Heidi Splete

Major Finding: Individuals in the highest quartile for serum insulin level were 2.8 times more likely to have Barrett's esophagus, compared with those in the lowest quartile.

Data Source: A case-control study including 135 Barrett's esophagus patients, 135 controls with gastroesophageal reflux disease, and 932 controls undergoing colonoscopies.

Disclosures: Dr. Greer stated that she had no financial conflicts of interest.

NEW ORLEANS — High insulin levels, insulin resistance, and central body fat were each significantly associated with an increased risk of Barrett's esophagus in a recent case-control study.

Previous studies have shown that obesity increases the risk of both esophageal adenocarcinoma and its precursor, Barrett's esophagus (BE). In this study, Dr. Katarina Greer and her colleagues investigated whether central adiposity, hyperinsulinemia, and insulin resistance are independent risk factors for BE.

“The mechanism through which obesity promotes cancer is still largely unknown,” said Dr. Greer of University Hospitals Case Medical Center in Cleveland.

The researchers identified 135 adults with BE among consecutive patients seen at a single tertiary care center. The average age of the BE patients was 64 years. These patients were compared with two control groups—135 adults with gastroesophageal reflux disease (GERD) and 932 control adults who were undergoing routine colonoscopies.

Overall, high levels of insulin and insulin resistance were significant independent risk factors for BE, Dr. Greer noted. Individuals in the highest quartile of serum insulin had a 2.8-fold increase in the risk of BE, compared with those in the lowest quartile, when the two control groups were combined in a multivariate analysis controlling for age, sex, and waist-to-hip ratio.

Regarding insulin resistance, individuals in the highest quartile of values for the homeostasis model assessment–insulin resistance (HOMA-IR) were about three times more likely to develop BE, compared with those in the lowest quartile.

HOMA-IR was calculated using baseline fasting insulin and glucose levels. Mean fasting insulin levels were significantly higher in BE patients vs. colonoscopy patients (10.1 vs. 7.4 microIU/mL).

In addition, BE patients were more insulin resistant than either of the control groups. The mean HOMA-IR in the BE group was 2.7, compared with 1.8 for the control groups.

The average body mass index was 30.8 kg/m

The findings support existing evidence of a connection between insulin and cancer, but additional studies are needed to examine whether losing weight and treating insulin resistance can disrupt or reverse progression to cancer in BE patients, Dr. Greer said.

Major Finding: Individuals in the highest quartile for serum insulin level were 2.8 times more likely to have Barrett's esophagus, compared with those in the lowest quartile.

Data Source: A case-control study including 135 Barrett's esophagus patients, 135 controls with gastroesophageal reflux disease, and 932 controls undergoing colonoscopies.

Disclosures: Dr. Greer stated that she had no financial conflicts of interest.

NEW ORLEANS — High insulin levels, insulin resistance, and central body fat were each significantly associated with an increased risk of Barrett's esophagus in a recent case-control study.

Previous studies have shown that obesity increases the risk of both esophageal adenocarcinoma and its precursor, Barrett's esophagus (BE). In this study, Dr. Katarina Greer and her colleagues investigated whether central adiposity, hyperinsulinemia, and insulin resistance are independent risk factors for BE.

“The mechanism through which obesity promotes cancer is still largely unknown,” said Dr. Greer of University Hospitals Case Medical Center in Cleveland.

The researchers identified 135 adults with BE among consecutive patients seen at a single tertiary care center. The average age of the BE patients was 64 years. These patients were compared with two control groups—135 adults with gastroesophageal reflux disease (GERD) and 932 control adults who were undergoing routine colonoscopies.

Overall, high levels of insulin and insulin resistance were significant independent risk factors for BE, Dr. Greer noted. Individuals in the highest quartile of serum insulin had a 2.8-fold increase in the risk of BE, compared with those in the lowest quartile, when the two control groups were combined in a multivariate analysis controlling for age, sex, and waist-to-hip ratio.

Regarding insulin resistance, individuals in the highest quartile of values for the homeostasis model assessment–insulin resistance (HOMA-IR) were about three times more likely to develop BE, compared with those in the lowest quartile.

HOMA-IR was calculated using baseline fasting insulin and glucose levels. Mean fasting insulin levels were significantly higher in BE patients vs. colonoscopy patients (10.1 vs. 7.4 microIU/mL).

In addition, BE patients were more insulin resistant than either of the control groups. The mean HOMA-IR in the BE group was 2.7, compared with 1.8 for the control groups.

The average body mass index was 30.8 kg/m

The findings support existing evidence of a connection between insulin and cancer, but additional studies are needed to examine whether losing weight and treating insulin resistance can disrupt or reverse progression to cancer in BE patients, Dr. Greer said.

Major Finding: Individuals in the highest quartile for serum insulin level were 2.8 times more likely to have Barrett's esophagus, compared with those in the lowest quartile.

Data Source: A case-control study including 135 Barrett's esophagus patients, 135 controls with gastroesophageal reflux disease, and 932 controls undergoing colonoscopies.

Disclosures: Dr. Greer stated that she had no financial conflicts of interest.

NEW ORLEANS — High insulin levels, insulin resistance, and central body fat were each significantly associated with an increased risk of Barrett's esophagus in a recent case-control study.

Previous studies have shown that obesity increases the risk of both esophageal adenocarcinoma and its precursor, Barrett's esophagus (BE). In this study, Dr. Katarina Greer and her colleagues investigated whether central adiposity, hyperinsulinemia, and insulin resistance are independent risk factors for BE.

“The mechanism through which obesity promotes cancer is still largely unknown,” said Dr. Greer of University Hospitals Case Medical Center in Cleveland.

The researchers identified 135 adults with BE among consecutive patients seen at a single tertiary care center. The average age of the BE patients was 64 years. These patients were compared with two control groups—135 adults with gastroesophageal reflux disease (GERD) and 932 control adults who were undergoing routine colonoscopies.

Overall, high levels of insulin and insulin resistance were significant independent risk factors for BE, Dr. Greer noted. Individuals in the highest quartile of serum insulin had a 2.8-fold increase in the risk of BE, compared with those in the lowest quartile, when the two control groups were combined in a multivariate analysis controlling for age, sex, and waist-to-hip ratio.

Regarding insulin resistance, individuals in the highest quartile of values for the homeostasis model assessment–insulin resistance (HOMA-IR) were about three times more likely to develop BE, compared with those in the lowest quartile.

HOMA-IR was calculated using baseline fasting insulin and glucose levels. Mean fasting insulin levels were significantly higher in BE patients vs. colonoscopy patients (10.1 vs. 7.4 microIU/mL).

In addition, BE patients were more insulin resistant than either of the control groups. The mean HOMA-IR in the BE group was 2.7, compared with 1.8 for the control groups.

The average body mass index was 30.8 kg/m

The findings support existing evidence of a connection between insulin and cancer, but additional studies are needed to examine whether losing weight and treating insulin resistance can disrupt or reverse progression to cancer in BE patients, Dr. Greer said.

Major Finding: Risk of progression at 24 months was 31% higher with thalidomide than with tamoxifen in women with recurrent, asymptomatic ovarian cancer.

Data Source: A phase III GOG trial in 138 patients.

Disclosures: None was reported.

SAN FRANCISCO — Oral thalidomide was associated with more severe toxicity and a significantly increased risk of disease progression and death, compared with tamoxifen, in a phase III trial conducted in women with recurrent, asymptomatic ovarian cancer.

“Tamoxifen may be a reasonable treatment alternative for patients with biochemical-recurrent ovarian cancer,” said Dr. Jean Hurteau of the North Shore University Health System in Chicago. But he cautioned that the findings need to be validated in other randomized trials.

Tamoxifen plays an important role in the treatment of hormone-driven breast cancer, but evidence for its use in recurrent ovarian cancer is lacking, according to a Cochrane Review article in which the authors found no randomized trials on which to base recommendations (2010 [doi:10.1002/14651858.CD001034.pub2]).

The rationale for the current trial was that the comparative effectiveness of tamoxifen (a hormonal therapy) and thalidomide (an antiangiogenesis agent) was not known in recurrent ovarian cancer.

All participants had biochemical-recurrent ovarian cancer (defined as a rise in CA 125 of at least twice the upper limit of normal with no evidence of disease by RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Dr. Hurteau and his coinvestigators from the GOG (Gynecologic Oncology Group) 198 trial reported on 68 women who were randomized to receive a minimum of 200 mg of oral thalidomide once daily (with a weekly dose escalation of 100 mg to a maximum of 400 mg), and 70 women randomized to receive 20 mg of oral tamoxifen twice daily.

The study group included women with FIGO stage III or IV confirmed epithelial ovarian, tubal, or primary peritoneal cancer who had completed first-line chemotherapy and whose CA 125 had normalized. The average age of the patients was 64 years, and 67% had grade III tumors, Dr. Hurteau said.

The women were assessed for toxicity every 4 weeks, and for disease progression every 12 weeks, until either disease progression or death.

Women who received thalidomide had a 31% increased risk of disease progression (hazard ratio, 1.31), compared with those who were given tamoxifen. Median progression-free survival was 3.2 months in the thalidomide group vs. 4.5 months in the tamoxifen group.

In terms of overall survival, women in the thalidomide group had a 76% increased risk of death (HR, 1.76) after 48 months, compared with those who took tamoxifen.

In addition, women in the thalidomide group experienced more grade III/IV toxicity, compared with the tamoxifen group (55% vs. 3%). Venous thromboembolism occurred in 6% of the thalidomide group and 1.4% of the tamoxifen group.

Major Finding: Risk of progression at 24 months was 31% higher with thalidomide than with tamoxifen in women with recurrent, asymptomatic ovarian cancer.

Data Source: A phase III GOG trial in 138 patients.

Disclosures: None was reported.

SAN FRANCISCO — Oral thalidomide was associated with more severe toxicity and a significantly increased risk of disease progression and death, compared with tamoxifen, in a phase III trial conducted in women with recurrent, asymptomatic ovarian cancer.

“Tamoxifen may be a reasonable treatment alternative for patients with biochemical-recurrent ovarian cancer,” said Dr. Jean Hurteau of the North Shore University Health System in Chicago. But he cautioned that the findings need to be validated in other randomized trials.

Tamoxifen plays an important role in the treatment of hormone-driven breast cancer, but evidence for its use in recurrent ovarian cancer is lacking, according to a Cochrane Review article in which the authors found no randomized trials on which to base recommendations (2010 [doi:10.1002/14651858.CD001034.pub2]).

The rationale for the current trial was that the comparative effectiveness of tamoxifen (a hormonal therapy) and thalidomide (an antiangiogenesis agent) was not known in recurrent ovarian cancer.

All participants had biochemical-recurrent ovarian cancer (defined as a rise in CA 125 of at least twice the upper limit of normal with no evidence of disease by RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Dr. Hurteau and his coinvestigators from the GOG (Gynecologic Oncology Group) 198 trial reported on 68 women who were randomized to receive a minimum of 200 mg of oral thalidomide once daily (with a weekly dose escalation of 100 mg to a maximum of 400 mg), and 70 women randomized to receive 20 mg of oral tamoxifen twice daily.

The study group included women with FIGO stage III or IV confirmed epithelial ovarian, tubal, or primary peritoneal cancer who had completed first-line chemotherapy and whose CA 125 had normalized. The average age of the patients was 64 years, and 67% had grade III tumors, Dr. Hurteau said.

The women were assessed for toxicity every 4 weeks, and for disease progression every 12 weeks, until either disease progression or death.

Women who received thalidomide had a 31% increased risk of disease progression (hazard ratio, 1.31), compared with those who were given tamoxifen. Median progression-free survival was 3.2 months in the thalidomide group vs. 4.5 months in the tamoxifen group.

In terms of overall survival, women in the thalidomide group had a 76% increased risk of death (HR, 1.76) after 48 months, compared with those who took tamoxifen.

In addition, women in the thalidomide group experienced more grade III/IV toxicity, compared with the tamoxifen group (55% vs. 3%). Venous thromboembolism occurred in 6% of the thalidomide group and 1.4% of the tamoxifen group.

Major Finding: Risk of progression at 24 months was 31% higher with thalidomide than with tamoxifen in women with recurrent, asymptomatic ovarian cancer.

Data Source: A phase III GOG trial in 138 patients.

Disclosures: None was reported.

SAN FRANCISCO — Oral thalidomide was associated with more severe toxicity and a significantly increased risk of disease progression and death, compared with tamoxifen, in a phase III trial conducted in women with recurrent, asymptomatic ovarian cancer.

“Tamoxifen may be a reasonable treatment alternative for patients with biochemical-recurrent ovarian cancer,” said Dr. Jean Hurteau of the North Shore University Health System in Chicago. But he cautioned that the findings need to be validated in other randomized trials.

Tamoxifen plays an important role in the treatment of hormone-driven breast cancer, but evidence for its use in recurrent ovarian cancer is lacking, according to a Cochrane Review article in which the authors found no randomized trials on which to base recommendations (2010 [doi:10.1002/14651858.CD001034.pub2]).

The rationale for the current trial was that the comparative effectiveness of tamoxifen (a hormonal therapy) and thalidomide (an antiangiogenesis agent) was not known in recurrent ovarian cancer.

All participants had biochemical-recurrent ovarian cancer (defined as a rise in CA 125 of at least twice the upper limit of normal with no evidence of disease by RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Dr. Hurteau and his coinvestigators from the GOG (Gynecologic Oncology Group) 198 trial reported on 68 women who were randomized to receive a minimum of 200 mg of oral thalidomide once daily (with a weekly dose escalation of 100 mg to a maximum of 400 mg), and 70 women randomized to receive 20 mg of oral tamoxifen twice daily.

The study group included women with FIGO stage III or IV confirmed epithelial ovarian, tubal, or primary peritoneal cancer who had completed first-line chemotherapy and whose CA 125 had normalized. The average age of the patients was 64 years, and 67% had grade III tumors, Dr. Hurteau said.

The women were assessed for toxicity every 4 weeks, and for disease progression every 12 weeks, until either disease progression or death.

Women who received thalidomide had a 31% increased risk of disease progression (hazard ratio, 1.31), compared with those who were given tamoxifen. Median progression-free survival was 3.2 months in the thalidomide group vs. 4.5 months in the tamoxifen group.

In terms of overall survival, women in the thalidomide group had a 76% increased risk of death (HR, 1.76) after 48 months, compared with those who took tamoxifen.

In addition, women in the thalidomide group experienced more grade III/IV toxicity, compared with the tamoxifen group (55% vs. 3%). Venous thromboembolism occurred in 6% of the thalidomide group and 1.4% of the tamoxifen group.

Major Finding: A total of 96 of 126 cases of VTE occurred more than a week after gynecologic cancer surgery.

Data Source: A nested case-control study based on a sample of 4,162 women who underwent major gynecologic cancer surgery.

Disclosures: None was reported.

SAN FRANCISCO — More than 75% of venous thromboembolisms linked to gynecologic cancer surgery occur more than a week after the procedure, based on data from 4,162 women aged 18 years and older who had undergone major gynecologic surgery between 1998 and 2008 at a single institution.

Few studies have addressed long-term postoperative risk of venous thromboembolism (VTE), and prolonged prophylaxis might be warranted for high-risk cancer patients, said Dr. Abraham Peedicayil of the Mayo Clinic in Rochester, Minn.

To determine risk factors, timing, and incidence of late VTE, Dr. Peedicayil and his colleagues conducted a nested case-control study of 126 patients who had VTE within 90 days of surgery (an incidence of 3.03%) and matched controls who did not experience VTE.

The average age of the patients was 61 years.

Overall, 30 cases of VTE occurred on days 1-7 after surgery; 50 cases, on days 8-21; and 46, on days 22-90.

Based on location of the surgery, ovarian cancer patients had nearly two-thirds (64%) of the VTEs that occurred within the first week after surgery. Patients with uterine cancers accounted for one-third (33%) of the VTEs that occurred this early, and those with cervical cancers including the cervix, vulva, and vagina made up a smaller group (3%).

But the proportion of VTEs in ovarian cancers decreased over time, to 58% during days 8-28 and 41% during days 29-90.

By contrast, the likelihood of VTE in cervical cancer patients increased over time, to 8% of all VTEs during days 8-28 and 20% during days 29-90, Dr. Peedicayil reported.

In a univariate analysis, ovarian cancer (including ovarian, tubal, and peritoneal) was an independent risk factor for VTE overall (P = .02) and on days 8-90 (P = .04).

In a multivariate analysis, independent risk factors for VTE included a previous VTE (P = .03), blood loss of 500 mL or greater (P = .044), and a hospital stay of more than 5 days (P = .044), but only the hospital stay reached statistical significance, and only for the period from days 8 to 28 after surgery (P = .002).

In all three time periods, incidence of VTEs increased with age; more than half (range, 57%-70%) occurred in women older than 60 years.

The results suggest that the majority of cases of VTE occur more than a week after surgery, beyond the time when most patients have been discharged, Dr. Peedicayil said. The findings support the use of prolonged VTE prophylaxis for high-risk patients, but more research is needed to define the highest-risk patients and to identify a more precise duration of VTE.

Major Finding: A total of 96 of 126 cases of VTE occurred more than a week after gynecologic cancer surgery.

Data Source: A nested case-control study based on a sample of 4,162 women who underwent major gynecologic cancer surgery.

Disclosures: None was reported.

SAN FRANCISCO — More than 75% of venous thromboembolisms linked to gynecologic cancer surgery occur more than a week after the procedure, based on data from 4,162 women aged 18 years and older who had undergone major gynecologic surgery between 1998 and 2008 at a single institution.

Few studies have addressed long-term postoperative risk of venous thromboembolism (VTE), and prolonged prophylaxis might be warranted for high-risk cancer patients, said Dr. Abraham Peedicayil of the Mayo Clinic in Rochester, Minn.

To determine risk factors, timing, and incidence of late VTE, Dr. Peedicayil and his colleagues conducted a nested case-control study of 126 patients who had VTE within 90 days of surgery (an incidence of 3.03%) and matched controls who did not experience VTE.

The average age of the patients was 61 years.

Overall, 30 cases of VTE occurred on days 1-7 after surgery; 50 cases, on days 8-21; and 46, on days 22-90.

Based on location of the surgery, ovarian cancer patients had nearly two-thirds (64%) of the VTEs that occurred within the first week after surgery. Patients with uterine cancers accounted for one-third (33%) of the VTEs that occurred this early, and those with cervical cancers including the cervix, vulva, and vagina made up a smaller group (3%).

But the proportion of VTEs in ovarian cancers decreased over time, to 58% during days 8-28 and 41% during days 29-90.

By contrast, the likelihood of VTE in cervical cancer patients increased over time, to 8% of all VTEs during days 8-28 and 20% during days 29-90, Dr. Peedicayil reported.

In a univariate analysis, ovarian cancer (including ovarian, tubal, and peritoneal) was an independent risk factor for VTE overall (P = .02) and on days 8-90 (P = .04).

In a multivariate analysis, independent risk factors for VTE included a previous VTE (P = .03), blood loss of 500 mL or greater (P = .044), and a hospital stay of more than 5 days (P = .044), but only the hospital stay reached statistical significance, and only for the period from days 8 to 28 after surgery (P = .002).

In all three time periods, incidence of VTEs increased with age; more than half (range, 57%-70%) occurred in women older than 60 years.

The results suggest that the majority of cases of VTE occur more than a week after surgery, beyond the time when most patients have been discharged, Dr. Peedicayil said. The findings support the use of prolonged VTE prophylaxis for high-risk patients, but more research is needed to define the highest-risk patients and to identify a more precise duration of VTE.

Major Finding: A total of 96 of 126 cases of VTE occurred more than a week after gynecologic cancer surgery.

Data Source: A nested case-control study based on a sample of 4,162 women who underwent major gynecologic cancer surgery.

Disclosures: None was reported.

SAN FRANCISCO — More than 75% of venous thromboembolisms linked to gynecologic cancer surgery occur more than a week after the procedure, based on data from 4,162 women aged 18 years and older who had undergone major gynecologic surgery between 1998 and 2008 at a single institution.

Few studies have addressed long-term postoperative risk of venous thromboembolism (VTE), and prolonged prophylaxis might be warranted for high-risk cancer patients, said Dr. Abraham Peedicayil of the Mayo Clinic in Rochester, Minn.

To determine risk factors, timing, and incidence of late VTE, Dr. Peedicayil and his colleagues conducted a nested case-control study of 126 patients who had VTE within 90 days of surgery (an incidence of 3.03%) and matched controls who did not experience VTE.

The average age of the patients was 61 years.

Overall, 30 cases of VTE occurred on days 1-7 after surgery; 50 cases, on days 8-21; and 46, on days 22-90.

Based on location of the surgery, ovarian cancer patients had nearly two-thirds (64%) of the VTEs that occurred within the first week after surgery. Patients with uterine cancers accounted for one-third (33%) of the VTEs that occurred this early, and those with cervical cancers including the cervix, vulva, and vagina made up a smaller group (3%).

But the proportion of VTEs in ovarian cancers decreased over time, to 58% during days 8-28 and 41% during days 29-90.

By contrast, the likelihood of VTE in cervical cancer patients increased over time, to 8% of all VTEs during days 8-28 and 20% during days 29-90, Dr. Peedicayil reported.

In a univariate analysis, ovarian cancer (including ovarian, tubal, and peritoneal) was an independent risk factor for VTE overall (P = .02) and on days 8-90 (P = .04).

In a multivariate analysis, independent risk factors for VTE included a previous VTE (P = .03), blood loss of 500 mL or greater (P = .044), and a hospital stay of more than 5 days (P = .044), but only the hospital stay reached statistical significance, and only for the period from days 8 to 28 after surgery (P = .002).

In all three time periods, incidence of VTEs increased with age; more than half (range, 57%-70%) occurred in women older than 60 years.

The results suggest that the majority of cases of VTE occur more than a week after surgery, beyond the time when most patients have been discharged, Dr. Peedicayil said. The findings support the use of prolonged VTE prophylaxis for high-risk patients, but more research is needed to define the highest-risk patients and to identify a more precise duration of VTE.

NEW ORLEANS — Inhaled corticosteroids were significantly more effective than systemic corticosteroids in preventing hospitalization of children who presented to the emergency department with acute asthma exacerbation, based on a review of data from 10 studies including more than 1,000 children aged 6 months to 18 years.

Corticosteroids are widely used to treat pediatric asthma, but the efficacy of different routes of administration in an emergency department (ED) setting has not been well studied, noted Dr. Rabia Q. Chaudhry of the New Jersey Medical School, Newark. He and his associates reviewed 10 studies conducted between 1986 and 2009, including 388 patients treated with inhaled corticosteroids (ICS), 337 treated with systemic corticosteroids (SCS), and 298 treated with a placebo. The likelihood of hospitalization was significantly lower (40% reduced risk) in children who received ICS vs. SCS (14% vs. 21%). “The number needed to treat to prevent one hospitalization of a child with acute asthma exacerbation is five for ICS and eight for SCS,” they noted in a poster presentation.

Regardless of the delivery route, hospitalization rates were significantly higher in children who received a placebo (33%). Hospitalization rates ranged from 23% to 49% in the placebo group, 10% to 30% in the SCS group, and 0% to 32% in the ICS group across all the studies.

Studies that compared a combination of ICS and SCS to SCS alone were excluded from this analysis. The results were limited by the variation in sample sizes, and by the different brands of medications used in different studies, they said.

The investigators reported no relevant financial disclosures.

NEW ORLEANS — Inhaled corticosteroids were significantly more effective than systemic corticosteroids in preventing hospitalization of children who presented to the emergency department with acute asthma exacerbation, based on a review of data from 10 studies including more than 1,000 children aged 6 months to 18 years.

Corticosteroids are widely used to treat pediatric asthma, but the efficacy of different routes of administration in an emergency department (ED) setting has not been well studied, noted Dr. Rabia Q. Chaudhry of the New Jersey Medical School, Newark. He and his associates reviewed 10 studies conducted between 1986 and 2009, including 388 patients treated with inhaled corticosteroids (ICS), 337 treated with systemic corticosteroids (SCS), and 298 treated with a placebo. The likelihood of hospitalization was significantly lower (40% reduced risk) in children who received ICS vs. SCS (14% vs. 21%). “The number needed to treat to prevent one hospitalization of a child with acute asthma exacerbation is five for ICS and eight for SCS,” they noted in a poster presentation.

Regardless of the delivery route, hospitalization rates were significantly higher in children who received a placebo (33%). Hospitalization rates ranged from 23% to 49% in the placebo group, 10% to 30% in the SCS group, and 0% to 32% in the ICS group across all the studies.

Studies that compared a combination of ICS and SCS to SCS alone were excluded from this analysis. The results were limited by the variation in sample sizes, and by the different brands of medications used in different studies, they said.

The investigators reported no relevant financial disclosures.

NEW ORLEANS — Inhaled corticosteroids were significantly more effective than systemic corticosteroids in preventing hospitalization of children who presented to the emergency department with acute asthma exacerbation, based on a review of data from 10 studies including more than 1,000 children aged 6 months to 18 years.

Corticosteroids are widely used to treat pediatric asthma, but the efficacy of different routes of administration in an emergency department (ED) setting has not been well studied, noted Dr. Rabia Q. Chaudhry of the New Jersey Medical School, Newark. He and his associates reviewed 10 studies conducted between 1986 and 2009, including 388 patients treated with inhaled corticosteroids (ICS), 337 treated with systemic corticosteroids (SCS), and 298 treated with a placebo. The likelihood of hospitalization was significantly lower (40% reduced risk) in children who received ICS vs. SCS (14% vs. 21%). “The number needed to treat to prevent one hospitalization of a child with acute asthma exacerbation is five for ICS and eight for SCS,” they noted in a poster presentation.

Regardless of the delivery route, hospitalization rates were significantly higher in children who received a placebo (33%). Hospitalization rates ranged from 23% to 49% in the placebo group, 10% to 30% in the SCS group, and 0% to 32% in the ICS group across all the studies.

Studies that compared a combination of ICS and SCS to SCS alone were excluded from this analysis. The results were limited by the variation in sample sizes, and by the different brands of medications used in different studies, they said.

The investigators reported no relevant financial disclosures.

Major Finding: The relative risk for developing IBD was 3.31 for high total protein intake and 3.03 for high animal protein intake, when comparing the highest tertile of intake with the lowest tertile of intake.

Data Source: A prospective study of a cohort of approximately 60,000 women aged 40–65 years, 77 of whom developed IBD during a mean follow-up of 10 years.

Disclosures: Dr. Jantchou said that he had no financial conflicts to disclose.

High intake of animal protein was significantly associated with increased risk of developing inflammatory bowel disease in a prospective study of more than 60,000 women aged 40–65 years, 77 of whom developed IBD.

Although doctors have long suspected an association between diet and inflammatory bowel disease (IBD), most previous studies on this topic have been retrospective, said Dr. Prvost Jantchou of the Centre for Research in Epidemiology and Population Health in Villejuif, France.

In this prospective study, onset of IBD occurred after the first dietary questionnaire was completed by each participant, so it was not necessary for the women to try to recall what they had eaten in the past—a common source of error in retrospective studies.

The 77 cases, all of whom developed confirmed IBD, were part of the E3N study, a cohort of more than 60,000 women that was established in France in 1990 to assess risk factors for female cancers. The controls were all the women in the cohort of 60,000 who did not state that they had developed IBD by 2005, the final follow-up. A Cox survival model analysis was performed.

The participants completed questionnaires about diet, disease incidence, and lifestyle every 2 years until 2005. The average follow-up period for the women in this study was 10 years.

Dr. Jantchou and colleagues examined participants' intake of protein, carbohydrate, and fat. Then the subjects were divided into three groups based on protein intake. The average intake of the low, middle, and high tertiles was 1.08 g/kg, 1.52 g/kg, and 2.07 g/kg, respectively. The Food and Drug Administration recommends an average daily protein intake of 0.8 g/kg of body weight, he said.

More than two-thirds of the 77 participants who developed IBD had an elevated protein intake, Dr. Jantchou noted. Mean total protein intake was 102.4 g/day for IBD cases vs. 92.1 g/day for controls, Dr. Jantchou said in an interview. Animal protein intake also was higher for the women who developed IBD during the study: 70.1 g/day, vs. 61.9 g/day for the controls, he said.

Overall, a high intake of animal protein was associated with a significantly increased risk of IBD. The relative risks for the highest tertile of intake vs. the lowest tertile were 3.31 for total protein intake and 3.03 for animal protein intake specifically. The associations remained significant after researchers controlled for smoking and hormone therapy, both of which can increase the risk for IBD.

When the investigators looked at specific animal proteins, they found that higher than average consumption of meat or fish was associated with a significantly increased risk of IBD but the high consumption of dairy products or eggs was not, Dr. Jantchou said.

When IBD was broken down into Crohn's disease and ulcerative colitis, similar results were seen for both diseases: High intake of animal protein was associated with an increased risk of each disease. The researchers found no association between either carbohydrate intake or fat intake and risk of IBD, he noted.

This study is the first to prospectively show an association between a high intake of animal protein and an increased risk of IBD, Dr. Jantchou said. “The next step we want to take is to look at animal protein in patients already diagnosed with IBD and to give them dietary advice,” Dr. Jantchou added.

Major Finding: The relative risk for developing IBD was 3.31 for high total protein intake and 3.03 for high animal protein intake, when comparing the highest tertile of intake with the lowest tertile of intake.

Data Source: A prospective study of a cohort of approximately 60,000 women aged 40–65 years, 77 of whom developed IBD during a mean follow-up of 10 years.

Disclosures: Dr. Jantchou said that he had no financial conflicts to disclose.

High intake of animal protein was significantly associated with increased risk of developing inflammatory bowel disease in a prospective study of more than 60,000 women aged 40–65 years, 77 of whom developed IBD.

Although doctors have long suspected an association between diet and inflammatory bowel disease (IBD), most previous studies on this topic have been retrospective, said Dr. Prvost Jantchou of the Centre for Research in Epidemiology and Population Health in Villejuif, France.

In this prospective study, onset of IBD occurred after the first dietary questionnaire was completed by each participant, so it was not necessary for the women to try to recall what they had eaten in the past—a common source of error in retrospective studies.

The 77 cases, all of whom developed confirmed IBD, were part of the E3N study, a cohort of more than 60,000 women that was established in France in 1990 to assess risk factors for female cancers. The controls were all the women in the cohort of 60,000 who did not state that they had developed IBD by 2005, the final follow-up. A Cox survival model analysis was performed.

The participants completed questionnaires about diet, disease incidence, and lifestyle every 2 years until 2005. The average follow-up period for the women in this study was 10 years.

Dr. Jantchou and colleagues examined participants' intake of protein, carbohydrate, and fat. Then the subjects were divided into three groups based on protein intake. The average intake of the low, middle, and high tertiles was 1.08 g/kg, 1.52 g/kg, and 2.07 g/kg, respectively. The Food and Drug Administration recommends an average daily protein intake of 0.8 g/kg of body weight, he said.

More than two-thirds of the 77 participants who developed IBD had an elevated protein intake, Dr. Jantchou noted. Mean total protein intake was 102.4 g/day for IBD cases vs. 92.1 g/day for controls, Dr. Jantchou said in an interview. Animal protein intake also was higher for the women who developed IBD during the study: 70.1 g/day, vs. 61.9 g/day for the controls, he said.

Overall, a high intake of animal protein was associated with a significantly increased risk of IBD. The relative risks for the highest tertile of intake vs. the lowest tertile were 3.31 for total protein intake and 3.03 for animal protein intake specifically. The associations remained significant after researchers controlled for smoking and hormone therapy, both of which can increase the risk for IBD.

When the investigators looked at specific animal proteins, they found that higher than average consumption of meat or fish was associated with a significantly increased risk of IBD but the high consumption of dairy products or eggs was not, Dr. Jantchou said.

When IBD was broken down into Crohn's disease and ulcerative colitis, similar results were seen for both diseases: High intake of animal protein was associated with an increased risk of each disease. The researchers found no association between either carbohydrate intake or fat intake and risk of IBD, he noted.

This study is the first to prospectively show an association between a high intake of animal protein and an increased risk of IBD, Dr. Jantchou said. “The next step we want to take is to look at animal protein in patients already diagnosed with IBD and to give them dietary advice,” Dr. Jantchou added.

Major Finding: The relative risk for developing IBD was 3.31 for high total protein intake and 3.03 for high animal protein intake, when comparing the highest tertile of intake with the lowest tertile of intake.

Data Source: A prospective study of a cohort of approximately 60,000 women aged 40–65 years, 77 of whom developed IBD during a mean follow-up of 10 years.

Disclosures: Dr. Jantchou said that he had no financial conflicts to disclose.

High intake of animal protein was significantly associated with increased risk of developing inflammatory bowel disease in a prospective study of more than 60,000 women aged 40–65 years, 77 of whom developed IBD.

Although doctors have long suspected an association between diet and inflammatory bowel disease (IBD), most previous studies on this topic have been retrospective, said Dr. Prvost Jantchou of the Centre for Research in Epidemiology and Population Health in Villejuif, France.

In this prospective study, onset of IBD occurred after the first dietary questionnaire was completed by each participant, so it was not necessary for the women to try to recall what they had eaten in the past—a common source of error in retrospective studies.

The 77 cases, all of whom developed confirmed IBD, were part of the E3N study, a cohort of more than 60,000 women that was established in France in 1990 to assess risk factors for female cancers. The controls were all the women in the cohort of 60,000 who did not state that they had developed IBD by 2005, the final follow-up. A Cox survival model analysis was performed.

The participants completed questionnaires about diet, disease incidence, and lifestyle every 2 years until 2005. The average follow-up period for the women in this study was 10 years.

Dr. Jantchou and colleagues examined participants' intake of protein, carbohydrate, and fat. Then the subjects were divided into three groups based on protein intake. The average intake of the low, middle, and high tertiles was 1.08 g/kg, 1.52 g/kg, and 2.07 g/kg, respectively. The Food and Drug Administration recommends an average daily protein intake of 0.8 g/kg of body weight, he said.

More than two-thirds of the 77 participants who developed IBD had an elevated protein intake, Dr. Jantchou noted. Mean total protein intake was 102.4 g/day for IBD cases vs. 92.1 g/day for controls, Dr. Jantchou said in an interview. Animal protein intake also was higher for the women who developed IBD during the study: 70.1 g/day, vs. 61.9 g/day for the controls, he said.

Overall, a high intake of animal protein was associated with a significantly increased risk of IBD. The relative risks for the highest tertile of intake vs. the lowest tertile were 3.31 for total protein intake and 3.03 for animal protein intake specifically. The associations remained significant after researchers controlled for smoking and hormone therapy, both of which can increase the risk for IBD.

When the investigators looked at specific animal proteins, they found that higher than average consumption of meat or fish was associated with a significantly increased risk of IBD but the high consumption of dairy products or eggs was not, Dr. Jantchou said.

When IBD was broken down into Crohn's disease and ulcerative colitis, similar results were seen for both diseases: High intake of animal protein was associated with an increased risk of each disease. The researchers found no association between either carbohydrate intake or fat intake and risk of IBD, he noted.

This study is the first to prospectively show an association between a high intake of animal protein and an increased risk of IBD, Dr. Jantchou said. “The next step we want to take is to look at animal protein in patients already diagnosed with IBD and to give them dietary advice,” Dr. Jantchou added.

ORLANDO — Obstructive sleep apnea patients with symptoms of excessive sleepiness have the greatest risk of depression, based on data from a prospective study of 107 adults.

Data from previous studies have shown that self-reported depression is more common among women with obstructive sleep apnea (OSA) compared with men with OSA, but data on the relationship among depression, severity of OSA, and sleepiness are limited, said Dr. Stacey Ishman of Johns Hopkins University, Baltimore.

Dr. Ishman and her colleagues evaluated 56 consecutive OSA patients aged 27-74 years who presented to an otolaryngology clinic and compared them with 51 controls. The average age of patients and controls alike was 47 years. A total of 61% of the OSA patients were male.

Overall, significantly more OSA patients met the criteria for depression, compared with controls (29% vs. 8%). The severity of OSA (measured using the Respiratory Disturbance Index) was a significant predictor of Beck Depression Inventory (BDI) scores, but BDI scores were not correlated with the severity of OSA.

These findings suggest that “depression may be significant even in patients with mild OSA,” Dr. Ishman said at the meeting jointly sponsored by the Triological Society and the American College of Surgeons. BDI scores were significantly correlated with higher Epworth Sleepiness Scale (ESS) scores, but the ESS did not correlate with sleep apnea severity.

Disclosures: Dr. Ishman had no financial conflicts to disclose.

ORLANDO — Obstructive sleep apnea patients with symptoms of excessive sleepiness have the greatest risk of depression, based on data from a prospective study of 107 adults.

Data from previous studies have shown that self-reported depression is more common among women with obstructive sleep apnea (OSA) compared with men with OSA, but data on the relationship among depression, severity of OSA, and sleepiness are limited, said Dr. Stacey Ishman of Johns Hopkins University, Baltimore.

Dr. Ishman and her colleagues evaluated 56 consecutive OSA patients aged 27-74 years who presented to an otolaryngology clinic and compared them with 51 controls. The average age of patients and controls alike was 47 years. A total of 61% of the OSA patients were male.

Overall, significantly more OSA patients met the criteria for depression, compared with controls (29% vs. 8%). The severity of OSA (measured using the Respiratory Disturbance Index) was a significant predictor of Beck Depression Inventory (BDI) scores, but BDI scores were not correlated with the severity of OSA.

These findings suggest that “depression may be significant even in patients with mild OSA,” Dr. Ishman said at the meeting jointly sponsored by the Triological Society and the American College of Surgeons. BDI scores were significantly correlated with higher Epworth Sleepiness Scale (ESS) scores, but the ESS did not correlate with sleep apnea severity.

Disclosures: Dr. Ishman had no financial conflicts to disclose.

ORLANDO — Obstructive sleep apnea patients with symptoms of excessive sleepiness have the greatest risk of depression, based on data from a prospective study of 107 adults.

Data from previous studies have shown that self-reported depression is more common among women with obstructive sleep apnea (OSA) compared with men with OSA, but data on the relationship among depression, severity of OSA, and sleepiness are limited, said Dr. Stacey Ishman of Johns Hopkins University, Baltimore.

Dr. Ishman and her colleagues evaluated 56 consecutive OSA patients aged 27-74 years who presented to an otolaryngology clinic and compared them with 51 controls. The average age of patients and controls alike was 47 years. A total of 61% of the OSA patients were male.

Overall, significantly more OSA patients met the criteria for depression, compared with controls (29% vs. 8%). The severity of OSA (measured using the Respiratory Disturbance Index) was a significant predictor of Beck Depression Inventory (BDI) scores, but BDI scores were not correlated with the severity of OSA.

These findings suggest that “depression may be significant even in patients with mild OSA,” Dr. Ishman said at the meeting jointly sponsored by the Triological Society and the American College of Surgeons. BDI scores were significantly correlated with higher Epworth Sleepiness Scale (ESS) scores, but the ESS did not correlate with sleep apnea severity.

Disclosures: Dr. Ishman had no financial conflicts to disclose.

Major Finding: 29% of patients with OSA met criteria for depression, compared with 8% of controls.

Data Source: Prospective study of 56 obstructive sleep apnea patients at an otolaryngology clinic.

Disclosures: Dr. Ishman had no financial conflicts.

ORLANDO — Obstructive sleep apnea patients with symptoms of excessive sleepiness have the greatest risk of depression, based on data from a prospective study of 107 adults.

Data from previous studies have shown that self-reported depression is more common among women with obstructive sleep apnea (OSA) compared with men with OSA, but data on the relationship among depression, severity of OSA, and sleepiness are limited, said Dr. Stacey Ishman of Johns Hopkins University, Baltimore.

Dr. Ishman and her colleagues evaluated 56 consecutive OSA patients aged 27-74 years who presented to an otolaryngology clinic and compared them with 51 controls. The average age of patients and controls was 47 years; 61% of the OSA patients were male.

Overall, significantly more OSA patients met the criteria for depression, compared with controls (29% vs. 8%). The severity of OSA (measured using the Respiratory Disturbance Index) was a significant predictor of Beck Depression Inventory (BDI) scores, but BDI scores were not correlated with the severity of OSA.

These findings suggest that “depression may be significant even in patients with mild OSA,” Dr. Ishman said at the meeting jointly sponsored by the Triological Society and the American College of Surgeons.

BDI scores were significantly correlated with higher scores on the Epworth Sleepiness Scale (ESS), but the ESS did not correlate with the severity of sleep apnea. However, findings from previous studies have shown that more than 50% of individuals with severe OSA (an apnea-hypopnea index of at least 30 events/hour) do not report subjective sleepiness, she noted.

The relationship between BDI and ESS suggests that OSA patients with excessive sleepiness in particular might benefit from depression screening, she said.

Major Finding: 29% of patients with OSA met criteria for depression, compared with 8% of controls.

Data Source: Prospective study of 56 obstructive sleep apnea patients at an otolaryngology clinic.

Disclosures: Dr. Ishman had no financial conflicts.

ORLANDO — Obstructive sleep apnea patients with symptoms of excessive sleepiness have the greatest risk of depression, based on data from a prospective study of 107 adults.

Data from previous studies have shown that self-reported depression is more common among women with obstructive sleep apnea (OSA) compared with men with OSA, but data on the relationship among depression, severity of OSA, and sleepiness are limited, said Dr. Stacey Ishman of Johns Hopkins University, Baltimore.

Dr. Ishman and her colleagues evaluated 56 consecutive OSA patients aged 27-74 years who presented to an otolaryngology clinic and compared them with 51 controls. The average age of patients and controls was 47 years; 61% of the OSA patients were male.

Overall, significantly more OSA patients met the criteria for depression, compared with controls (29% vs. 8%). The severity of OSA (measured using the Respiratory Disturbance Index) was a significant predictor of Beck Depression Inventory (BDI) scores, but BDI scores were not correlated with the severity of OSA.

These findings suggest that “depression may be significant even in patients with mild OSA,” Dr. Ishman said at the meeting jointly sponsored by the Triological Society and the American College of Surgeons.

BDI scores were significantly correlated with higher scores on the Epworth Sleepiness Scale (ESS), but the ESS did not correlate with the severity of sleep apnea. However, findings from previous studies have shown that more than 50% of individuals with severe OSA (an apnea-hypopnea index of at least 30 events/hour) do not report subjective sleepiness, she noted.

The relationship between BDI and ESS suggests that OSA patients with excessive sleepiness in particular might benefit from depression screening, she said.

Major Finding: 29% of patients with OSA met criteria for depression, compared with 8% of controls.

Data Source: Prospective study of 56 obstructive sleep apnea patients at an otolaryngology clinic.

Disclosures: Dr. Ishman had no financial conflicts.

ORLANDO — Obstructive sleep apnea patients with symptoms of excessive sleepiness have the greatest risk of depression, based on data from a prospective study of 107 adults.

Data from previous studies have shown that self-reported depression is more common among women with obstructive sleep apnea (OSA) compared with men with OSA, but data on the relationship among depression, severity of OSA, and sleepiness are limited, said Dr. Stacey Ishman of Johns Hopkins University, Baltimore.

Dr. Ishman and her colleagues evaluated 56 consecutive OSA patients aged 27-74 years who presented to an otolaryngology clinic and compared them with 51 controls. The average age of patients and controls was 47 years; 61% of the OSA patients were male.

Overall, significantly more OSA patients met the criteria for depression, compared with controls (29% vs. 8%). The severity of OSA (measured using the Respiratory Disturbance Index) was a significant predictor of Beck Depression Inventory (BDI) scores, but BDI scores were not correlated with the severity of OSA.

These findings suggest that “depression may be significant even in patients with mild OSA,” Dr. Ishman said at the meeting jointly sponsored by the Triological Society and the American College of Surgeons.

BDI scores were significantly correlated with higher scores on the Epworth Sleepiness Scale (ESS), but the ESS did not correlate with the severity of sleep apnea. However, findings from previous studies have shown that more than 50% of individuals with severe OSA (an apnea-hypopnea index of at least 30 events/hour) do not report subjective sleepiness, she noted.

The relationship between BDI and ESS suggests that OSA patients with excessive sleepiness in particular might benefit from depression screening, she said.

Major Finding: The annualized relapse rate was reduced by 54% in multiple sclerosis patients who took 0.5 mg of fingolimod and by 60% in those who took 1.25 mg of fingolimod. After 24 months, around 70% of patients given fingolimod were relapse free, compared with 46% of the placebo group.

Data Source: A randomized, double-blind, placebo-controlled phase III study of 1,272 adults with MS.

Disclosures: The study was supported by Novartis Pharma AG. Dr. Kappos has received research support from multiple pharmaceutical companies, including Novartis. Dr. O'Connor has served as a consultant and received research support for multiple pharmaceutical companies, including Novartis.

TORONTO — The investigational drug fingolimod at doses of 0.5 mg and 1.25 mg appears to be a safe and effective treatment for adults with multiple sclerosis, based on data from more than 1,000 patients.

In previous studies, fingolimod had “a clear cut effect on inflammatory outcomes” in relapsing-remitting multiple sclerosis patients, said Dr. Ludwig Kappos of University Hospital in Basel, Switzerland.

The current phase III study addressed whether the effects of fingolimod (FTY720) persisted over time, and whether a 0.5-mg dose is as effective as the previously studied 1.25-mg dose. The main outcome was relapse rate per year over a 2-year follow-up period.

The Food and Drug Administration is scheduled to review the safety and efficacy data for fingolimod this month.

The Fingolimod (FTY720) vs. Placebo in Relapsing-Remitting Multiple Sclerosis (FREEDOMS) study included 1,272 patients aged 18-55 years.

The average age of the patients was 37 years, and the average duration of MS was 8 years.

Patients with systemic or immune system disease were excluded, and 1,033 patients completed the study.

Patients were randomized to receive a daily dose of 1.25 mg fingolimod, 0.5 mg fingolimod, or a placebo.

The annualized relapse rate was reduced by 54% in patients who took 0.5 mg of fingolimod and by 60% in those who took 1.25 mg of fingolimod.

There was no significant difference in effectiveness between the doses, and both doses were significantly more effective than the placebo.

After 24 months, significantly more patients in either fingolimod group (70%-75%) were relapse free, compared with 46% of the placebo group.

In addition, both the 1.25-mg and 0.5-mg doses of fingolimod were associated with of 32% and 30%, reductions, respectively, in the risk of 3-month confirmed disability progression. Both reductions were significant, compared with placebo.

Similarly, both the 1.25-mg and 0.5-mg doses were associated with reductions in risk of 6-month confirmed disability progression of 40% and 37%, also significant compared with placebo.

Safety and tolerability data for the study population were presented separately in a poster by Dr. Paul O'Connor of St. Michael's Hospital, Toronto, and his colleagues.

In the safety analysis, the researchers evaluated all patients at baseline screening, week 2, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24.

Overall, the incidence of any adverse event was 94% in both of the fingolimod groups and 93% in the placebo group. The incidence of an adverse event that caused a patient to stop treatment was 14% in the 1.25-mg group, and 8% in both the 0.5-mg and placebo groups.

Serious adverse events were reported in 51 patients (12%) in the 1.25-mg group, 42 patients (10%) in the 0.5-mg group, and 56 patients (13%) in the placebo group. Serious adverse events included cardiovascular disorders, neoplasms, nervous system disorders, macular edema, and abnormal liver function test results.

Sinus bradycardia, the most common ECG finding, occurred in 47 patients (11%) in the 1.25-mg group, 20 patients (5%) in the 0.5-mg group, and 6 patients (2%) in the placebo group.

In addition, first- and second-degree atrioventricular blocks were reported in 20 patients (5%) and 1 patient (0.2%), respectively, in the 0.5-mg group, compared with 37 patients (9%) and 4 patients (1%), respectively, in the 1.25-mg group.

Malignant neoplasms were reported in 4 patients in each of the fingolimod groups and in 10 patients in the placebo group.

All 11 cases of skin cancer reported in the study were successfully treated with excision.

Abnormal liver function tests were reported more than twice as frequently in the fingolimod 1.25-mg and 0.5-mg groups, compared with placebo (19%, 16%, and 5%, respectively).

But “liver enzyme elevations were asymptomatic and improved once therapy was discontinued; no patient developed liver failure,” the investigators wrote.

In the 1.25-mg group, one case of ischemic stroke occurred during the study period, and a transient ischemic attack occurred 8 months after the discontinuation of treatment.

No clinically relevant pulmonary function changes were observed in any of the groups.

All seven reported cases of macular edema occurred in the group that took 1.25 mg of fingolimod, and all cases resolved after treatment was discontinued.

The overall incidence of infections was similar (69%-72%) for all three groups, and included herpesvirus infections, lower respiratory tract infections, and urinary tract infections.

The results support safety data from previous studies and suggest that most patients with MS tolerate oral fingolimod, the researchers said.

Also consistent with previous studies, “the overall safety profile of fingolimod 0.5 mg appears to be more favorable than that of the 1.25-mg dose,” they added.

Major Finding: The annualized relapse rate was reduced by 54% in multiple sclerosis patients who took 0.5 mg of fingolimod and by 60% in those who took 1.25 mg of fingolimod. After 24 months, around 70% of patients given fingolimod were relapse free, compared with 46% of the placebo group.

Data Source: A randomized, double-blind, placebo-controlled phase III study of 1,272 adults with MS.

Disclosures: The study was supported by Novartis Pharma AG. Dr. Kappos has received research support from multiple pharmaceutical companies, including Novartis. Dr. O'Connor has served as a consultant and received research support for multiple pharmaceutical companies, including Novartis.

TORONTO — The investigational drug fingolimod at doses of 0.5 mg and 1.25 mg appears to be a safe and effective treatment for adults with multiple sclerosis, based on data from more than 1,000 patients.

In previous studies, fingolimod had “a clear cut effect on inflammatory outcomes” in relapsing-remitting multiple sclerosis patients, said Dr. Ludwig Kappos of University Hospital in Basel, Switzerland.

The current phase III study addressed whether the effects of fingolimod (FTY720) persisted over time, and whether a 0.5-mg dose is as effective as the previously studied 1.25-mg dose. The main outcome was relapse rate per year over a 2-year follow-up period.

The Food and Drug Administration is scheduled to review the safety and efficacy data for fingolimod this month.

The Fingolimod (FTY720) vs. Placebo in Relapsing-Remitting Multiple Sclerosis (FREEDOMS) study included 1,272 patients aged 18-55 years.

The average age of the patients was 37 years, and the average duration of MS was 8 years.

Patients with systemic or immune system disease were excluded, and 1,033 patients completed the study.

Patients were randomized to receive a daily dose of 1.25 mg fingolimod, 0.5 mg fingolimod, or a placebo.

The annualized relapse rate was reduced by 54% in patients who took 0.5 mg of fingolimod and by 60% in those who took 1.25 mg of fingolimod.

There was no significant difference in effectiveness between the doses, and both doses were significantly more effective than the placebo.

After 24 months, significantly more patients in either fingolimod group (70%-75%) were relapse free, compared with 46% of the placebo group.

In addition, both the 1.25-mg and 0.5-mg doses of fingolimod were associated with of 32% and 30%, reductions, respectively, in the risk of 3-month confirmed disability progression. Both reductions were significant, compared with placebo.

Similarly, both the 1.25-mg and 0.5-mg doses were associated with reductions in risk of 6-month confirmed disability progression of 40% and 37%, also significant compared with placebo.

Safety and tolerability data for the study population were presented separately in a poster by Dr. Paul O'Connor of St. Michael's Hospital, Toronto, and his colleagues.

In the safety analysis, the researchers evaluated all patients at baseline screening, week 2, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24.

Overall, the incidence of any adverse event was 94% in both of the fingolimod groups and 93% in the placebo group. The incidence of an adverse event that caused a patient to stop treatment was 14% in the 1.25-mg group, and 8% in both the 0.5-mg and placebo groups.

Serious adverse events were reported in 51 patients (12%) in the 1.25-mg group, 42 patients (10%) in the 0.5-mg group, and 56 patients (13%) in the placebo group. Serious adverse events included cardiovascular disorders, neoplasms, nervous system disorders, macular edema, and abnormal liver function test results.

Sinus bradycardia, the most common ECG finding, occurred in 47 patients (11%) in the 1.25-mg group, 20 patients (5%) in the 0.5-mg group, and 6 patients (2%) in the placebo group.

In addition, first- and second-degree atrioventricular blocks were reported in 20 patients (5%) and 1 patient (0.2%), respectively, in the 0.5-mg group, compared with 37 patients (9%) and 4 patients (1%), respectively, in the 1.25-mg group.

Malignant neoplasms were reported in 4 patients in each of the fingolimod groups and in 10 patients in the placebo group.

All 11 cases of skin cancer reported in the study were successfully treated with excision.

Abnormal liver function tests were reported more than twice as frequently in the fingolimod 1.25-mg and 0.5-mg groups, compared with placebo (19%, 16%, and 5%, respectively).

But “liver enzyme elevations were asymptomatic and improved once therapy was discontinued; no patient developed liver failure,” the investigators wrote.

In the 1.25-mg group, one case of ischemic stroke occurred during the study period, and a transient ischemic attack occurred 8 months after the discontinuation of treatment.

No clinically relevant pulmonary function changes were observed in any of the groups.

All seven reported cases of macular edema occurred in the group that took 1.25 mg of fingolimod, and all cases resolved after treatment was discontinued.

The overall incidence of infections was similar (69%-72%) for all three groups, and included herpesvirus infections, lower respiratory tract infections, and urinary tract infections.

The results support safety data from previous studies and suggest that most patients with MS tolerate oral fingolimod, the researchers said.

Also consistent with previous studies, “the overall safety profile of fingolimod 0.5 mg appears to be more favorable than that of the 1.25-mg dose,” they added.

Major Finding: The annualized relapse rate was reduced by 54% in multiple sclerosis patients who took 0.5 mg of fingolimod and by 60% in those who took 1.25 mg of fingolimod. After 24 months, around 70% of patients given fingolimod were relapse free, compared with 46% of the placebo group.

Data Source: A randomized, double-blind, placebo-controlled phase III study of 1,272 adults with MS.

Disclosures: The study was supported by Novartis Pharma AG. Dr. Kappos has received research support from multiple pharmaceutical companies, including Novartis. Dr. O'Connor has served as a consultant and received research support for multiple pharmaceutical companies, including Novartis.

TORONTO — The investigational drug fingolimod at doses of 0.5 mg and 1.25 mg appears to be a safe and effective treatment for adults with multiple sclerosis, based on data from more than 1,000 patients.

In previous studies, fingolimod had “a clear cut effect on inflammatory outcomes” in relapsing-remitting multiple sclerosis patients, said Dr. Ludwig Kappos of University Hospital in Basel, Switzerland.

The current phase III study addressed whether the effects of fingolimod (FTY720) persisted over time, and whether a 0.5-mg dose is as effective as the previously studied 1.25-mg dose. The main outcome was relapse rate per year over a 2-year follow-up period.

The Food and Drug Administration is scheduled to review the safety and efficacy data for fingolimod this month.

The Fingolimod (FTY720) vs. Placebo in Relapsing-Remitting Multiple Sclerosis (FREEDOMS) study included 1,272 patients aged 18-55 years.

The average age of the patients was 37 years, and the average duration of MS was 8 years.

Patients with systemic or immune system disease were excluded, and 1,033 patients completed the study.

Patients were randomized to receive a daily dose of 1.25 mg fingolimod, 0.5 mg fingolimod, or a placebo.

The annualized relapse rate was reduced by 54% in patients who took 0.5 mg of fingolimod and by 60% in those who took 1.25 mg of fingolimod.

There was no significant difference in effectiveness between the doses, and both doses were significantly more effective than the placebo.

After 24 months, significantly more patients in either fingolimod group (70%-75%) were relapse free, compared with 46% of the placebo group.

In addition, both the 1.25-mg and 0.5-mg doses of fingolimod were associated with of 32% and 30%, reductions, respectively, in the risk of 3-month confirmed disability progression. Both reductions were significant, compared with placebo.

Similarly, both the 1.25-mg and 0.5-mg doses were associated with reductions in risk of 6-month confirmed disability progression of 40% and 37%, also significant compared with placebo.

Safety and tolerability data for the study population were presented separately in a poster by Dr. Paul O'Connor of St. Michael's Hospital, Toronto, and his colleagues.

In the safety analysis, the researchers evaluated all patients at baseline screening, week 2, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24.

Overall, the incidence of any adverse event was 94% in both of the fingolimod groups and 93% in the placebo group. The incidence of an adverse event that caused a patient to stop treatment was 14% in the 1.25-mg group, and 8% in both the 0.5-mg and placebo groups.

Serious adverse events were reported in 51 patients (12%) in the 1.25-mg group, 42 patients (10%) in the 0.5-mg group, and 56 patients (13%) in the placebo group. Serious adverse events included cardiovascular disorders, neoplasms, nervous system disorders, macular edema, and abnormal liver function test results.

Sinus bradycardia, the most common ECG finding, occurred in 47 patients (11%) in the 1.25-mg group, 20 patients (5%) in the 0.5-mg group, and 6 patients (2%) in the placebo group.

In addition, first- and second-degree atrioventricular blocks were reported in 20 patients (5%) and 1 patient (0.2%), respectively, in the 0.5-mg group, compared with 37 patients (9%) and 4 patients (1%), respectively, in the 1.25-mg group.

Malignant neoplasms were reported in 4 patients in each of the fingolimod groups and in 10 patients in the placebo group.

All 11 cases of skin cancer reported in the study were successfully treated with excision.

Abnormal liver function tests were reported more than twice as frequently in the fingolimod 1.25-mg and 0.5-mg groups, compared with placebo (19%, 16%, and 5%, respectively).

But “liver enzyme elevations were asymptomatic and improved once therapy was discontinued; no patient developed liver failure,” the investigators wrote.

In the 1.25-mg group, one case of ischemic stroke occurred during the study period, and a transient ischemic attack occurred 8 months after the discontinuation of treatment.

No clinically relevant pulmonary function changes were observed in any of the groups.

All seven reported cases of macular edema occurred in the group that took 1.25 mg of fingolimod, and all cases resolved after treatment was discontinued.

The overall incidence of infections was similar (69%-72%) for all three groups, and included herpesvirus infections, lower respiratory tract infections, and urinary tract infections.

The results support safety data from previous studies and suggest that most patients with MS tolerate oral fingolimod, the researchers said.

Also consistent with previous studies, “the overall safety profile of fingolimod 0.5 mg appears to be more favorable than that of the 1.25-mg dose,” they added.

TORONTO — About 40% of epilepsy patients are bothered by side effects of their antiepileptic drugs, based on data from a survey of adults with epilepsy.

Information on the tolerability of antiepileptic drugs (AEDs) and the reasons for discontinuing treatment are limited, George J. Wan, Ph.D., said in a poster.

To examine drug tolerability and treatment satisfaction, Dr. Wan and his colleagues reviewed data from the National Survey of Epilepsy, Comorbidities, and Health Outcomes (EPIC), a large U.S. survey conducted in 2009 that included 7,500 epilepsy patients and 2,500 controls.

A total of 2,395 respondents reported being formally diagnosed with epilepsy or a seizure disorder; of those, 1,415 (59%) were taking antiepilepsy drugs at the time of the survey. About 60% of the respondents reported taking one AED, 35% reported taking two or three, and 5% reported taking four or more.

A total of 772 respondents said that they were “not at all” bothered by side effects from AEDs. But 519 respondents reported some degree of bother: 22% were mildly bothered; 12%, moderately bothered; 5%, markedly bothered; and 1%, extremely bothered. The researchers did not identify specific side effects.

Overall, 72% of the respondents said they were either “somewhat satisfied” or “very satisfied” with their current AED regimens. But 304 respondents said that they had discontinued their medications. Of those, 50% discontinued on their doctor's advice; 45% because of side effects; 30% because of improvement in seizures; and 21% because of inadequate seizure control. Some respondents indicated more than one reason for discontinuing their AEDs.

Patients taking two or more AEDs were significantly more likely to be bothered by side effects, compared with those taking one, the researchers reported.

Disclosures: Dr. Wan is an employee of Ortho-McNeil Janssen Scientific Affairs, which supported the study.

TORONTO — About 40% of epilepsy patients are bothered by side effects of their antiepileptic drugs, based on data from a survey of adults with epilepsy.

Information on the tolerability of antiepileptic drugs (AEDs) and the reasons for discontinuing treatment are limited, George J. Wan, Ph.D., said in a poster.

To examine drug tolerability and treatment satisfaction, Dr. Wan and his colleagues reviewed data from the National Survey of Epilepsy, Comorbidities, and Health Outcomes (EPIC), a large U.S. survey conducted in 2009 that included 7,500 epilepsy patients and 2,500 controls.

A total of 2,395 respondents reported being formally diagnosed with epilepsy or a seizure disorder; of those, 1,415 (59%) were taking antiepilepsy drugs at the time of the survey. About 60% of the respondents reported taking one AED, 35% reported taking two or three, and 5% reported taking four or more.

A total of 772 respondents said that they were “not at all” bothered by side effects from AEDs. But 519 respondents reported some degree of bother: 22% were mildly bothered; 12%, moderately bothered; 5%, markedly bothered; and 1%, extremely bothered. The researchers did not identify specific side effects.

Overall, 72% of the respondents said they were either “somewhat satisfied” or “very satisfied” with their current AED regimens. But 304 respondents said that they had discontinued their medications. Of those, 50% discontinued on their doctor's advice; 45% because of side effects; 30% because of improvement in seizures; and 21% because of inadequate seizure control. Some respondents indicated more than one reason for discontinuing their AEDs.

Patients taking two or more AEDs were significantly more likely to be bothered by side effects, compared with those taking one, the researchers reported.

Disclosures: Dr. Wan is an employee of Ortho-McNeil Janssen Scientific Affairs, which supported the study.

TORONTO — About 40% of epilepsy patients are bothered by side effects of their antiepileptic drugs, based on data from a survey of adults with epilepsy.

Information on the tolerability of antiepileptic drugs (AEDs) and the reasons for discontinuing treatment are limited, George J. Wan, Ph.D., said in a poster.

To examine drug tolerability and treatment satisfaction, Dr. Wan and his colleagues reviewed data from the National Survey of Epilepsy, Comorbidities, and Health Outcomes (EPIC), a large U.S. survey conducted in 2009 that included 7,500 epilepsy patients and 2,500 controls.

A total of 2,395 respondents reported being formally diagnosed with epilepsy or a seizure disorder; of those, 1,415 (59%) were taking antiepilepsy drugs at the time of the survey. About 60% of the respondents reported taking one AED, 35% reported taking two or three, and 5% reported taking four or more.

A total of 772 respondents said that they were “not at all” bothered by side effects from AEDs. But 519 respondents reported some degree of bother: 22% were mildly bothered; 12%, moderately bothered; 5%, markedly bothered; and 1%, extremely bothered. The researchers did not identify specific side effects.

Overall, 72% of the respondents said they were either “somewhat satisfied” or “very satisfied” with their current AED regimens. But 304 respondents said that they had discontinued their medications. Of those, 50% discontinued on their doctor's advice; 45% because of side effects; 30% because of improvement in seizures; and 21% because of inadequate seizure control. Some respondents indicated more than one reason for discontinuing their AEDs.

Patients taking two or more AEDs were significantly more likely to be bothered by side effects, compared with those taking one, the researchers reported.

Disclosures: Dr. Wan is an employee of Ortho-McNeil Janssen Scientific Affairs, which supported the study.

Indoor tanning is associated with a fourfold increased risk of melanoma, according to findings published online May 27 in Cancer Epidemiology, Biomarkers & Prevention.

The findings were based on data from the Skin Health Study, a population-based, case-control study of 1,167 cases and 1,101 controls.

Photo copyright: Bora Ucak/iStockphoto.com

Melanoma was 2.9 times more likely to occur in users of high-speed/high-intensity (UVB-enhanced) tanning devices and 4.4 times more likely in users of high-pressure (primarily UVA-emitting) devices, compared with individuals who had never used the devices.

In addition, melanoma was 1.8 and 1.9 times more likely in users of conventional indoor tanning devices and sunlamps, respectively, compared with never users.

The study population included individuals aged 25-59 years who were diagnosed with invasive cutaneous melanoma between July 2004 and December 2007 in Minnesota and who were enrolled in a state cancer registry. Controls were selected at random from the Minnesota state driver’s license list. Study participants completed a self-administered questionnaire and a detailed 1-hour phone interview (Cancer Epidemiol. Biomarkers Prev. 2010 [doi: 10.1158/1055-9965.EPI-09-1249]).

DeAnn Lazovich, Ph.D., of the University of Minnesota, Minneapolis, and colleagues began the Skin Health Study in 2004 in Minnesota, a state with a documented high rate of indoor tanning. The data collected by the researchers included skin, hair, and eye color; presence of moles and freckles; lifetime routine sun exposure; age at which tanning beds were first used; duration and frequency of indoor tanning; and type of tanning device used.

Overall, 63% of individuals with melanoma and 51% of controls reported any indoor tanning. Melanoma risk increased significantly as the frequency of indoor tanning increased. Individuals with melanoma were more than twice as likely as controls to report painful burns resulting from indoor tanning, and they reported significantly more of these painful burns than controls.

The researchers also noted that a dose-response relationship between the number of tanning sessions and the number of melanoma lesions on the trunk was identified in both men and women.

“We did not find lifetime routine sun exposure or sun exposure via recreational outdoor activities or occupations to be associated with melanoma risk,” Dr. Lazovich and associates wrote. “To the extent that sunburns are a marker of intermittent sun exposure, then our results adequately represent the independent effect of indoor tanning use on the risk of melanoma.”

“As dermatologists, we see the horrible price paid for using these devices,” Dr. Allan C. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York, said during a teleconference on May 27 to discuss the study findings. Dr. Halpern was not involved in the study.

“We now know that the total amount of UV exposure in tanning beds over time is important,” Dr. Halpern said. “I’m hopeful that this study is going to be very helpful in the hands of the FDA to further regulate the industry.” 

Dr. Halpern said that dermatologists have long understood the importance of educating patients about the dangers of indoor tanning devices, but that misinformation about the risks and benefits of indoor tanning persist.

 “I think this study very much strengthens our hand,” he said. Dr. Halpern added that he was encouraged to see the consumer video posted by the FDA earlier this week, which states than any UV indoor tanning device should be avoided.

In 2009, the International Agency for Research on Cancer classified tanning beds as carcinogenic to humans. In 2010, a Food and Drug Administration advisory panel recommended tighter restrictions on the use of indoor tanning devices, but the FDA has yet to issue any guidelines based on these recommendations.

The findings address several limitations of previous studies on this topic, including the ability to control for confounding variables such as sun exposure, the investigators noted.

None of the study authors stated that they had any conflicts of interest to disclose. The study was supported in part by a grant from the American Cancer Society and the National Cancer Institute.

Indoor tanning is associated with a fourfold increased risk of melanoma, according to findings published online May 27 in Cancer Epidemiology, Biomarkers & Prevention.

The findings were based on data from the Skin Health Study, a population-based, case-control study of 1,167 cases and 1,101 controls.

Photo copyright: Bora Ucak/iStockphoto.com

Melanoma was 2.9 times more likely to occur in users of high-speed/high-intensity (UVB-enhanced) tanning devices and 4.4 times more likely in users of high-pressure (primarily UVA-emitting) devices, compared with individuals who had never used the devices.

In addition, melanoma was 1.8 and 1.9 times more likely in users of conventional indoor tanning devices and sunlamps, respectively, compared with never users.

The study population included individuals aged 25-59 years who were diagnosed with invasive cutaneous melanoma between July 2004 and December 2007 in Minnesota and who were enrolled in a state cancer registry. Controls were selected at random from the Minnesota state driver’s license list. Study participants completed a self-administered questionnaire and a detailed 1-hour phone interview (Cancer Epidemiol. Biomarkers Prev. 2010 [doi: 10.1158/1055-9965.EPI-09-1249]).

DeAnn Lazovich, Ph.D., of the University of Minnesota, Minneapolis, and colleagues began the Skin Health Study in 2004 in Minnesota, a state with a documented high rate of indoor tanning. The data collected by the researchers included skin, hair, and eye color; presence of moles and freckles; lifetime routine sun exposure; age at which tanning beds were first used; duration and frequency of indoor tanning; and type of tanning device used.

Overall, 63% of individuals with melanoma and 51% of controls reported any indoor tanning. Melanoma risk increased significantly as the frequency of indoor tanning increased. Individuals with melanoma were more than twice as likely as controls to report painful burns resulting from indoor tanning, and they reported significantly more of these painful burns than controls.

The researchers also noted that a dose-response relationship between the number of tanning sessions and the number of melanoma lesions on the trunk was identified in both men and women.

“We did not find lifetime routine sun exposure or sun exposure via recreational outdoor activities or occupations to be associated with melanoma risk,” Dr. Lazovich and associates wrote. “To the extent that sunburns are a marker of intermittent sun exposure, then our results adequately represent the independent effect of indoor tanning use on the risk of melanoma.”

“As dermatologists, we see the horrible price paid for using these devices,” Dr. Allan C. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York, said during a teleconference on May 27 to discuss the study findings. Dr. Halpern was not involved in the study.

“We now know that the total amount of UV exposure in tanning beds over time is important,” Dr. Halpern said. “I’m hopeful that this study is going to be very helpful in the hands of the FDA to further regulate the industry.” 

Dr. Halpern said that dermatologists have long understood the importance of educating patients about the dangers of indoor tanning devices, but that misinformation about the risks and benefits of indoor tanning persist.

 “I think this study very much strengthens our hand,” he said. Dr. Halpern added that he was encouraged to see the consumer video posted by the FDA earlier this week, which states than any UV indoor tanning device should be avoided.

In 2009, the International Agency for Research on Cancer classified tanning beds as carcinogenic to humans. In 2010, a Food and Drug Administration advisory panel recommended tighter restrictions on the use of indoor tanning devices, but the FDA has yet to issue any guidelines based on these recommendations.

The findings address several limitations of previous studies on this topic, including the ability to control for confounding variables such as sun exposure, the investigators noted.

None of the study authors stated that they had any conflicts of interest to disclose. The study was supported in part by a grant from the American Cancer Society and the National Cancer Institute.

Indoor tanning is associated with a fourfold increased risk of melanoma, according to findings published online May 27 in Cancer Epidemiology, Biomarkers & Prevention.

The findings were based on data from the Skin Health Study, a population-based, case-control study of 1,167 cases and 1,101 controls.

Photo copyright: Bora Ucak/iStockphoto.com

Melanoma was 2.9 times more likely to occur in users of high-speed/high-intensity (UVB-enhanced) tanning devices and 4.4 times more likely in users of high-pressure (primarily UVA-emitting) devices, compared with individuals who had never used the devices.

In addition, melanoma was 1.8 and 1.9 times more likely in users of conventional indoor tanning devices and sunlamps, respectively, compared with never users.

The study population included individuals aged 25-59 years who were diagnosed with invasive cutaneous melanoma between July 2004 and December 2007 in Minnesota and who were enrolled in a state cancer registry. Controls were selected at random from the Minnesota state driver’s license list. Study participants completed a self-administered questionnaire and a detailed 1-hour phone interview (Cancer Epidemiol. Biomarkers Prev. 2010 [doi: 10.1158/1055-9965.EPI-09-1249]).

DeAnn Lazovich, Ph.D., of the University of Minnesota, Minneapolis, and colleagues began the Skin Health Study in 2004 in Minnesota, a state with a documented high rate of indoor tanning. The data collected by the researchers included skin, hair, and eye color; presence of moles and freckles; lifetime routine sun exposure; age at which tanning beds were first used; duration and frequency of indoor tanning; and type of tanning device used.

Overall, 63% of individuals with melanoma and 51% of controls reported any indoor tanning. Melanoma risk increased significantly as the frequency of indoor tanning increased. Individuals with melanoma were more than twice as likely as controls to report painful burns resulting from indoor tanning, and they reported significantly more of these painful burns than controls.

The researchers also noted that a dose-response relationship between the number of tanning sessions and the number of melanoma lesions on the trunk was identified in both men and women.

“We did not find lifetime routine sun exposure or sun exposure via recreational outdoor activities or occupations to be associated with melanoma risk,” Dr. Lazovich and associates wrote. “To the extent that sunburns are a marker of intermittent sun exposure, then our results adequately represent the independent effect of indoor tanning use on the risk of melanoma.”

“As dermatologists, we see the horrible price paid for using these devices,” Dr. Allan C. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York, said during a teleconference on May 27 to discuss the study findings. Dr. Halpern was not involved in the study.

“We now know that the total amount of UV exposure in tanning beds over time is important,” Dr. Halpern said. “I’m hopeful that this study is going to be very helpful in the hands of the FDA to further regulate the industry.” 

Dr. Halpern said that dermatologists have long understood the importance of educating patients about the dangers of indoor tanning devices, but that misinformation about the risks and benefits of indoor tanning persist.

 “I think this study very much strengthens our hand,” he said. Dr. Halpern added that he was encouraged to see the consumer video posted by the FDA earlier this week, which states than any UV indoor tanning device should be avoided.

In 2009, the International Agency for Research on Cancer classified tanning beds as carcinogenic to humans. In 2010, a Food and Drug Administration advisory panel recommended tighter restrictions on the use of indoor tanning devices, but the FDA has yet to issue any guidelines based on these recommendations.

The findings address several limitations of previous studies on this topic, including the ability to control for confounding variables such as sun exposure, the investigators noted.

None of the study authors stated that they had any conflicts of interest to disclose. The study was supported in part by a grant from the American Cancer Society and the National Cancer Institute.