Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.

Kenishirotie/Thinkstock

According to new research, the costs of oral and injectable brand-name drugs increased annually during 2008-2016 by 9.2% and 15.1%, respectively, largely driven by existing drug prices.

For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.

Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.

“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.

“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.

“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.

Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.

The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.

“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”

The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.

The authors provided no disclosures.
 

gtwachtman@mdedge.com

SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.

Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.

Kenishirotie/Thinkstock

According to new research, the costs of oral and injectable brand-name drugs increased annually during 2008-2016 by 9.2% and 15.1%, respectively, largely driven by existing drug prices.

For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.

Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.

“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.

“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.

“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.

Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.

The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.

“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”

The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.

The authors provided no disclosures.
 

gtwachtman@mdedge.com

SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.

Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.

Kenishirotie/Thinkstock

According to new research, the costs of oral and injectable brand-name drugs increased annually during 2008-2016 by 9.2% and 15.1%, respectively, largely driven by existing drug prices.

For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.

Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.

“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.

“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.

“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.

Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.

The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.

“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”

The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.

The authors provided no disclosures.
 

gtwachtman@mdedge.com

SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

In this special edition of the MDedge Daily News, Nick Andrews and Terry Rudd report the latest news from the 2018 San Antonio Breast Cancer Symposium. Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.

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Apple Podcasts
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Spotify
 

In this special edition of the MDedge Daily News, Nick Andrews and Terry Rudd report the latest news from the 2018 San Antonio Breast Cancer Symposium. Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

In this special edition of the MDedge Daily News, Nick Andrews and Terry Rudd report the latest news from the 2018 San Antonio Breast Cancer Symposium. Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.

copyright Martynasfoto/Thinkstock

“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.

The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.

Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10^-25) and 4 weeks (P = 4.9 x 10^-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).

The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”

The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.

The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.

SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.

A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.

copyright Martynasfoto/Thinkstock

“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.

The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.

Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10^-25) and 4 weeks (P = 4.9 x 10^-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).

The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”

The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.

The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.

SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.

A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.

copyright Martynasfoto/Thinkstock

“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.

The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.

Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10^-25) and 4 weeks (P = 4.9 x 10^-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).

The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”

The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.

The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.

SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.

Ducray Densiage Redensifying Hair Care to Launch in March

Ducray Laboratoires Dermatologiques introduces the Densiage Redensifying hair care line for patients with thin and brittle hair. This line consists of 4 products: the Densiage Redensifying Shampoo to noticeably improve hair quality; the Densiage Redensifying Conditioner to provide detangling benefits and leave hair softer; the Densiage Redensifying Serum to promote development of thicker denser hair with more volume; and the Densiage Dietary Supplement for Aging Hair to provide nutrients to maintain hair density and protect against signs of aging. The line will be available in March 2019. For more information, visit www.ducray.com.

Revance Announces Phase 3 Results for Neuromodulator DaxibotulinumtoxinA

Revance Therapeutics, Inc, works to submit a Biologics License Application with the US Food and Drug Administration in the first half of 2019 for its injectable neuromodulator  axibotulinumtoxinA (RT002) following results from a phase 3 open-label, longterm safety study on treating moderate to severe glabellar (frown) lines. Participants received up to 3 treatments of RT002 and were followed for more than 1.5 years. Overall, the safety findings were consistent with the known safety profiles for currently available neuromodulators in aesthetics. Measuring duration of effect, the median time to return to baseline glabellar line severity was 28 weeks. The median time to loss of none or mild wrinkle severity was 24 weeks. The results demonstrate that RT002, utilizing proprietary stabilizing excipient peptide technology in its formulation, produces long duration and high response rates and is well tolerated over successive treatments. For more information, visit www.revance.com.

SNA-120 Demonstrates Potential for Psoriasis in Phase 2b Trial

Sienna Biopharmaceuticals announces results of a phase 2b study of the tropomyosin receptor kinase A (TrkA) inhibitor SNA-120 (pegcantratinib) for mild to moderate psoriasis, with itch as the primary end point. SNA-120 blocks nerve growth factor signaling, which plays an important role in the pathogenesis of psoriasis and itch. Participants (N=208) achieved 58% improvement in itch from baseline; efficacy results indicated 75% reduction in psoriasis area and severity index score from baseline in 27% of participants versus 13% with vehicle, and 29% of participants achieved 2-grade improvement in investigator global assessment versus 13% with vehicle. These results demonstrate the potential of SNA-120 as a topical nonsteroidal treatment of psoriasis. Phase 3 studies for psoriasis will begin in the second half of 2019. For more information, visit www.siennabio.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.

Ducray Densiage Redensifying Hair Care to Launch in March

Ducray Laboratoires Dermatologiques introduces the Densiage Redensifying hair care line for patients with thin and brittle hair. This line consists of 4 products: the Densiage Redensifying Shampoo to noticeably improve hair quality; the Densiage Redensifying Conditioner to provide detangling benefits and leave hair softer; the Densiage Redensifying Serum to promote development of thicker denser hair with more volume; and the Densiage Dietary Supplement for Aging Hair to provide nutrients to maintain hair density and protect against signs of aging. The line will be available in March 2019. For more information, visit www.ducray.com.

Revance Announces Phase 3 Results for Neuromodulator DaxibotulinumtoxinA

Revance Therapeutics, Inc, works to submit a Biologics License Application with the US Food and Drug Administration in the first half of 2019 for its injectable neuromodulator  axibotulinumtoxinA (RT002) following results from a phase 3 open-label, longterm safety study on treating moderate to severe glabellar (frown) lines. Participants received up to 3 treatments of RT002 and were followed for more than 1.5 years. Overall, the safety findings were consistent with the known safety profiles for currently available neuromodulators in aesthetics. Measuring duration of effect, the median time to return to baseline glabellar line severity was 28 weeks. The median time to loss of none or mild wrinkle severity was 24 weeks. The results demonstrate that RT002, utilizing proprietary stabilizing excipient peptide technology in its formulation, produces long duration and high response rates and is well tolerated over successive treatments. For more information, visit www.revance.com.

SNA-120 Demonstrates Potential for Psoriasis in Phase 2b Trial

Sienna Biopharmaceuticals announces results of a phase 2b study of the tropomyosin receptor kinase A (TrkA) inhibitor SNA-120 (pegcantratinib) for mild to moderate psoriasis, with itch as the primary end point. SNA-120 blocks nerve growth factor signaling, which plays an important role in the pathogenesis of psoriasis and itch. Participants (N=208) achieved 58% improvement in itch from baseline; efficacy results indicated 75% reduction in psoriasis area and severity index score from baseline in 27% of participants versus 13% with vehicle, and 29% of participants achieved 2-grade improvement in investigator global assessment versus 13% with vehicle. These results demonstrate the potential of SNA-120 as a topical nonsteroidal treatment of psoriasis. Phase 3 studies for psoriasis will begin in the second half of 2019. For more information, visit www.siennabio.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.

Ducray Densiage Redensifying Hair Care to Launch in March

Ducray Laboratoires Dermatologiques introduces the Densiage Redensifying hair care line for patients with thin and brittle hair. This line consists of 4 products: the Densiage Redensifying Shampoo to noticeably improve hair quality; the Densiage Redensifying Conditioner to provide detangling benefits and leave hair softer; the Densiage Redensifying Serum to promote development of thicker denser hair with more volume; and the Densiage Dietary Supplement for Aging Hair to provide nutrients to maintain hair density and protect against signs of aging. The line will be available in March 2019. For more information, visit www.ducray.com.

Revance Announces Phase 3 Results for Neuromodulator DaxibotulinumtoxinA

Revance Therapeutics, Inc, works to submit a Biologics License Application with the US Food and Drug Administration in the first half of 2019 for its injectable neuromodulator  axibotulinumtoxinA (RT002) following results from a phase 3 open-label, longterm safety study on treating moderate to severe glabellar (frown) lines. Participants received up to 3 treatments of RT002 and were followed for more than 1.5 years. Overall, the safety findings were consistent with the known safety profiles for currently available neuromodulators in aesthetics. Measuring duration of effect, the median time to return to baseline glabellar line severity was 28 weeks. The median time to loss of none or mild wrinkle severity was 24 weeks. The results demonstrate that RT002, utilizing proprietary stabilizing excipient peptide technology in its formulation, produces long duration and high response rates and is well tolerated over successive treatments. For more information, visit www.revance.com.

SNA-120 Demonstrates Potential for Psoriasis in Phase 2b Trial

Sienna Biopharmaceuticals announces results of a phase 2b study of the tropomyosin receptor kinase A (TrkA) inhibitor SNA-120 (pegcantratinib) for mild to moderate psoriasis, with itch as the primary end point. SNA-120 blocks nerve growth factor signaling, which plays an important role in the pathogenesis of psoriasis and itch. Participants (N=208) achieved 58% improvement in itch from baseline; efficacy results indicated 75% reduction in psoriasis area and severity index score from baseline in 27% of participants versus 13% with vehicle, and 29% of participants achieved 2-grade improvement in investigator global assessment versus 13% with vehicle. These results demonstrate the potential of SNA-120 as a topical nonsteroidal treatment of psoriasis. Phase 3 studies for psoriasis will begin in the second half of 2019. For more information, visit www.siennabio.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.

NEW ORLEANS – The population-level rate of sudden unexpected death in epilepsy (SUDEP) may have decreased over time, according to data described at the annual meeting of the American Epilepsy Society. Whether this decrease resulted from an improved understanding of SUDEP risk or a focus on risk-reduction strategies is unknown, said Daniel Friedman, MD, associate professor of neurology at the New York University Langone Health.

In addition, the rates of SUDEP in various populations differ according to their socioeconomic status. Differences in access to care are a potential, but unconfirmed, explanation for this association, said Dr. Friedman. Another possible explanation is that confounders such as mental health disorders, substance abuse, and insufficient social support affect individuals’ ability to manage their disorder.

Dr. Friedman and colleagues initially examined SUDEP rates over time in a cohort of patients who received vagus nerve stimulator (VNS) implantation for drug-resistant epilepsy. They analyzed data for 40,443 patients who underwent surgery during 1988-2012. The age-adjusted SUDEP rate per 1,000 person-years of follow-up decreased significantly from 2.47 in years 1-2 to 1.68 in years 3-10. “There was no control group, so we couldn’t necessarily attribute the SUDEP rate reduction to the intervention,” said Dr. Friedman. A study by Tomson et al of patients with epilepsy who received VNS implantation had similar findings.

The literature about the mechanisms of SUDEP and reduction of SUDEP risk has increased in recent years. Neurologists have advocated for greater disclosure to patients of SUDEP risk, as well as better risk counseling. Dr. Friedman and his colleagues decided to investigate whether these factors have affected the risk of SUDEP during the past decade.

They retrospectively examined data for people whose deaths had been investigated at medical examiner’s offices in New York City, San Diego County, and Maryland. They focused on decedents for whom epilepsy or seizure was listed as a cause or contributor to death or as a comorbid condition on the death certificate. They reviewed all available reports, including investigator notes, autopsy reports, and medical records. Next, Dr. Friedman and his colleagues calculated the annual SUDEP rate as a proportion of the general population, estimated using annual Census and American Community Survey data. They used the Mann-Kendall test to analyze the trends in SUDEP rate during 2009-2015.

Of 1,466 deaths in people with epilepsy during this period, 1,124 were classified as definite SUDEP, probable SUDEP, or near SUDEP. Approximately 63% of SUDEP cases were male, and 45% were African-American. The mean age at death was 38 years.

Dr. Friedman’s group found a significant decrease in the overall incidence of SUDEP in the total population during 2009-2015. When they examined the three regions separately, they found decreases in SUDEP incidence in New York City and Maryland, but not in San Diego County. They found no difference in SUDEP rates by season or by day of the week.

In a subsequent analysis, Dr. Friedman and his colleagues adjudicated all deaths related to seizure and epilepsy in the three regions during 2009-2010 and 2014-2015 and identified all cases of definite and probable SUDEP. The estimated rate of SUDEP decreased by about 36% from the first period to the second period. SUDEP rates as a proportion of the total population in those regions also declined.

The investigators also examined differences in estimated SUDEP rates in the United States according to median household income. In New York, the zip codes with the highest SUDEP rates tended to have the lowest median household incomes. The zip codes in the lowest quartile of family household income had a SUDEP rate more than twice as high as that in the zip codes in the highest income quartile. This association held true for the period from 2009-2010 and for 2014-2015.

Dr. Friedman and colleagues received funding from Finding a Cure for Epilepsy and Seizures, which is affiliated with the NYU Comprehensive Epilepsy Center and NYU Langone Health.
 

egreb@mdedge.com

SOURCE: Cihan E et al. AES 2018, Abstract 2.419.

NEW ORLEANS – The population-level rate of sudden unexpected death in epilepsy (SUDEP) may have decreased over time, according to data described at the annual meeting of the American Epilepsy Society. Whether this decrease resulted from an improved understanding of SUDEP risk or a focus on risk-reduction strategies is unknown, said Daniel Friedman, MD, associate professor of neurology at the New York University Langone Health.

In addition, the rates of SUDEP in various populations differ according to their socioeconomic status. Differences in access to care are a potential, but unconfirmed, explanation for this association, said Dr. Friedman. Another possible explanation is that confounders such as mental health disorders, substance abuse, and insufficient social support affect individuals’ ability to manage their disorder.

Dr. Friedman and colleagues initially examined SUDEP rates over time in a cohort of patients who received vagus nerve stimulator (VNS) implantation for drug-resistant epilepsy. They analyzed data for 40,443 patients who underwent surgery during 1988-2012. The age-adjusted SUDEP rate per 1,000 person-years of follow-up decreased significantly from 2.47 in years 1-2 to 1.68 in years 3-10. “There was no control group, so we couldn’t necessarily attribute the SUDEP rate reduction to the intervention,” said Dr. Friedman. A study by Tomson et al of patients with epilepsy who received VNS implantation had similar findings.

The literature about the mechanisms of SUDEP and reduction of SUDEP risk has increased in recent years. Neurologists have advocated for greater disclosure to patients of SUDEP risk, as well as better risk counseling. Dr. Friedman and his colleagues decided to investigate whether these factors have affected the risk of SUDEP during the past decade.

They retrospectively examined data for people whose deaths had been investigated at medical examiner’s offices in New York City, San Diego County, and Maryland. They focused on decedents for whom epilepsy or seizure was listed as a cause or contributor to death or as a comorbid condition on the death certificate. They reviewed all available reports, including investigator notes, autopsy reports, and medical records. Next, Dr. Friedman and his colleagues calculated the annual SUDEP rate as a proportion of the general population, estimated using annual Census and American Community Survey data. They used the Mann-Kendall test to analyze the trends in SUDEP rate during 2009-2015.

Of 1,466 deaths in people with epilepsy during this period, 1,124 were classified as definite SUDEP, probable SUDEP, or near SUDEP. Approximately 63% of SUDEP cases were male, and 45% were African-American. The mean age at death was 38 years.

Dr. Friedman’s group found a significant decrease in the overall incidence of SUDEP in the total population during 2009-2015. When they examined the three regions separately, they found decreases in SUDEP incidence in New York City and Maryland, but not in San Diego County. They found no difference in SUDEP rates by season or by day of the week.

In a subsequent analysis, Dr. Friedman and his colleagues adjudicated all deaths related to seizure and epilepsy in the three regions during 2009-2010 and 2014-2015 and identified all cases of definite and probable SUDEP. The estimated rate of SUDEP decreased by about 36% from the first period to the second period. SUDEP rates as a proportion of the total population in those regions also declined.

The investigators also examined differences in estimated SUDEP rates in the United States according to median household income. In New York, the zip codes with the highest SUDEP rates tended to have the lowest median household incomes. The zip codes in the lowest quartile of family household income had a SUDEP rate more than twice as high as that in the zip codes in the highest income quartile. This association held true for the period from 2009-2010 and for 2014-2015.

Dr. Friedman and colleagues received funding from Finding a Cure for Epilepsy and Seizures, which is affiliated with the NYU Comprehensive Epilepsy Center and NYU Langone Health.
 

egreb@mdedge.com

SOURCE: Cihan E et al. AES 2018, Abstract 2.419.

NEW ORLEANS – The population-level rate of sudden unexpected death in epilepsy (SUDEP) may have decreased over time, according to data described at the annual meeting of the American Epilepsy Society. Whether this decrease resulted from an improved understanding of SUDEP risk or a focus on risk-reduction strategies is unknown, said Daniel Friedman, MD, associate professor of neurology at the New York University Langone Health.

In addition, the rates of SUDEP in various populations differ according to their socioeconomic status. Differences in access to care are a potential, but unconfirmed, explanation for this association, said Dr. Friedman. Another possible explanation is that confounders such as mental health disorders, substance abuse, and insufficient social support affect individuals’ ability to manage their disorder.

Dr. Friedman and colleagues initially examined SUDEP rates over time in a cohort of patients who received vagus nerve stimulator (VNS) implantation for drug-resistant epilepsy. They analyzed data for 40,443 patients who underwent surgery during 1988-2012. The age-adjusted SUDEP rate per 1,000 person-years of follow-up decreased significantly from 2.47 in years 1-2 to 1.68 in years 3-10. “There was no control group, so we couldn’t necessarily attribute the SUDEP rate reduction to the intervention,” said Dr. Friedman. A study by Tomson et al of patients with epilepsy who received VNS implantation had similar findings.

The literature about the mechanisms of SUDEP and reduction of SUDEP risk has increased in recent years. Neurologists have advocated for greater disclosure to patients of SUDEP risk, as well as better risk counseling. Dr. Friedman and his colleagues decided to investigate whether these factors have affected the risk of SUDEP during the past decade.

They retrospectively examined data for people whose deaths had been investigated at medical examiner’s offices in New York City, San Diego County, and Maryland. They focused on decedents for whom epilepsy or seizure was listed as a cause or contributor to death or as a comorbid condition on the death certificate. They reviewed all available reports, including investigator notes, autopsy reports, and medical records. Next, Dr. Friedman and his colleagues calculated the annual SUDEP rate as a proportion of the general population, estimated using annual Census and American Community Survey data. They used the Mann-Kendall test to analyze the trends in SUDEP rate during 2009-2015.

Of 1,466 deaths in people with epilepsy during this period, 1,124 were classified as definite SUDEP, probable SUDEP, or near SUDEP. Approximately 63% of SUDEP cases were male, and 45% were African-American. The mean age at death was 38 years.

Dr. Friedman’s group found a significant decrease in the overall incidence of SUDEP in the total population during 2009-2015. When they examined the three regions separately, they found decreases in SUDEP incidence in New York City and Maryland, but not in San Diego County. They found no difference in SUDEP rates by season or by day of the week.

In a subsequent analysis, Dr. Friedman and his colleagues adjudicated all deaths related to seizure and epilepsy in the three regions during 2009-2010 and 2014-2015 and identified all cases of definite and probable SUDEP. The estimated rate of SUDEP decreased by about 36% from the first period to the second period. SUDEP rates as a proportion of the total population in those regions also declined.

The investigators also examined differences in estimated SUDEP rates in the United States according to median household income. In New York, the zip codes with the highest SUDEP rates tended to have the lowest median household incomes. The zip codes in the lowest quartile of family household income had a SUDEP rate more than twice as high as that in the zip codes in the highest income quartile. This association held true for the period from 2009-2010 and for 2014-2015.

Dr. Friedman and colleagues received funding from Finding a Cure for Epilepsy and Seizures, which is affiliated with the NYU Comprehensive Epilepsy Center and NYU Langone Health.
 

egreb@mdedge.com

SOURCE: Cihan E et al. AES 2018, Abstract 2.419.

Adding the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib to platinum doublet chemotherapy modestly improved progression-free survival in a randomized, placebo-controlled, phase 2 trial of 128 patients with extensive-stage non–small cell lung cancer.

Improved progression-free survival (PFS) “did not translate into reduction in overall mortality for patients treated with veliparib. However, the improvement in the point estimate of PFS was quite modest at 6.1 months, compared with 5.5 months [in the placebo control arm],” wrote Taofeek K. Owonikoko, MD, PhD, of Emory University, Atlanta, together with his coinvestigators in the Journal of Clinical Oncology.

Preclinical studies suggest that veliparib helps potentiate standard chemotherapy of non–small cell lung cancer (NSCLC), but clinical trials have yielded mixed results for PARP inhibition in this cancer. Patients in this study had untreated, extensive-stage NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. They received four 3-week cycles of cisplatin-etoposide (75 mg/m² intravenously on day 1 and 100 mg/m² on days 1-3) plus either veliparib (100 mg orally twice per day on days 1-7) or placebo.

Grade 3 or higher lymphopenia and neutropenia were more common in the veliparib arm but did not reduce treatment delivery. After a median follow-up time of 18.5 months, overall response rate was 72% in the veliparib arm versus 66% in the control arm (P =.57). Median overall survival times were 10.3 months and 8.9 months, respectively (hazard ratio, 0.83; P = .17).

The unstratified HR for PFS favored the veliparib-doublet arm but did not reach statistical significance (0.75; P = .06). After stratifying patients by sex and serum lactate dehydrogenase levels, the HR for PFS favored veliparib-doublet chemotherapy (0.63; P = .01). However, veliparib showed a much stronger effect in the subgroup of men with abnormal lactate dehydrogenase levels (adjusted HR, 0.34; P less than .001), which violated the “proportional hazards within strata assumption” on which this model was based, rendering the overall stratified HR uninterpretable, the researchers wrote.

They added that, before pursuing a larger definitive clinical trial, they await results from the ongoing phase 2 M14-361 study, in which patients with extensive-stage NSCLC are receiving platinum doublet therapy with carboplatin-etoposide plus either veliparib or placebo.

Funders included the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group and the National Cancer Institute. Dr. Owonikoko reported ties to Novartis, Astellas Pharma, Celgene, and several other pharmaceutical companies.

SOURCE: Owonikoko TK et al. J Clin Oncol. 2018 Dec 5. doi: 10.1200/JCO.18.00264.

Adding the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib to platinum doublet chemotherapy modestly improved progression-free survival in a randomized, placebo-controlled, phase 2 trial of 128 patients with extensive-stage non–small cell lung cancer.

Improved progression-free survival (PFS) “did not translate into reduction in overall mortality for patients treated with veliparib. However, the improvement in the point estimate of PFS was quite modest at 6.1 months, compared with 5.5 months [in the placebo control arm],” wrote Taofeek K. Owonikoko, MD, PhD, of Emory University, Atlanta, together with his coinvestigators in the Journal of Clinical Oncology.

Preclinical studies suggest that veliparib helps potentiate standard chemotherapy of non–small cell lung cancer (NSCLC), but clinical trials have yielded mixed results for PARP inhibition in this cancer. Patients in this study had untreated, extensive-stage NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. They received four 3-week cycles of cisplatin-etoposide (75 mg/m² intravenously on day 1 and 100 mg/m² on days 1-3) plus either veliparib (100 mg orally twice per day on days 1-7) or placebo.

Grade 3 or higher lymphopenia and neutropenia were more common in the veliparib arm but did not reduce treatment delivery. After a median follow-up time of 18.5 months, overall response rate was 72% in the veliparib arm versus 66% in the control arm (P =.57). Median overall survival times were 10.3 months and 8.9 months, respectively (hazard ratio, 0.83; P = .17).

The unstratified HR for PFS favored the veliparib-doublet arm but did not reach statistical significance (0.75; P = .06). After stratifying patients by sex and serum lactate dehydrogenase levels, the HR for PFS favored veliparib-doublet chemotherapy (0.63; P = .01). However, veliparib showed a much stronger effect in the subgroup of men with abnormal lactate dehydrogenase levels (adjusted HR, 0.34; P less than .001), which violated the “proportional hazards within strata assumption” on which this model was based, rendering the overall stratified HR uninterpretable, the researchers wrote.

They added that, before pursuing a larger definitive clinical trial, they await results from the ongoing phase 2 M14-361 study, in which patients with extensive-stage NSCLC are receiving platinum doublet therapy with carboplatin-etoposide plus either veliparib or placebo.

Funders included the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group and the National Cancer Institute. Dr. Owonikoko reported ties to Novartis, Astellas Pharma, Celgene, and several other pharmaceutical companies.

SOURCE: Owonikoko TK et al. J Clin Oncol. 2018 Dec 5. doi: 10.1200/JCO.18.00264.

Adding the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib to platinum doublet chemotherapy modestly improved progression-free survival in a randomized, placebo-controlled, phase 2 trial of 128 patients with extensive-stage non–small cell lung cancer.

Improved progression-free survival (PFS) “did not translate into reduction in overall mortality for patients treated with veliparib. However, the improvement in the point estimate of PFS was quite modest at 6.1 months, compared with 5.5 months [in the placebo control arm],” wrote Taofeek K. Owonikoko, MD, PhD, of Emory University, Atlanta, together with his coinvestigators in the Journal of Clinical Oncology.

Preclinical studies suggest that veliparib helps potentiate standard chemotherapy of non–small cell lung cancer (NSCLC), but clinical trials have yielded mixed results for PARP inhibition in this cancer. Patients in this study had untreated, extensive-stage NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. They received four 3-week cycles of cisplatin-etoposide (75 mg/m² intravenously on day 1 and 100 mg/m² on days 1-3) plus either veliparib (100 mg orally twice per day on days 1-7) or placebo.

Grade 3 or higher lymphopenia and neutropenia were more common in the veliparib arm but did not reduce treatment delivery. After a median follow-up time of 18.5 months, overall response rate was 72% in the veliparib arm versus 66% in the control arm (P =.57). Median overall survival times were 10.3 months and 8.9 months, respectively (hazard ratio, 0.83; P = .17).

The unstratified HR for PFS favored the veliparib-doublet arm but did not reach statistical significance (0.75; P = .06). After stratifying patients by sex and serum lactate dehydrogenase levels, the HR for PFS favored veliparib-doublet chemotherapy (0.63; P = .01). However, veliparib showed a much stronger effect in the subgroup of men with abnormal lactate dehydrogenase levels (adjusted HR, 0.34; P less than .001), which violated the “proportional hazards within strata assumption” on which this model was based, rendering the overall stratified HR uninterpretable, the researchers wrote.

They added that, before pursuing a larger definitive clinical trial, they await results from the ongoing phase 2 M14-361 study, in which patients with extensive-stage NSCLC are receiving platinum doublet therapy with carboplatin-etoposide plus either veliparib or placebo.

Funders included the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group and the National Cancer Institute. Dr. Owonikoko reported ties to Novartis, Astellas Pharma, Celgene, and several other pharmaceutical companies.

SOURCE: Owonikoko TK et al. J Clin Oncol. 2018 Dec 5. doi: 10.1200/JCO.18.00264.

The 2018-2019 flu season may have peaked as measures of influenza-like illness (ILI) activity dropped in the first week of the new year, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatients visits for ILI dropped to 3.5% for the week ending Jan. 5, 2019, after reaching 4.0% the previous week. Outpatient ILI visits first topped the national baseline of 2.2% during the week ending Dec. 8, 2018, and have remained above that value for 5 consecutive weeks, the CDC’s influenza division said on Jan. 11.

Flu activity reported by the states reflects the national drop: 10 states came in at level 10 on the CDC’s 1-10 scale of activity for the week ending Jan. 5 – down from 12 the week before – and a total of 15 were in the high range from 8 to 10, compared with 19 the previous week, the CDC said. Two states, Mississippi and Texas, dropped from level 10 to level 7, which the CDC categorizes as moderate activity.

A total of 73 ILI-related deaths were reported during the week ending Dec. 29 (the latest with data available; reporting less than 68% complete), which already exceeds the 71 deaths reported for the week ending Dec. 22 (reporting 85% complete). Flu deaths totaled 437 through the first 13 weeks of the 2018-2019 season, compared with the 1,659 that occurred during weeks 1-13 of the very severe 2017-2018 season, CDC data show.

For the week ending Jan. 5, the CDC received reports of three flu-related pediatric deaths, all of which occurred the previous week. For the season so far, there have been 16 pediatric deaths, compared with 20 at this point in the 2017-2018 season.

Estimates released during the flu season for the first time show that between 6 and 7 million Americans have been infected since Oct. 1, 2018, and that 69,000-84,000 people have been hospitalized with the flu through Jan. 5, 2019. These cumulative totals have previously been available only at the end of the season, the CDC noted.

rfranki@mdedge.com

The 2018-2019 flu season may have peaked as measures of influenza-like illness (ILI) activity dropped in the first week of the new year, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatients visits for ILI dropped to 3.5% for the week ending Jan. 5, 2019, after reaching 4.0% the previous week. Outpatient ILI visits first topped the national baseline of 2.2% during the week ending Dec. 8, 2018, and have remained above that value for 5 consecutive weeks, the CDC’s influenza division said on Jan. 11.

Flu activity reported by the states reflects the national drop: 10 states came in at level 10 on the CDC’s 1-10 scale of activity for the week ending Jan. 5 – down from 12 the week before – and a total of 15 were in the high range from 8 to 10, compared with 19 the previous week, the CDC said. Two states, Mississippi and Texas, dropped from level 10 to level 7, which the CDC categorizes as moderate activity.

A total of 73 ILI-related deaths were reported during the week ending Dec. 29 (the latest with data available; reporting less than 68% complete), which already exceeds the 71 deaths reported for the week ending Dec. 22 (reporting 85% complete). Flu deaths totaled 437 through the first 13 weeks of the 2018-2019 season, compared with the 1,659 that occurred during weeks 1-13 of the very severe 2017-2018 season, CDC data show.

For the week ending Jan. 5, the CDC received reports of three flu-related pediatric deaths, all of which occurred the previous week. For the season so far, there have been 16 pediatric deaths, compared with 20 at this point in the 2017-2018 season.

Estimates released during the flu season for the first time show that between 6 and 7 million Americans have been infected since Oct. 1, 2018, and that 69,000-84,000 people have been hospitalized with the flu through Jan. 5, 2019. These cumulative totals have previously been available only at the end of the season, the CDC noted.

rfranki@mdedge.com

The 2018-2019 flu season may have peaked as measures of influenza-like illness (ILI) activity dropped in the first week of the new year, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatients visits for ILI dropped to 3.5% for the week ending Jan. 5, 2019, after reaching 4.0% the previous week. Outpatient ILI visits first topped the national baseline of 2.2% during the week ending Dec. 8, 2018, and have remained above that value for 5 consecutive weeks, the CDC’s influenza division said on Jan. 11.

Flu activity reported by the states reflects the national drop: 10 states came in at level 10 on the CDC’s 1-10 scale of activity for the week ending Jan. 5 – down from 12 the week before – and a total of 15 were in the high range from 8 to 10, compared with 19 the previous week, the CDC said. Two states, Mississippi and Texas, dropped from level 10 to level 7, which the CDC categorizes as moderate activity.

A total of 73 ILI-related deaths were reported during the week ending Dec. 29 (the latest with data available; reporting less than 68% complete), which already exceeds the 71 deaths reported for the week ending Dec. 22 (reporting 85% complete). Flu deaths totaled 437 through the first 13 weeks of the 2018-2019 season, compared with the 1,659 that occurred during weeks 1-13 of the very severe 2017-2018 season, CDC data show.

For the week ending Jan. 5, the CDC received reports of three flu-related pediatric deaths, all of which occurred the previous week. For the season so far, there have been 16 pediatric deaths, compared with 20 at this point in the 2017-2018 season.

Estimates released during the flu season for the first time show that between 6 and 7 million Americans have been infected since Oct. 1, 2018, and that 69,000-84,000 people have been hospitalized with the flu through Jan. 5, 2019. These cumulative totals have previously been available only at the end of the season, the CDC noted.

rfranki@mdedge.com

I suspect, like me, you have never put much stock in astrology. It just doesn’t feel like a good fit with our science-based training. But recent evidence suggests that maybe we should be paying more attention to the whether our patient is a Taurus or a Leo when we are hunting for a diagnosis.

patchareeporn_s/Getty Images

Three researchers from Harvard’s Schools of Medicine and Public Health have followed several hundred thousand children born between 2007 and 2009 until 2016 (“Attention deficit–hyperactivity disorder and month of school enrollment,” N Engl J Med. 2018;379:2122-30). Their data revealed that, in states with a Sept. 1 school entry cutoff, children born in August had rates of diagnosis and treatment of ADHD that were 34% higher than those born in other months.

Their findings could mean that astrology deserves a lot more credibility than we have been giving it. More likely it suggests that those of us committed to the health and education of children deserve a booby prize for objectivity. In a New York Times Op-Ed piece, the study’s investigators point out that their data show that the relative immaturity of the youngest children in a class too often is interpreted as a symptom of ADHD (“The Link Between August Birthdays and ADHD,” 2018 Nov 28. Jena AB et al.).

For many of us who practiced pediatrics before the ADHD phenomenon erupted, this new study substantiates our suspicion that the condition is currently being both overdiagnosed and overtreated. The data leave unanswered the question of whom or what is to blame for starting the epidemic. However, the study does suggest that physicians and educators deserve some culpability by failing to maintain their objectivity when interpreting childhood behavior.

I clearly can recall the first time I spoke to a group of teachers about the articles I had been reading that suggested a beneficial effect of treating “hyperactive” children with stimulant medication. The teachers uniformly were incredulous and repulsed by the counterintuitive notion of medicating children whom they saw as difficult, but not out of the broad range of age and developmental maturity they could expect to see in their classrooms.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

I suspect, like me, you have never put much stock in astrology. It just doesn’t feel like a good fit with our science-based training. But recent evidence suggests that maybe we should be paying more attention to the whether our patient is a Taurus or a Leo when we are hunting for a diagnosis.

patchareeporn_s/Getty Images

Three researchers from Harvard’s Schools of Medicine and Public Health have followed several hundred thousand children born between 2007 and 2009 until 2016 (“Attention deficit–hyperactivity disorder and month of school enrollment,” N Engl J Med. 2018;379:2122-30). Their data revealed that, in states with a Sept. 1 school entry cutoff, children born in August had rates of diagnosis and treatment of ADHD that were 34% higher than those born in other months.

Their findings could mean that astrology deserves a lot more credibility than we have been giving it. More likely it suggests that those of us committed to the health and education of children deserve a booby prize for objectivity. In a New York Times Op-Ed piece, the study’s investigators point out that their data show that the relative immaturity of the youngest children in a class too often is interpreted as a symptom of ADHD (“The Link Between August Birthdays and ADHD,” 2018 Nov 28. Jena AB et al.).

For many of us who practiced pediatrics before the ADHD phenomenon erupted, this new study substantiates our suspicion that the condition is currently being both overdiagnosed and overtreated. The data leave unanswered the question of whom or what is to blame for starting the epidemic. However, the study does suggest that physicians and educators deserve some culpability by failing to maintain their objectivity when interpreting childhood behavior.

I clearly can recall the first time I spoke to a group of teachers about the articles I had been reading that suggested a beneficial effect of treating “hyperactive” children with stimulant medication. The teachers uniformly were incredulous and repulsed by the counterintuitive notion of medicating children whom they saw as difficult, but not out of the broad range of age and developmental maturity they could expect to see in their classrooms.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

I suspect, like me, you have never put much stock in astrology. It just doesn’t feel like a good fit with our science-based training. But recent evidence suggests that maybe we should be paying more attention to the whether our patient is a Taurus or a Leo when we are hunting for a diagnosis.

patchareeporn_s/Getty Images

Three researchers from Harvard’s Schools of Medicine and Public Health have followed several hundred thousand children born between 2007 and 2009 until 2016 (“Attention deficit–hyperactivity disorder and month of school enrollment,” N Engl J Med. 2018;379:2122-30). Their data revealed that, in states with a Sept. 1 school entry cutoff, children born in August had rates of diagnosis and treatment of ADHD that were 34% higher than those born in other months.

Their findings could mean that astrology deserves a lot more credibility than we have been giving it. More likely it suggests that those of us committed to the health and education of children deserve a booby prize for objectivity. In a New York Times Op-Ed piece, the study’s investigators point out that their data show that the relative immaturity of the youngest children in a class too often is interpreted as a symptom of ADHD (“The Link Between August Birthdays and ADHD,” 2018 Nov 28. Jena AB et al.).

For many of us who practiced pediatrics before the ADHD phenomenon erupted, this new study substantiates our suspicion that the condition is currently being both overdiagnosed and overtreated. The data leave unanswered the question of whom or what is to blame for starting the epidemic. However, the study does suggest that physicians and educators deserve some culpability by failing to maintain their objectivity when interpreting childhood behavior.

I clearly can recall the first time I spoke to a group of teachers about the articles I had been reading that suggested a beneficial effect of treating “hyperactive” children with stimulant medication. The teachers uniformly were incredulous and repulsed by the counterintuitive notion of medicating children whom they saw as difficult, but not out of the broad range of age and developmental maturity they could expect to see in their classrooms.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.