3,278 Italian patients with type 2 diabetes, compared with 0.4% and 3.3% of two Italian control groups (2,544 and 784 patients) without diabetes, significant differences resulting in adjusted odds ratios of 15.8 and 2.0, respectively.

In addition, the variant was found in 7.7% of 970 U.S. case patients, compared with 4.7% of 958 U.S. control patients (adjusted odds ratio, 1.6), a significant difference, and in 7.6% of 354 French case patients vs. 0% of 50 French controls, also a significant difference, reported Dr. Eusebio Chiefari of the University of Catanzaro (Italy) and colleagues (JAMA 2011;305:903-12).

Three other functional variants also were observed in the Italian population, although those variants were not studied in the U.S. and French populations because of the relatively small sample sizes.

Overall, when all four variants were analyzed, nearly 10% of Italian patients with type 2 diabetes were found to have HMGA1 defects, compared with less than 1% of controls.

The four variants of the HMGA1 gene were also shown to be associated with decreased insulin receptor gene and insulin receptor protein expression.

The authors reported no disclosures. Telethon-Italy, MIUR Italy, and the U.S. National Institutes of Health providing funding for the study.

Major Finding: A 2- to 6-hour delay in suture placement was found to be independently associated with a fourfold increase in the odds of hysterectomy.

Data Source: A prospective population-based study of 1.2 million women, 210 of whom were treated with a uterine compression suture to control postpartum hemorrhage.

Disclosures: 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 study author, 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.

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, they 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.

View on The News

Technique Often Useful

Dr. Carolyn Zelop said that this study has important implications for practice. “I think the take-home message … is that [the use of compression sutures] is a very reliable technique, but that it's probably less useful in the setting of placenta accreta,” explaining that uterine atony appears to be the indication that leads to the most success with this technique.

Another important point made by the authors is that in the setting of vaginal delivery that is complicated by postpartum hemorrhage, it is important to “be on the clock and ready to move to the next intervention,” since a delay of 2–6 hours in suture placement was associated with increased risk of hysterectomy.

Although it seems logical that a clinician might be reluctant to proceed with laparotomy after vaginal delivery, a prolonged delay could predispose a patient to unrecognized blood loss, and increase the risk of compression suture failure. If mechanical tamponade techniques fail to control hemorrhaging, the clinician should proceed with laparotomy and uterine compression suture placement, she advised.

Vitals

DR. ZELOP is director of maternal-fetal medicine at Beth Israel Deaconess Medical Center in Boston. She said she had no relevant financial disclosures.

Major Finding: A 2- to 6-hour delay in suture placement was found to be independently associated with a fourfold increase in the odds of hysterectomy.

Data Source: A prospective population-based study of 1.2 million women, 210 of whom were treated with a uterine compression suture to control postpartum hemorrhage.

Disclosures: 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 study author, 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.

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, they 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.

View on The News

Technique Often Useful

Dr. Carolyn Zelop said that this study has important implications for practice. “I think the take-home message … is that [the use of compression sutures] is a very reliable technique, but that it's probably less useful in the setting of placenta accreta,” explaining that uterine atony appears to be the indication that leads to the most success with this technique.

Another important point made by the authors is that in the setting of vaginal delivery that is complicated by postpartum hemorrhage, it is important to “be on the clock and ready to move to the next intervention,” since a delay of 2–6 hours in suture placement was associated with increased risk of hysterectomy.

Although it seems logical that a clinician might be reluctant to proceed with laparotomy after vaginal delivery, a prolonged delay could predispose a patient to unrecognized blood loss, and increase the risk of compression suture failure. If mechanical tamponade techniques fail to control hemorrhaging, the clinician should proceed with laparotomy and uterine compression suture placement, she advised.

Vitals

DR. ZELOP is director of maternal-fetal medicine at Beth Israel Deaconess Medical Center in Boston. She said she had no relevant financial disclosures.

Major Finding: A 2- to 6-hour delay in suture placement was found to be independently associated with a fourfold increase in the odds of hysterectomy.

Data Source: A prospective population-based study of 1.2 million women, 210 of whom were treated with a uterine compression suture to control postpartum hemorrhage.

Disclosures: 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 study author, 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.

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, they 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.

View on The News

Technique Often Useful

Dr. Carolyn Zelop said that this study has important implications for practice. “I think the take-home message … is that [the use of compression sutures] is a very reliable technique, but that it's probably less useful in the setting of placenta accreta,” explaining that uterine atony appears to be the indication that leads to the most success with this technique.

Another important point made by the authors is that in the setting of vaginal delivery that is complicated by postpartum hemorrhage, it is important to “be on the clock and ready to move to the next intervention,” since a delay of 2–6 hours in suture placement was associated with increased risk of hysterectomy.

Although it seems logical that a clinician might be reluctant to proceed with laparotomy after vaginal delivery, a prolonged delay could predispose a patient to unrecognized blood loss, and increase the risk of compression suture failure. If mechanical tamponade techniques fail to control hemorrhaging, the clinician should proceed with laparotomy and uterine compression suture placement, she advised.

Vitals

DR. ZELOP is director of maternal-fetal medicine at Beth Israel Deaconess Medical Center in Boston. She said she had no relevant financial disclosures.

Major Finding: Of 325 children enrolled in the Research Registry for Neonatal Lupus before October 2010, 57 (18%) died; 30% died in utero, 30% died during the neonatal period, 14% died between 1 and 6 months of age, and 26% died after 6 months of age.

Data Source: A retrospective analysis of data from a large U.S.-based cohort.

Disclosures: Dr. Izmirly had no disclosures.

ATLANTA — The overall case fatality rate in cardiac neonatal lupus is nearly 18%, according to a review of data from the Research Registry for Neonatal Lupus.

Of 325 children enrolled in the large U.S.-based registry before October 2010, 57 (18%) died; 30% died in utero, 30% died during the neonatal period, 14% died between 1 and 6 months of age, and 26% died after 6 months of age, Dr. Peter M. Izmirly reported at the meeting.

Of the deaths, 42 were cardiac related – most often a result of complications from cardiomyopathy, 6 were due to infectious complications, and 8 were a result of unknown causes. One pregnancy was terminated electively, said Dr. Izmirly of New York University, New York.

“There was a significantly higher case fatality rate in minorities, compared with Caucasians,” Dr. Izmirly said, noting that 14% of white children with cardiac neonatal lupus died, compared with 28% of children belonging to minority groups.

The study, which was conducted in an effort to update morality data on cardiac neonatal lupus and to thereby improve evidence-based counseling of anti-Ro/La positive mothers whose babies are at increased risk of cardiac neonatal lupus, identified fetal and maternal risk factors for death in affected babies.

Significant fetal risk factors for death were associated hematologic hepatic neonatal lupus (present in 27% vs. 7% of deceased vs. living babies), earlier gestational age at detection (detection occurred at 21.8 vs. 23.4 weeks in deceased vs. living babies), delivery prior to 37 weeks' gestation (delivery occurred prior to 37 weeks in 69% vs. 42% of deceased vs. living babies), and earlier gestational week of delivery (delivery occurred at 34.2 weeks vs. 36.9 weeks in deceased vs. living babies), Dr. Izmirly said.

Fetal risk factors not found to be associated with mortality were female sex, associated neonatal lupus rash, cesarean section delivery, and year of birth.

Fetal echocardiographic risk factors associated with mortality were lower ventricular rate nadir (rate was 50.2 vs. 53.6 in deceased vs. living babies), and the presence of endocardial fibroelastosis (which occurred in 30.25% vs. 4.3% of deceased vs. living babies), dilated cardiomyopathy (which occurred in 32.6% vs. 8.6% of deceased vs. living babies), hydrops (which occurred in 57.4% vs. 3.4% of deceased vs. living babies), and valvular disease (which occurred in 18.2% vs. 4.8% of deceased vs. living babies).

Fetal echocardiographic factors not associated with mortality were ventricular rate detection, atrial septal defect, ventricular septal defect, and patent ductus arteriosus.

Only one maternal risk factor – a maternal diagnosis of systemic lupus erythematosus or Sjögren's syndrome – showed a trend toward significance in terms of risk for fetal death. Diagnosis occurred in 56% of women whose babies died, vs. 43% of those whose babies were living.

Maternal age, maternal anti-La antibodies, maternal anti–52-kD Ro antibodies, and use of nonfluorinated steroids, fluorinated steroids, terbutaline, or hydroxychloroquine were not associated with increased risk of fetal mortality.

As for morbidity in affected children, 70% required pacing – including 1% in utero, 53% in the neonatal period, 12% between ages 1 and 6 months, and 32% after age 6 months. The timing was unknown in 3% of cases.

Also, four children required cardiac transplantation, including one child who required two transplants, Dr. Izmirly said.

“Cardiac neonatal lupus is associated with substantial mortality, which is predicted by slower heart rates and echocardiographic abnormalities consistent with antibody-associated disease beyond the AV node,” Dr. Izmirly concluded, adding that the disparity in outcomes between whites and minorities suggests that attention should be given to “an inherent difference in organ response to injury, and/or access to care.”

Major Finding: Of 325 children enrolled in the Research Registry for Neonatal Lupus before October 2010, 57 (18%) died; 30% died in utero, 30% died during the neonatal period, 14% died between 1 and 6 months of age, and 26% died after 6 months of age.

Data Source: A retrospective analysis of data from a large U.S.-based cohort.

Disclosures: Dr. Izmirly had no disclosures.

ATLANTA — The overall case fatality rate in cardiac neonatal lupus is nearly 18%, according to a review of data from the Research Registry for Neonatal Lupus.

Of 325 children enrolled in the large U.S.-based registry before October 2010, 57 (18%) died; 30% died in utero, 30% died during the neonatal period, 14% died between 1 and 6 months of age, and 26% died after 6 months of age, Dr. Peter M. Izmirly reported at the meeting.

Of the deaths, 42 were cardiac related – most often a result of complications from cardiomyopathy, 6 were due to infectious complications, and 8 were a result of unknown causes. One pregnancy was terminated electively, said Dr. Izmirly of New York University, New York.

“There was a significantly higher case fatality rate in minorities, compared with Caucasians,” Dr. Izmirly said, noting that 14% of white children with cardiac neonatal lupus died, compared with 28% of children belonging to minority groups.

The study, which was conducted in an effort to update morality data on cardiac neonatal lupus and to thereby improve evidence-based counseling of anti-Ro/La positive mothers whose babies are at increased risk of cardiac neonatal lupus, identified fetal and maternal risk factors for death in affected babies.

Significant fetal risk factors for death were associated hematologic hepatic neonatal lupus (present in 27% vs. 7% of deceased vs. living babies), earlier gestational age at detection (detection occurred at 21.8 vs. 23.4 weeks in deceased vs. living babies), delivery prior to 37 weeks' gestation (delivery occurred prior to 37 weeks in 69% vs. 42% of deceased vs. living babies), and earlier gestational week of delivery (delivery occurred at 34.2 weeks vs. 36.9 weeks in deceased vs. living babies), Dr. Izmirly said.

Fetal risk factors not found to be associated with mortality were female sex, associated neonatal lupus rash, cesarean section delivery, and year of birth.

Fetal echocardiographic risk factors associated with mortality were lower ventricular rate nadir (rate was 50.2 vs. 53.6 in deceased vs. living babies), and the presence of endocardial fibroelastosis (which occurred in 30.25% vs. 4.3% of deceased vs. living babies), dilated cardiomyopathy (which occurred in 32.6% vs. 8.6% of deceased vs. living babies), hydrops (which occurred in 57.4% vs. 3.4% of deceased vs. living babies), and valvular disease (which occurred in 18.2% vs. 4.8% of deceased vs. living babies).

Fetal echocardiographic factors not associated with mortality were ventricular rate detection, atrial septal defect, ventricular septal defect, and patent ductus arteriosus.

Only one maternal risk factor – a maternal diagnosis of systemic lupus erythematosus or Sjögren's syndrome – showed a trend toward significance in terms of risk for fetal death. Diagnosis occurred in 56% of women whose babies died, vs. 43% of those whose babies were living.

Maternal age, maternal anti-La antibodies, maternal anti–52-kD Ro antibodies, and use of nonfluorinated steroids, fluorinated steroids, terbutaline, or hydroxychloroquine were not associated with increased risk of fetal mortality.

As for morbidity in affected children, 70% required pacing – including 1% in utero, 53% in the neonatal period, 12% between ages 1 and 6 months, and 32% after age 6 months. The timing was unknown in 3% of cases.

Also, four children required cardiac transplantation, including one child who required two transplants, Dr. Izmirly said.

“Cardiac neonatal lupus is associated with substantial mortality, which is predicted by slower heart rates and echocardiographic abnormalities consistent with antibody-associated disease beyond the AV node,” Dr. Izmirly concluded, adding that the disparity in outcomes between whites and minorities suggests that attention should be given to “an inherent difference in organ response to injury, and/or access to care.”

Major Finding: Of 325 children enrolled in the Research Registry for Neonatal Lupus before October 2010, 57 (18%) died; 30% died in utero, 30% died during the neonatal period, 14% died between 1 and 6 months of age, and 26% died after 6 months of age.

Data Source: A retrospective analysis of data from a large U.S.-based cohort.

Disclosures: Dr. Izmirly had no disclosures.

ATLANTA — The overall case fatality rate in cardiac neonatal lupus is nearly 18%, according to a review of data from the Research Registry for Neonatal Lupus.

Of 325 children enrolled in the large U.S.-based registry before October 2010, 57 (18%) died; 30% died in utero, 30% died during the neonatal period, 14% died between 1 and 6 months of age, and 26% died after 6 months of age, Dr. Peter M. Izmirly reported at the meeting.

Of the deaths, 42 were cardiac related – most often a result of complications from cardiomyopathy, 6 were due to infectious complications, and 8 were a result of unknown causes. One pregnancy was terminated electively, said Dr. Izmirly of New York University, New York.

“There was a significantly higher case fatality rate in minorities, compared with Caucasians,” Dr. Izmirly said, noting that 14% of white children with cardiac neonatal lupus died, compared with 28% of children belonging to minority groups.

The study, which was conducted in an effort to update morality data on cardiac neonatal lupus and to thereby improve evidence-based counseling of anti-Ro/La positive mothers whose babies are at increased risk of cardiac neonatal lupus, identified fetal and maternal risk factors for death in affected babies.

Significant fetal risk factors for death were associated hematologic hepatic neonatal lupus (present in 27% vs. 7% of deceased vs. living babies), earlier gestational age at detection (detection occurred at 21.8 vs. 23.4 weeks in deceased vs. living babies), delivery prior to 37 weeks' gestation (delivery occurred prior to 37 weeks in 69% vs. 42% of deceased vs. living babies), and earlier gestational week of delivery (delivery occurred at 34.2 weeks vs. 36.9 weeks in deceased vs. living babies), Dr. Izmirly said.

Fetal risk factors not found to be associated with mortality were female sex, associated neonatal lupus rash, cesarean section delivery, and year of birth.

Fetal echocardiographic risk factors associated with mortality were lower ventricular rate nadir (rate was 50.2 vs. 53.6 in deceased vs. living babies), and the presence of endocardial fibroelastosis (which occurred in 30.25% vs. 4.3% of deceased vs. living babies), dilated cardiomyopathy (which occurred in 32.6% vs. 8.6% of deceased vs. living babies), hydrops (which occurred in 57.4% vs. 3.4% of deceased vs. living babies), and valvular disease (which occurred in 18.2% vs. 4.8% of deceased vs. living babies).

Fetal echocardiographic factors not associated with mortality were ventricular rate detection, atrial septal defect, ventricular septal defect, and patent ductus arteriosus.

Only one maternal risk factor – a maternal diagnosis of systemic lupus erythematosus or Sjögren's syndrome – showed a trend toward significance in terms of risk for fetal death. Diagnosis occurred in 56% of women whose babies died, vs. 43% of those whose babies were living.

Maternal age, maternal anti-La antibodies, maternal anti–52-kD Ro antibodies, and use of nonfluorinated steroids, fluorinated steroids, terbutaline, or hydroxychloroquine were not associated with increased risk of fetal mortality.

As for morbidity in affected children, 70% required pacing – including 1% in utero, 53% in the neonatal period, 12% between ages 1 and 6 months, and 32% after age 6 months. The timing was unknown in 3% of cases.

Also, four children required cardiac transplantation, including one child who required two transplants, Dr. Izmirly said.

“Cardiac neonatal lupus is associated with substantial mortality, which is predicted by slower heart rates and echocardiographic abnormalities consistent with antibody-associated disease beyond the AV node,” Dr. Izmirly concluded, adding that the disparity in outcomes between whites and minorities suggests that attention should be given to “an inherent difference in organ response to injury, and/or access to care.”

Major Finding: Independent predictors of vaccine series completion were white (vs. black) race (odds ratio, 2.04 at 7 months; 1.92, at 12 months); use of contraception that required IM injection every 3 months (OR, 1.53 at 7 months; 2.06 at 12 months); and private vs. public insurance (OR, 1.31 at 7 months; 1.16 at 12 months).

Data Source: A retrospective study of health information records for 3,297 female patients (aged 9–26 years) who initiated HPV vaccination at a pediatric academic medical center.

Disclosures: Dr. Widdice said she has received research support through the investigator-initiated studies program of Merck & Co. for research unrelated to this study. Another author on the study, Dr. Jessica A. Kahn, is a co–principal investigator of a National Institutes of Health–funded clinical trial of HPV vaccine in HIV-infected adolescents, for which Merck is providing HPV vaccine and immunogenicity testing. The other investigators said they had no relevant financial disclosures. This study was funded by the NIH.

More than half of the doses of human papillomavirus vaccine received by 3,297 girls and young women undergoing vaccination at an academic medical center were received late, and the three-dose vaccine series completion rate was only 14% by 7 months and 28% by 12 months, according to a retrospective medical records study.

Adherence to the recommended interval of 2 months between the first and second dose was 28.5%, and adherence to the recommended intervals of 12 weeks between the second and third dose, and 6 months between the first and third dose was only 19.7% and 13.3%. Adherence to all three intervals was just 11.5%, Dr. Lea E. Widdice of Cincinnati Children's Research Foundation and her colleagues reported (Pediatrics 2011;127:77-84)

The average time between dose one and two was about 6 months, and the average time between dose one and three was 11 months, the investigators noted.

Independent predictors of vaccine series completion were white (vs. black) race (odds ratio, 2.04 at 7 months; 1.92 at 12 months); use of contraception that required intramuscular injection every 3 months (OR, 1.53 at 7 months; 2.06 at 12 months); and private (vs. public) insurance (OR, 1.31 at 7 months; 1.16 at 12 months), they found. Age did not predict adherence.

The investigators reviewed the health information records of all 9- to 26-year-old girls and women who initiated vaccination at Cincinnati Children's Hospital Medical Center from November 2006 to June 2008.

“Understanding adherence to the HPV4 recommended vaccination schedule, and identifying factors that predict completion among adolescents who initiate vaccination are necessary to develop evidence-based strategies to increase adherence among adolescents,” Dr. Widdice and her associates wrote.

The findings are of concern because although the vaccine has been shown in clinical trials to be 94%–100% effective, the duration of protection and efficacy in those who don't complete the vaccine series or who receive doses at intervals different from those in the clinical trials are currently unknown, and because the decreased likelihood of series completion among black subjects – who comprised about two-thirds of the study subjects – could exacerbate existing disparities in cervical cancer, the investigators said.

“In future studies, factors that underlie the association between race and completion of the HPV4 series should be examined,” they wrote, adding that the health care community should be vigilant in providing education and access to all patients.

Future studies also should compare immunization status for HPV and other diseases in adolescents, should aim to understand rates of and reason for not initiating vaccination in an effort to optimize HPV4 vaccine coverage, and should assess factors related to HPV vaccine adherence in male patients now that there is a “permissive recommendation” for use in that population and since factors could differ between male and female patients, they said.

In this study, compared with HPV4 vaccine clinical trials, the mean completion rates were lower, and the mean intervals between doses were longer.

“Clinical improvement efforts should focus on timing of the second dose as well as completion of three doses,” Dr. Widdice and her associates added.

Major Finding: Independent predictors of vaccine series completion were white (vs. black) race (odds ratio, 2.04 at 7 months; 1.92, at 12 months); use of contraception that required IM injection every 3 months (OR, 1.53 at 7 months; 2.06 at 12 months); and private vs. public insurance (OR, 1.31 at 7 months; 1.16 at 12 months).

Data Source: A retrospective study of health information records for 3,297 female patients (aged 9–26 years) who initiated HPV vaccination at a pediatric academic medical center.

Disclosures: Dr. Widdice said she has received research support through the investigator-initiated studies program of Merck & Co. for research unrelated to this study. Another author on the study, Dr. Jessica A. Kahn, is a co–principal investigator of a National Institutes of Health–funded clinical trial of HPV vaccine in HIV-infected adolescents, for which Merck is providing HPV vaccine and immunogenicity testing. The other investigators said they had no relevant financial disclosures. This study was funded by the NIH.

More than half of the doses of human papillomavirus vaccine received by 3,297 girls and young women undergoing vaccination at an academic medical center were received late, and the three-dose vaccine series completion rate was only 14% by 7 months and 28% by 12 months, according to a retrospective medical records study.

Adherence to the recommended interval of 2 months between the first and second dose was 28.5%, and adherence to the recommended intervals of 12 weeks between the second and third dose, and 6 months between the first and third dose was only 19.7% and 13.3%. Adherence to all three intervals was just 11.5%, Dr. Lea E. Widdice of Cincinnati Children's Research Foundation and her colleagues reported (Pediatrics 2011;127:77-84)

The average time between dose one and two was about 6 months, and the average time between dose one and three was 11 months, the investigators noted.

Independent predictors of vaccine series completion were white (vs. black) race (odds ratio, 2.04 at 7 months; 1.92 at 12 months); use of contraception that required intramuscular injection every 3 months (OR, 1.53 at 7 months; 2.06 at 12 months); and private (vs. public) insurance (OR, 1.31 at 7 months; 1.16 at 12 months), they found. Age did not predict adherence.

The investigators reviewed the health information records of all 9- to 26-year-old girls and women who initiated vaccination at Cincinnati Children's Hospital Medical Center from November 2006 to June 2008.

“Understanding adherence to the HPV4 recommended vaccination schedule, and identifying factors that predict completion among adolescents who initiate vaccination are necessary to develop evidence-based strategies to increase adherence among adolescents,” Dr. Widdice and her associates wrote.

The findings are of concern because although the vaccine has been shown in clinical trials to be 94%–100% effective, the duration of protection and efficacy in those who don't complete the vaccine series or who receive doses at intervals different from those in the clinical trials are currently unknown, and because the decreased likelihood of series completion among black subjects – who comprised about two-thirds of the study subjects – could exacerbate existing disparities in cervical cancer, the investigators said.

“In future studies, factors that underlie the association between race and completion of the HPV4 series should be examined,” they wrote, adding that the health care community should be vigilant in providing education and access to all patients.

Future studies also should compare immunization status for HPV and other diseases in adolescents, should aim to understand rates of and reason for not initiating vaccination in an effort to optimize HPV4 vaccine coverage, and should assess factors related to HPV vaccine adherence in male patients now that there is a “permissive recommendation” for use in that population and since factors could differ between male and female patients, they said.

In this study, compared with HPV4 vaccine clinical trials, the mean completion rates were lower, and the mean intervals between doses were longer.

“Clinical improvement efforts should focus on timing of the second dose as well as completion of three doses,” Dr. Widdice and her associates added.

Major Finding: Independent predictors of vaccine series completion were white (vs. black) race (odds ratio, 2.04 at 7 months; 1.92, at 12 months); use of contraception that required IM injection every 3 months (OR, 1.53 at 7 months; 2.06 at 12 months); and private vs. public insurance (OR, 1.31 at 7 months; 1.16 at 12 months).

Data Source: A retrospective study of health information records for 3,297 female patients (aged 9–26 years) who initiated HPV vaccination at a pediatric academic medical center.

Disclosures: Dr. Widdice said she has received research support through the investigator-initiated studies program of Merck & Co. for research unrelated to this study. Another author on the study, Dr. Jessica A. Kahn, is a co–principal investigator of a National Institutes of Health–funded clinical trial of HPV vaccine in HIV-infected adolescents, for which Merck is providing HPV vaccine and immunogenicity testing. The other investigators said they had no relevant financial disclosures. This study was funded by the NIH.

More than half of the doses of human papillomavirus vaccine received by 3,297 girls and young women undergoing vaccination at an academic medical center were received late, and the three-dose vaccine series completion rate was only 14% by 7 months and 28% by 12 months, according to a retrospective medical records study.

Adherence to the recommended interval of 2 months between the first and second dose was 28.5%, and adherence to the recommended intervals of 12 weeks between the second and third dose, and 6 months between the first and third dose was only 19.7% and 13.3%. Adherence to all three intervals was just 11.5%, Dr. Lea E. Widdice of Cincinnati Children's Research Foundation and her colleagues reported (Pediatrics 2011;127:77-84)

The average time between dose one and two was about 6 months, and the average time between dose one and three was 11 months, the investigators noted.

Independent predictors of vaccine series completion were white (vs. black) race (odds ratio, 2.04 at 7 months; 1.92 at 12 months); use of contraception that required intramuscular injection every 3 months (OR, 1.53 at 7 months; 2.06 at 12 months); and private (vs. public) insurance (OR, 1.31 at 7 months; 1.16 at 12 months), they found. Age did not predict adherence.

The investigators reviewed the health information records of all 9- to 26-year-old girls and women who initiated vaccination at Cincinnati Children's Hospital Medical Center from November 2006 to June 2008.

“Understanding adherence to the HPV4 recommended vaccination schedule, and identifying factors that predict completion among adolescents who initiate vaccination are necessary to develop evidence-based strategies to increase adherence among adolescents,” Dr. Widdice and her associates wrote.

The findings are of concern because although the vaccine has been shown in clinical trials to be 94%–100% effective, the duration of protection and efficacy in those who don't complete the vaccine series or who receive doses at intervals different from those in the clinical trials are currently unknown, and because the decreased likelihood of series completion among black subjects – who comprised about two-thirds of the study subjects – could exacerbate existing disparities in cervical cancer, the investigators said.

“In future studies, factors that underlie the association between race and completion of the HPV4 series should be examined,” they wrote, adding that the health care community should be vigilant in providing education and access to all patients.

Future studies also should compare immunization status for HPV and other diseases in adolescents, should aim to understand rates of and reason for not initiating vaccination in an effort to optimize HPV4 vaccine coverage, and should assess factors related to HPV vaccine adherence in male patients now that there is a “permissive recommendation” for use in that population and since factors could differ between male and female patients, they said.

In this study, compared with HPV4 vaccine clinical trials, the mean completion rates were lower, and the mean intervals between doses were longer.

“Clinical improvement efforts should focus on timing of the second dose as well as completion of three doses,” Dr. Widdice and her associates added.

One year of adjuvant trastuzumab following standard chemotherapy is associated with significantly improved long-term, disease-free survival in women with early-stage HER2-positive breast cancer, according to updated findings from the ongoing international, randomized phase III Herceptin Adjuvant trial.

Disease-free survival at a median follow-up of 48.4 months was 78.6% in 1,703 women who were initially randomized to receive 1 year of treatment with trastuzumab (Herceptin) following chemotherapy, compared with 72.2% in 1,698 women randomized to observation following chemotherapy (hazard ratio, 0.76), Dr. Luca Gianni of the Istituto Nazioniale dei Tumori in Milan and colleagues from the HERA Trial Study Team reported online in the Feb. 25 issue of the Lancet Oncology.

Overall survival did not differ significantly between the treatment and observation groups (89.3% and 87.7%, respectively), but the investigators attributed this to the substantial crossover from the observation group to the treatment group after 1-year follow-up results from this study, which were published in 2005.

"This effect was not recorded at 2-year median follow-up, probably because of the short duration of follow-up after crossover at that time" (median, 2.6 moths vs. 29.1 months in this analysis)," they explained.

More than half (52%) of the observation group patients crossed over to receive trastuzumab after the 1-year analysis, beginning treatment at a median of 22.8 months after randomization. Those patients were found in the current study to have fewer disease-free survival events than did those who did not cross over (adjusted hazard ratio, 0.68), the investigators said (Lancet Oncol. 2011 Feb. 25 [doi:10.1016/S1470-2045(11)70033-x]).

Women in the HERA trial had early-stage HER-2-positive breast cancer, an aggressive form of breast cancer that represents about 15%-25% of breast cancers and confers an increased risk of recurrence and mortality. They were enrolled between December 2001 and June 2005, and were randomized to an observation group, a 1-year treatment group, or a 2-year treatment group. Treatment group patients received trastuzumab, a humanized monoclonal antibody that targets the extracellular domain of the HER2 receptor. Treatment was given as an intravenous infusion over 90 minutes every 3 weeks at an initial loading dose of 8 mg/kg and at a dose of 6 mg/kg thereafter.

Trastuzumab was generally well tolerated, although higher incidence of grades 3/4 and fatal adverse events occurred in the 1-year treatment group than in the observation group, they noted, adding that the most common of these – cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhea – each occurred in fewer than 1% of patients.

The interim analysis at 1 year showed that 12 months of treatment with trastuzumab was associated with a 46% reduction in disease recurrence. The 2-year follow-up data that were published in 2007 confirmed the disease-free survival benefit (HR, 0.64) and also demonstrated an overall survival benefit (HR, 0.66), the investigators noted.

"The HERA trial results confirm that treatment with adjuvant trastuzumab for 1 year is associated with persisting benefit in women with HER2-positive early breast cancer," the investigators said, concluding that trastuzumab given sequentially to chemotherapy "remains an appropriate treatment modality" in these patients.

They also noted that the possibility that women might derive further benefits from treatment for longer than 1 year is currently being explored in a comparison of the outcomes in the 1-year and 2-year treatment groups of the HERA trial.

F. Hoffmann-La Roche and the Michelangelo Foundation funded the study, which was conducted by the Breast International Group (BIG). Several authors, including Dr. Gianni, reported receiving funding from Roche, such as for advisory board membership, research support, speakers honoraria, consultancy, and travel. One author, Susanne Muehlbauer, is an employee of Roche and has stock options in the company. 

One year of adjuvant trastuzumab following standard chemotherapy is associated with significantly improved long-term, disease-free survival in women with early-stage HER2-positive breast cancer, according to updated findings from the ongoing international, randomized phase III Herceptin Adjuvant trial.

Disease-free survival at a median follow-up of 48.4 months was 78.6% in 1,703 women who were initially randomized to receive 1 year of treatment with trastuzumab (Herceptin) following chemotherapy, compared with 72.2% in 1,698 women randomized to observation following chemotherapy (hazard ratio, 0.76), Dr. Luca Gianni of the Istituto Nazioniale dei Tumori in Milan and colleagues from the HERA Trial Study Team reported online in the Feb. 25 issue of the Lancet Oncology.

Overall survival did not differ significantly between the treatment and observation groups (89.3% and 87.7%, respectively), but the investigators attributed this to the substantial crossover from the observation group to the treatment group after 1-year follow-up results from this study, which were published in 2005.

"This effect was not recorded at 2-year median follow-up, probably because of the short duration of follow-up after crossover at that time" (median, 2.6 moths vs. 29.1 months in this analysis)," they explained.

More than half (52%) of the observation group patients crossed over to receive trastuzumab after the 1-year analysis, beginning treatment at a median of 22.8 months after randomization. Those patients were found in the current study to have fewer disease-free survival events than did those who did not cross over (adjusted hazard ratio, 0.68), the investigators said (Lancet Oncol. 2011 Feb. 25 [doi:10.1016/S1470-2045(11)70033-x]).

Women in the HERA trial had early-stage HER-2-positive breast cancer, an aggressive form of breast cancer that represents about 15%-25% of breast cancers and confers an increased risk of recurrence and mortality. They were enrolled between December 2001 and June 2005, and were randomized to an observation group, a 1-year treatment group, or a 2-year treatment group. Treatment group patients received trastuzumab, a humanized monoclonal antibody that targets the extracellular domain of the HER2 receptor. Treatment was given as an intravenous infusion over 90 minutes every 3 weeks at an initial loading dose of 8 mg/kg and at a dose of 6 mg/kg thereafter.

Trastuzumab was generally well tolerated, although higher incidence of grades 3/4 and fatal adverse events occurred in the 1-year treatment group than in the observation group, they noted, adding that the most common of these – cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhea – each occurred in fewer than 1% of patients.

The interim analysis at 1 year showed that 12 months of treatment with trastuzumab was associated with a 46% reduction in disease recurrence. The 2-year follow-up data that were published in 2007 confirmed the disease-free survival benefit (HR, 0.64) and also demonstrated an overall survival benefit (HR, 0.66), the investigators noted.

"The HERA trial results confirm that treatment with adjuvant trastuzumab for 1 year is associated with persisting benefit in women with HER2-positive early breast cancer," the investigators said, concluding that trastuzumab given sequentially to chemotherapy "remains an appropriate treatment modality" in these patients.

They also noted that the possibility that women might derive further benefits from treatment for longer than 1 year is currently being explored in a comparison of the outcomes in the 1-year and 2-year treatment groups of the HERA trial.

F. Hoffmann-La Roche and the Michelangelo Foundation funded the study, which was conducted by the Breast International Group (BIG). Several authors, including Dr. Gianni, reported receiving funding from Roche, such as for advisory board membership, research support, speakers honoraria, consultancy, and travel. One author, Susanne Muehlbauer, is an employee of Roche and has stock options in the company. 

One year of adjuvant trastuzumab following standard chemotherapy is associated with significantly improved long-term, disease-free survival in women with early-stage HER2-positive breast cancer, according to updated findings from the ongoing international, randomized phase III Herceptin Adjuvant trial.

Disease-free survival at a median follow-up of 48.4 months was 78.6% in 1,703 women who were initially randomized to receive 1 year of treatment with trastuzumab (Herceptin) following chemotherapy, compared with 72.2% in 1,698 women randomized to observation following chemotherapy (hazard ratio, 0.76), Dr. Luca Gianni of the Istituto Nazioniale dei Tumori in Milan and colleagues from the HERA Trial Study Team reported online in the Feb. 25 issue of the Lancet Oncology.

Overall survival did not differ significantly between the treatment and observation groups (89.3% and 87.7%, respectively), but the investigators attributed this to the substantial crossover from the observation group to the treatment group after 1-year follow-up results from this study, which were published in 2005.

"This effect was not recorded at 2-year median follow-up, probably because of the short duration of follow-up after crossover at that time" (median, 2.6 moths vs. 29.1 months in this analysis)," they explained.

More than half (52%) of the observation group patients crossed over to receive trastuzumab after the 1-year analysis, beginning treatment at a median of 22.8 months after randomization. Those patients were found in the current study to have fewer disease-free survival events than did those who did not cross over (adjusted hazard ratio, 0.68), the investigators said (Lancet Oncol. 2011 Feb. 25 [doi:10.1016/S1470-2045(11)70033-x]).

Women in the HERA trial had early-stage HER-2-positive breast cancer, an aggressive form of breast cancer that represents about 15%-25% of breast cancers and confers an increased risk of recurrence and mortality. They were enrolled between December 2001 and June 2005, and were randomized to an observation group, a 1-year treatment group, or a 2-year treatment group. Treatment group patients received trastuzumab, a humanized monoclonal antibody that targets the extracellular domain of the HER2 receptor. Treatment was given as an intravenous infusion over 90 minutes every 3 weeks at an initial loading dose of 8 mg/kg and at a dose of 6 mg/kg thereafter.

Trastuzumab was generally well tolerated, although higher incidence of grades 3/4 and fatal adverse events occurred in the 1-year treatment group than in the observation group, they noted, adding that the most common of these – cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhea – each occurred in fewer than 1% of patients.

The interim analysis at 1 year showed that 12 months of treatment with trastuzumab was associated with a 46% reduction in disease recurrence. The 2-year follow-up data that were published in 2007 confirmed the disease-free survival benefit (HR, 0.64) and also demonstrated an overall survival benefit (HR, 0.66), the investigators noted.

"The HERA trial results confirm that treatment with adjuvant trastuzumab for 1 year is associated with persisting benefit in women with HER2-positive early breast cancer," the investigators said, concluding that trastuzumab given sequentially to chemotherapy "remains an appropriate treatment modality" in these patients.

They also noted that the possibility that women might derive further benefits from treatment for longer than 1 year is currently being explored in a comparison of the outcomes in the 1-year and 2-year treatment groups of the HERA trial.

F. Hoffmann-La Roche and the Michelangelo Foundation funded the study, which was conducted by the Breast International Group (BIG). Several authors, including Dr. Gianni, reported receiving funding from Roche, such as for advisory board membership, research support, speakers honoraria, consultancy, and travel. One author, Susanne Muehlbauer, is an employee of Roche and has stock options in the company. 

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.

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 (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

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.

"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.

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 (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

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.

"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.

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 (Circulation 2011 Jan. 25 [doi:10.1161/circulationaha.110.958769]).

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.

"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.

Half of the respondents in a recent survey of more than 43,000 public and private high school students said they had bullied someone in the last year, and 47% said they had been the victim of bullying.

Moreover, 33% of the students surveyed said that violence is a big problem at their school, and 24% said they don’t feel very safe at school, according to the Josephson Institute Center for Youth Ethics, a Los Angeles–based nonprofit, nonpartisan organization that has conducted biannual studies of the ethics of American youth since 1992, and which administers a national values-based program for students titled "CHARACTER COUNTS!"

The problem of bullying, which has garnered a great deal of media attention in the wake of a number of bullying-related incidents – perhaps most notably the suicide of 18-year-old Rutgers University freshman Tyler Clementi in September, after his roommate used a webcam to stream video over the Internet of him during a gay sexual encounter – is one that requires the attention of parents and educators. In fact, on the day the Josephson Institute survey results were released, the U.S. Department of Education issued guidance "to support educators in combating bullying in schools by clarifying when student bullying may violate federal education antidiscrimination laws," according to a press release from the department, and by explaining educators’ legal obligations in regard to protecting students from harassment.

But the problem is one that physicians who care for children also should be addressing routinely, according to Dr. Carl C. Bell, clinical professor of psychiatry and public health, and director of the Institute for Juvenile Research at the University of Illinois at Chicago.

The American Academy of Pediatrics has an anticipatory guidance regarding violence prevention, and this also should apply to bullying, which is a form of violence, Dr. Bell said.

"It should be part of the standard protocol in the office," he said.

The goal should be to ensure that the social fabric that youngsters need for healthy development is in place. "Make sure they are learning social and emotional skills – kids with good people skills can deal with a bully," he said, adding that "catastrophizing" bullying doesn’t fix anything.

Focusing on the effects of bullying can perpetuate the problem. But focusing on what it is that prevents children from being traumatized by it can make a difference, he explained.

The media tend to focus on the catastrophes – the teens who commit suicide. The reality is that suicide rates in teens are about 20 per 100,000, but the attempt rates are 5,000 per 100,000, he said.

"You would think maybe half would complete [suicide] later on, but they don’t," he said, adding that what is stopping them is the social fabric and support systems that are necessary for healthy development.

"Kids with good emotional affect regulation aren’t going to be tripped up, stressed out, or traumatized by a bully," he said.

Physicians can help by encouraging patients to voice their protective factors, he added.

"A lot of the problems we see in children could be curtailed by pediatricians making sure they are in good protective villages, that they have an adult monitoring their behavior, and that they have good skills such as affect regulation. I know pediatricians are not social workers, but ... they have a huge responsibility to try to make sure children are in safe environments, and – equally importantly – in supportive environments that foster emotional, social, mental, and spiritual growth."

That responsibility has particular importance in a society where bullying is no longer defined simply by playground taunts.

The Josephson Institute survey showed that in the prior year, 52% of students had hit a person out of anger, 10% had taken a weapon to school, and 16% admitted to having been under the influence of drugs or alcohol while at school.

The combination of bullying along with these factors significantly increases the likelihood of retaliatory violence, and it’s not only the prevalence of bullying behavior and victimization that’s troublesome, according to Michael Josephson, founder and president of the Institute.

"The Internet has intensified the injury," he said in a statement on the findings.

"What’s posted on the Internet is permanent, and it spreads like a virus – there is no refuge. The difference between the impact of bullying today versus 20 years ago is the difference between getting into a fist fight and using a gun," he said.

Half of the respondents in a recent survey of more than 43,000 public and private high school students said they had bullied someone in the last year, and 47% said they had been the victim of bullying.

Moreover, 33% of the students surveyed said that violence is a big problem at their school, and 24% said they don’t feel very safe at school, according to the Josephson Institute Center for Youth Ethics, a Los Angeles–based nonprofit, nonpartisan organization that has conducted biannual studies of the ethics of American youth since 1992, and which administers a national values-based program for students titled "CHARACTER COUNTS!"

The problem of bullying, which has garnered a great deal of media attention in the wake of a number of bullying-related incidents – perhaps most notably the suicide of 18-year-old Rutgers University freshman Tyler Clementi in September, after his roommate used a webcam to stream video over the Internet of him during a gay sexual encounter – is one that requires the attention of parents and educators. In fact, on the day the Josephson Institute survey results were released, the U.S. Department of Education issued guidance "to support educators in combating bullying in schools by clarifying when student bullying may violate federal education antidiscrimination laws," according to a press release from the department, and by explaining educators’ legal obligations in regard to protecting students from harassment.

But the problem is one that physicians who care for children also should be addressing routinely, according to Dr. Carl C. Bell, clinical professor of psychiatry and public health, and director of the Institute for Juvenile Research at the University of Illinois at Chicago.

The American Academy of Pediatrics has an anticipatory guidance regarding violence prevention, and this also should apply to bullying, which is a form of violence, Dr. Bell said.

"It should be part of the standard protocol in the office," he said.

The goal should be to ensure that the social fabric that youngsters need for healthy development is in place. "Make sure they are learning social and emotional skills – kids with good people skills can deal with a bully," he said, adding that "catastrophizing" bullying doesn’t fix anything.

Focusing on the effects of bullying can perpetuate the problem. But focusing on what it is that prevents children from being traumatized by it can make a difference, he explained.

The media tend to focus on the catastrophes – the teens who commit suicide. The reality is that suicide rates in teens are about 20 per 100,000, but the attempt rates are 5,000 per 100,000, he said.

"You would think maybe half would complete [suicide] later on, but they don’t," he said, adding that what is stopping them is the social fabric and support systems that are necessary for healthy development.

"Kids with good emotional affect regulation aren’t going to be tripped up, stressed out, or traumatized by a bully," he said.

Physicians can help by encouraging patients to voice their protective factors, he added.

"A lot of the problems we see in children could be curtailed by pediatricians making sure they are in good protective villages, that they have an adult monitoring their behavior, and that they have good skills such as affect regulation. I know pediatricians are not social workers, but ... they have a huge responsibility to try to make sure children are in safe environments, and – equally importantly – in supportive environments that foster emotional, social, mental, and spiritual growth."

That responsibility has particular importance in a society where bullying is no longer defined simply by playground taunts.

The Josephson Institute survey showed that in the prior year, 52% of students had hit a person out of anger, 10% had taken a weapon to school, and 16% admitted to having been under the influence of drugs or alcohol while at school.

The combination of bullying along with these factors significantly increases the likelihood of retaliatory violence, and it’s not only the prevalence of bullying behavior and victimization that’s troublesome, according to Michael Josephson, founder and president of the Institute.

"The Internet has intensified the injury," he said in a statement on the findings.

"What’s posted on the Internet is permanent, and it spreads like a virus – there is no refuge. The difference between the impact of bullying today versus 20 years ago is the difference between getting into a fist fight and using a gun," he said.

Half of the respondents in a recent survey of more than 43,000 public and private high school students said they had bullied someone in the last year, and 47% said they had been the victim of bullying.

Moreover, 33% of the students surveyed said that violence is a big problem at their school, and 24% said they don’t feel very safe at school, according to the Josephson Institute Center for Youth Ethics, a Los Angeles–based nonprofit, nonpartisan organization that has conducted biannual studies of the ethics of American youth since 1992, and which administers a national values-based program for students titled "CHARACTER COUNTS!"

The problem of bullying, which has garnered a great deal of media attention in the wake of a number of bullying-related incidents – perhaps most notably the suicide of 18-year-old Rutgers University freshman Tyler Clementi in September, after his roommate used a webcam to stream video over the Internet of him during a gay sexual encounter – is one that requires the attention of parents and educators. In fact, on the day the Josephson Institute survey results were released, the U.S. Department of Education issued guidance "to support educators in combating bullying in schools by clarifying when student bullying may violate federal education antidiscrimination laws," according to a press release from the department, and by explaining educators’ legal obligations in regard to protecting students from harassment.

But the problem is one that physicians who care for children also should be addressing routinely, according to Dr. Carl C. Bell, clinical professor of psychiatry and public health, and director of the Institute for Juvenile Research at the University of Illinois at Chicago.

The American Academy of Pediatrics has an anticipatory guidance regarding violence prevention, and this also should apply to bullying, which is a form of violence, Dr. Bell said.

"It should be part of the standard protocol in the office," he said.

The goal should be to ensure that the social fabric that youngsters need for healthy development is in place. "Make sure they are learning social and emotional skills – kids with good people skills can deal with a bully," he said, adding that "catastrophizing" bullying doesn’t fix anything.

Focusing on the effects of bullying can perpetuate the problem. But focusing on what it is that prevents children from being traumatized by it can make a difference, he explained.

The media tend to focus on the catastrophes – the teens who commit suicide. The reality is that suicide rates in teens are about 20 per 100,000, but the attempt rates are 5,000 per 100,000, he said.

"You would think maybe half would complete [suicide] later on, but they don’t," he said, adding that what is stopping them is the social fabric and support systems that are necessary for healthy development.

"Kids with good emotional affect regulation aren’t going to be tripped up, stressed out, or traumatized by a bully," he said.

Physicians can help by encouraging patients to voice their protective factors, he added.

"A lot of the problems we see in children could be curtailed by pediatricians making sure they are in good protective villages, that they have an adult monitoring their behavior, and that they have good skills such as affect regulation. I know pediatricians are not social workers, but ... they have a huge responsibility to try to make sure children are in safe environments, and – equally importantly – in supportive environments that foster emotional, social, mental, and spiritual growth."

That responsibility has particular importance in a society where bullying is no longer defined simply by playground taunts.

The Josephson Institute survey showed that in the prior year, 52% of students had hit a person out of anger, 10% had taken a weapon to school, and 16% admitted to having been under the influence of drugs or alcohol while at school.

The combination of bullying along with these factors significantly increases the likelihood of retaliatory violence, and it’s not only the prevalence of bullying behavior and victimization that’s troublesome, according to Michael Josephson, founder and president of the Institute.

"The Internet has intensified the injury," he said in a statement on the findings.

"What’s posted on the Internet is permanent, and it spreads like a virus – there is no refuge. The difference between the impact of bullying today versus 20 years ago is the difference between getting into a fist fight and using a gun," he said.

A newly discovered protein variant known as carboxypeptidase E-delta N, or CPE-delta N, appears to be a powerful biomarker for predicting metastasis in patients with hepatocellular carcinoma, pheochromocytoma, paraganglioma, and possibly other types of cancer, a new study shows.

High levels of messenger RNA encoding CPE-Delta N in cancer cells predicted tumor metastasis and recurrence with high sensitivity and specificity in those three specific types of tumors, an international team of investigators reported online in the Feb. 1 issue of the Journal of Clinical Investigation.

High levels also were found in cell lines derived from highly metastatic colon, breast, and head and neck tumors, when compared with matched tumor cell lines with low metastatic potential, said Dr. Terence K. Lee, Dr. Saravana R. K. Murthy, and their colleagues. Dr. Lee is with the University of Hong Kong, Pokfulam, and Dr. Murthy of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Md.

The findings could lead to improvements in cancer treatment via development of new tests for predicting the likelihood of metastasis, as well as new treatments for directly preventing metastasis, the investigators said (J. Clin. Invest. 2011 Feb. 1 [doi:10.1172/JCI40433]).

CPE-delta N is an N-terminal truncated splice isoform of the prohormone processing enzyme carboxypeptidase E. It was found in this study to drive tumor metastasis, invasion, and recurrence.

The investigators measured levels of CPE-delta N RNA in samples from tumors and surrounding tissue from a retrospective cohort of 99 patients with hepatocellular carcinoma (HCC), and found that the CPE-delta N RNA levels were double those in the surrounding tissue in 92% of patients whose cancer recurred or metastasized within 2 years in the tumor samples. Conversely, the levels were less than double in 76% of patients who had no metastasis or recurrence within 2 years. Similar values (sensitivity and specificity of 90% and 78%, respectively) were seen at three years, the investigators found.

In a separate evaluation of 18 patients with stage II liver cancer as determined by conventional staging, 5 were found to have very high levels of CPE-delta N RNA, and 4 of those went on to develop metastasis within 2 years following surgery, Dr. Y. Peng Loh, the senior investigator on the study, said during a telebriefing on the findings.

This is a particularly important finding, because stage II patients generally are thought to have good prognosis following resection, and often don’t receive further treatment after surgery, explained Dr. Loh of the NICHD.

"So CPE-delta N is a better indicator of the seriousness of the disease than [are] current staging techniques, and with more prospective studies, which we are currently doing in collaboration with a liver network in Taiwan, CPE-delta N will likely prove to be a very valuable biomarker in guiding the course of action and treatment for stage II (liver cancer) patients post-surgery, depending on the CPE-delta N RNA levels in their tumor," she said.

Similarly, of 12 patients with stage IV disease, 5 were found to have very low CEP-delta N levels, and those patients had no recurrences in 2 years post-surgery. Generally, stage IV patients have little hope of survival and often don’t receive further treatment because of their prognosis, but a low CEP-delta N level could give "hope of longer survival and psychological comfort."

Furthermore, such a finding might encourage physicians to actively treat these patients with chemotherapy, given their reduced risk of recurrence, she said.

Experiments in mice lend further credence to the conclusion that CPE-delta N levels are associated with metastasis and could lead to the development of treatments to prevent metastasis. Specifically, suppression of the expression of CPE-delta N in liver cancer tumors in the mice was associated with decreased tumor growth and metastasis potential.

Control mice who did not receive CPE-delta N suppression had tumor intensity that was more than 16-fold greater than in treated mice; similarly, mice transplanted with tumor tissue from the control mice had tumor intensity that was nearly 14-fold greater than in mice transplanted with tumor tissue from the treated mice.

"This offers the potential for developing a cure for certain types of cancers using antisense to CPE-delta N to suppress its expression," Dr. Loh said.

To test the effects of CPE-delta N in other types of cancer, the investigators also studied 14 patients with two rare and often deadly types of tumors – pheochromocytomas and paragangliomas (PHEO/PGL), which are tumors of endocrine origin, and for which no reliable markers predict malignant potential.

In these small tumors, surrounding tissue could not be sampled, and therefore the levels of CPE-delta N in those that spread were compared with levels in those that did not spread. CPE-delta N mRNA copy numbers of greater than 1 million/200 mcg of tissue correlated with poor outcome, while copy numbers of less than 250,000/200 mcg of tissue correlated with disease-free survival. Sensitivity and specificity were 100%, Dr. Karel Pacak, another investigator on the study, said during the telebriefing.

Because of the unique nature of these rare tumors, the ability to predict metastasis and recurrence could have "a very important impact on (patient) follow-up as well as treatment options," said Dr. Pacak, also of the NICHD.

The investigators are hopeful that the outcomes of ongoing prospective studies over the next 2-3 years – including possible studies in thyroid, ovarian, and kidney cancer, will lead to the use of CPE-delta N as a biomarker for metastasis in clinical practice in the next few years.

"This biomarker may be useful for many types of cancer, and I think that’s very important," said Dr. Loh, noting that no other accurate biomarker of this type currently exists.

Along with Dr. Pacak and Dr. Stephen M. Hewitt of the Center for Cancer Research in Bethesda, Md., who also spoke during the telebriefing, Dr. Loh stressed that this biomarker is unlike others that have been reported on in the past, but which proved disappointing in their ability to identity and improve prognosis in cancer, because it meets each of 20 criteria (REMARK Criteria) that have been set forth by various cancer societies for reporting on biomarkers, and as required for publication in the Journal of Clinical Investigation.

Indeed, they concluded in their article that "(CPE-delta N’s) assay provides a major breakthrough in biomarker discovery with invaluable utility in cancer prognosis for predicting future metastasis and recurrence in patients with HCC and PHEO/PGL, and potentially for other types of cancer as well."

Still, although CPE-delta N in this study "beats the current standard of care and grading," ... biomarker development – much like drug development – takes time, because outcomes must be determined, Dr. Hewitt said.

"We have a discovery and a very good result, and it’s time to validate this in other cohorts and expand these findings, including to other tumor types," he said.

This study was supported by the National Cancer Institute, the NICHD, the University of Hong Kong, and the Canadian government.

A newly discovered protein variant known as carboxypeptidase E-delta N, or CPE-delta N, appears to be a powerful biomarker for predicting metastasis in patients with hepatocellular carcinoma, pheochromocytoma, paraganglioma, and possibly other types of cancer, a new study shows.

High levels of messenger RNA encoding CPE-Delta N in cancer cells predicted tumor metastasis and recurrence with high sensitivity and specificity in those three specific types of tumors, an international team of investigators reported online in the Feb. 1 issue of the Journal of Clinical Investigation.

High levels also were found in cell lines derived from highly metastatic colon, breast, and head and neck tumors, when compared with matched tumor cell lines with low metastatic potential, said Dr. Terence K. Lee, Dr. Saravana R. K. Murthy, and their colleagues. Dr. Lee is with the University of Hong Kong, Pokfulam, and Dr. Murthy of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Md.

The findings could lead to improvements in cancer treatment via development of new tests for predicting the likelihood of metastasis, as well as new treatments for directly preventing metastasis, the investigators said (J. Clin. Invest. 2011 Feb. 1 [doi:10.1172/JCI40433]).

CPE-delta N is an N-terminal truncated splice isoform of the prohormone processing enzyme carboxypeptidase E. It was found in this study to drive tumor metastasis, invasion, and recurrence.

The investigators measured levels of CPE-delta N RNA in samples from tumors and surrounding tissue from a retrospective cohort of 99 patients with hepatocellular carcinoma (HCC), and found that the CPE-delta N RNA levels were double those in the surrounding tissue in 92% of patients whose cancer recurred or metastasized within 2 years in the tumor samples. Conversely, the levels were less than double in 76% of patients who had no metastasis or recurrence within 2 years. Similar values (sensitivity and specificity of 90% and 78%, respectively) were seen at three years, the investigators found.

In a separate evaluation of 18 patients with stage II liver cancer as determined by conventional staging, 5 were found to have very high levels of CPE-delta N RNA, and 4 of those went on to develop metastasis within 2 years following surgery, Dr. Y. Peng Loh, the senior investigator on the study, said during a telebriefing on the findings.

This is a particularly important finding, because stage II patients generally are thought to have good prognosis following resection, and often don’t receive further treatment after surgery, explained Dr. Loh of the NICHD.

"So CPE-delta N is a better indicator of the seriousness of the disease than [are] current staging techniques, and with more prospective studies, which we are currently doing in collaboration with a liver network in Taiwan, CPE-delta N will likely prove to be a very valuable biomarker in guiding the course of action and treatment for stage II (liver cancer) patients post-surgery, depending on the CPE-delta N RNA levels in their tumor," she said.

Similarly, of 12 patients with stage IV disease, 5 were found to have very low CEP-delta N levels, and those patients had no recurrences in 2 years post-surgery. Generally, stage IV patients have little hope of survival and often don’t receive further treatment because of their prognosis, but a low CEP-delta N level could give "hope of longer survival and psychological comfort."

Furthermore, such a finding might encourage physicians to actively treat these patients with chemotherapy, given their reduced risk of recurrence, she said.

Experiments in mice lend further credence to the conclusion that CPE-delta N levels are associated with metastasis and could lead to the development of treatments to prevent metastasis. Specifically, suppression of the expression of CPE-delta N in liver cancer tumors in the mice was associated with decreased tumor growth and metastasis potential.

Control mice who did not receive CPE-delta N suppression had tumor intensity that was more than 16-fold greater than in treated mice; similarly, mice transplanted with tumor tissue from the control mice had tumor intensity that was nearly 14-fold greater than in mice transplanted with tumor tissue from the treated mice.

"This offers the potential for developing a cure for certain types of cancers using antisense to CPE-delta N to suppress its expression," Dr. Loh said.

To test the effects of CPE-delta N in other types of cancer, the investigators also studied 14 patients with two rare and often deadly types of tumors – pheochromocytomas and paragangliomas (PHEO/PGL), which are tumors of endocrine origin, and for which no reliable markers predict malignant potential.

In these small tumors, surrounding tissue could not be sampled, and therefore the levels of CPE-delta N in those that spread were compared with levels in those that did not spread. CPE-delta N mRNA copy numbers of greater than 1 million/200 mcg of tissue correlated with poor outcome, while copy numbers of less than 250,000/200 mcg of tissue correlated with disease-free survival. Sensitivity and specificity were 100%, Dr. Karel Pacak, another investigator on the study, said during the telebriefing.

Because of the unique nature of these rare tumors, the ability to predict metastasis and recurrence could have "a very important impact on (patient) follow-up as well as treatment options," said Dr. Pacak, also of the NICHD.

The investigators are hopeful that the outcomes of ongoing prospective studies over the next 2-3 years – including possible studies in thyroid, ovarian, and kidney cancer, will lead to the use of CPE-delta N as a biomarker for metastasis in clinical practice in the next few years.

"This biomarker may be useful for many types of cancer, and I think that’s very important," said Dr. Loh, noting that no other accurate biomarker of this type currently exists.

Along with Dr. Pacak and Dr. Stephen M. Hewitt of the Center for Cancer Research in Bethesda, Md., who also spoke during the telebriefing, Dr. Loh stressed that this biomarker is unlike others that have been reported on in the past, but which proved disappointing in their ability to identity and improve prognosis in cancer, because it meets each of 20 criteria (REMARK Criteria) that have been set forth by various cancer societies for reporting on biomarkers, and as required for publication in the Journal of Clinical Investigation.

Indeed, they concluded in their article that "(CPE-delta N’s) assay provides a major breakthrough in biomarker discovery with invaluable utility in cancer prognosis for predicting future metastasis and recurrence in patients with HCC and PHEO/PGL, and potentially for other types of cancer as well."

Still, although CPE-delta N in this study "beats the current standard of care and grading," ... biomarker development – much like drug development – takes time, because outcomes must be determined, Dr. Hewitt said.

"We have a discovery and a very good result, and it’s time to validate this in other cohorts and expand these findings, including to other tumor types," he said.

This study was supported by the National Cancer Institute, the NICHD, the University of Hong Kong, and the Canadian government.

A newly discovered protein variant known as carboxypeptidase E-delta N, or CPE-delta N, appears to be a powerful biomarker for predicting metastasis in patients with hepatocellular carcinoma, pheochromocytoma, paraganglioma, and possibly other types of cancer, a new study shows.

High levels of messenger RNA encoding CPE-Delta N in cancer cells predicted tumor metastasis and recurrence with high sensitivity and specificity in those three specific types of tumors, an international team of investigators reported online in the Feb. 1 issue of the Journal of Clinical Investigation.

High levels also were found in cell lines derived from highly metastatic colon, breast, and head and neck tumors, when compared with matched tumor cell lines with low metastatic potential, said Dr. Terence K. Lee, Dr. Saravana R. K. Murthy, and their colleagues. Dr. Lee is with the University of Hong Kong, Pokfulam, and Dr. Murthy of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Md.

The findings could lead to improvements in cancer treatment via development of new tests for predicting the likelihood of metastasis, as well as new treatments for directly preventing metastasis, the investigators said (J. Clin. Invest. 2011 Feb. 1 [doi:10.1172/JCI40433]).

CPE-delta N is an N-terminal truncated splice isoform of the prohormone processing enzyme carboxypeptidase E. It was found in this study to drive tumor metastasis, invasion, and recurrence.

The investigators measured levels of CPE-delta N RNA in samples from tumors and surrounding tissue from a retrospective cohort of 99 patients with hepatocellular carcinoma (HCC), and found that the CPE-delta N RNA levels were double those in the surrounding tissue in 92% of patients whose cancer recurred or metastasized within 2 years in the tumor samples. Conversely, the levels were less than double in 76% of patients who had no metastasis or recurrence within 2 years. Similar values (sensitivity and specificity of 90% and 78%, respectively) were seen at three years, the investigators found.

In a separate evaluation of 18 patients with stage II liver cancer as determined by conventional staging, 5 were found to have very high levels of CPE-delta N RNA, and 4 of those went on to develop metastasis within 2 years following surgery, Dr. Y. Peng Loh, the senior investigator on the study, said during a telebriefing on the findings.

This is a particularly important finding, because stage II patients generally are thought to have good prognosis following resection, and often don’t receive further treatment after surgery, explained Dr. Loh of the NICHD.

"So CPE-delta N is a better indicator of the seriousness of the disease than [are] current staging techniques, and with more prospective studies, which we are currently doing in collaboration with a liver network in Taiwan, CPE-delta N will likely prove to be a very valuable biomarker in guiding the course of action and treatment for stage II (liver cancer) patients post-surgery, depending on the CPE-delta N RNA levels in their tumor," she said.

Similarly, of 12 patients with stage IV disease, 5 were found to have very low CEP-delta N levels, and those patients had no recurrences in 2 years post-surgery. Generally, stage IV patients have little hope of survival and often don’t receive further treatment because of their prognosis, but a low CEP-delta N level could give "hope of longer survival and psychological comfort."

Furthermore, such a finding might encourage physicians to actively treat these patients with chemotherapy, given their reduced risk of recurrence, she said.

Experiments in mice lend further credence to the conclusion that CPE-delta N levels are associated with metastasis and could lead to the development of treatments to prevent metastasis. Specifically, suppression of the expression of CPE-delta N in liver cancer tumors in the mice was associated with decreased tumor growth and metastasis potential.

Control mice who did not receive CPE-delta N suppression had tumor intensity that was more than 16-fold greater than in treated mice; similarly, mice transplanted with tumor tissue from the control mice had tumor intensity that was nearly 14-fold greater than in mice transplanted with tumor tissue from the treated mice.

"This offers the potential for developing a cure for certain types of cancers using antisense to CPE-delta N to suppress its expression," Dr. Loh said.

To test the effects of CPE-delta N in other types of cancer, the investigators also studied 14 patients with two rare and often deadly types of tumors – pheochromocytomas and paragangliomas (PHEO/PGL), which are tumors of endocrine origin, and for which no reliable markers predict malignant potential.

In these small tumors, surrounding tissue could not be sampled, and therefore the levels of CPE-delta N in those that spread were compared with levels in those that did not spread. CPE-delta N mRNA copy numbers of greater than 1 million/200 mcg of tissue correlated with poor outcome, while copy numbers of less than 250,000/200 mcg of tissue correlated with disease-free survival. Sensitivity and specificity were 100%, Dr. Karel Pacak, another investigator on the study, said during the telebriefing.

Because of the unique nature of these rare tumors, the ability to predict metastasis and recurrence could have "a very important impact on (patient) follow-up as well as treatment options," said Dr. Pacak, also of the NICHD.

The investigators are hopeful that the outcomes of ongoing prospective studies over the next 2-3 years – including possible studies in thyroid, ovarian, and kidney cancer, will lead to the use of CPE-delta N as a biomarker for metastasis in clinical practice in the next few years.

"This biomarker may be useful for many types of cancer, and I think that’s very important," said Dr. Loh, noting that no other accurate biomarker of this type currently exists.

Along with Dr. Pacak and Dr. Stephen M. Hewitt of the Center for Cancer Research in Bethesda, Md., who also spoke during the telebriefing, Dr. Loh stressed that this biomarker is unlike others that have been reported on in the past, but which proved disappointing in their ability to identity and improve prognosis in cancer, because it meets each of 20 criteria (REMARK Criteria) that have been set forth by various cancer societies for reporting on biomarkers, and as required for publication in the Journal of Clinical Investigation.

Indeed, they concluded in their article that "(CPE-delta N’s) assay provides a major breakthrough in biomarker discovery with invaluable utility in cancer prognosis for predicting future metastasis and recurrence in patients with HCC and PHEO/PGL, and potentially for other types of cancer as well."

Still, although CPE-delta N in this study "beats the current standard of care and grading," ... biomarker development – much like drug development – takes time, because outcomes must be determined, Dr. Hewitt said.

"We have a discovery and a very good result, and it’s time to validate this in other cohorts and expand these findings, including to other tumor types," he said.

This study was supported by the National Cancer Institute, the NICHD, the University of Hong Kong, and the Canadian government.

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

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 (at least 30% of total energy) 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.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but in 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 [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 in adolescents was 62–84 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.

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 by adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased HDL cholesterol levels, and increased LDL cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

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 (at least 30% of total energy) 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.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but in 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 [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 in adolescents was 62–84 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.

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 by adolescents is associated with multiple measures known to increase cardiovascular disease risk, including decreased HDL cholesterol levels, and increased LDL cholesterol levels and geometric mean triglyceride levels, according to data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

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 (at least 30% of total energy) 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.

No differences were noted in daily added sugar consumption based on demographic factors including age, sex, race/ethnicity, poverty, or educational level, but in 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 [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 in adolescents was 62–84 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.

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.