Doug Brunk

SAN DIEGO – Greater intake of soy isoflavones has been associated with lower prevalence of asthma in recent studies, but results from the placebo-controlled, federally funded SOYA (Study of Soy Isoflavones in Asthma) trial to assess soy supplements’ impact on asthma control showed that lung function didn’t improve with increased soy isoflavone intake. In a video interview at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, Dr. Lewis Smith of Northwestern University, Chicago, discusses the study's negative results, and what may have been behind the findings.

dbrunk@frontlinemedcom.com

SAN DIEGO – Greater intake of soy isoflavones has been associated with lower prevalence of asthma in recent studies, but results from the placebo-controlled, federally funded SOYA (Study of Soy Isoflavones in Asthma) trial to assess soy supplements’ impact on asthma control showed that lung function didn’t improve with increased soy isoflavone intake. In a video interview at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, Dr. Lewis Smith of Northwestern University, Chicago, discusses the study's negative results, and what may have been behind the findings.

dbrunk@frontlinemedcom.com

SAN DIEGO – Greater intake of soy isoflavones has been associated with lower prevalence of asthma in recent studies, but results from the placebo-controlled, federally funded SOYA (Study of Soy Isoflavones in Asthma) trial to assess soy supplements’ impact on asthma control showed that lung function didn’t improve with increased soy isoflavone intake. In a video interview at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, Dr. Lewis Smith of Northwestern University, Chicago, discusses the study's negative results, and what may have been behind the findings.

dbrunk@frontlinemedcom.com

SAN DIEGO – How safe are asthma medications during pregnancy? And how adherent are pregnant women to asthma medications? Dr. Jennifer A. Namazy of Scripps Clinic, La Jolla, Calif., summarizes the reassuring data on use of asthma medications by pregnant women, and she outlines her own approach to ensure pregnant women with asthma remain healthy and medication adherent.

dbrunk@frontlinemedcom.com

SAN DIEGO – How safe are asthma medications during pregnancy? And how adherent are pregnant women to asthma medications? Dr. Jennifer A. Namazy of Scripps Clinic, La Jolla, Calif., summarizes the reassuring data on use of asthma medications by pregnant women, and she outlines her own approach to ensure pregnant women with asthma remain healthy and medication adherent.

dbrunk@frontlinemedcom.com

SAN DIEGO – How safe are asthma medications during pregnancy? And how adherent are pregnant women to asthma medications? Dr. Jennifer A. Namazy of Scripps Clinic, La Jolla, Calif., summarizes the reassuring data on use of asthma medications by pregnant women, and she outlines her own approach to ensure pregnant women with asthma remain healthy and medication adherent.

dbrunk@frontlinemedcom.com

Benzophenones, chemical ultraviolet light absorbers used in products ranging from sunscreens and hair sprays to plastic lens filters for color photography, have been named the American Contact Dermatitis Society’s 2014 Contact Allergen of the Year.

First used as a preserver to extend the shelf life of paints, varnishes, and other industrial products, benzophenones were added to sunscreens in the 1950s. Other personal care products that may contain benzophenones are hair dyes, perfumes, shampoos, detergent bars, and nail polishes. The agents are still used in number of industrial applications, including plastic lens filters for color photography, aerosol sprays to protect color prints, and transparent shades to protect window displays. According to a feature article in the January/February 2014 issue of the journal Dermatitis, benzophenones-3, -4, -8, and -10 rank as the four agents most commonly used in personal care products. In addition, the amount of benzophenone-3 used in United States sunscreens is more than all other benzophenones combined (Dermatitis 2014;25:3-10).

Today, benzophenone-3 "is not only the most common benzophenone to cause positive patch test reactions, but it also is the most common UV filter, overall, to cause allergy," wrote lead author Ashley R. Heurung, a fourth-year student at the University of Minnesota, Minneapolis, and her associates. "The most recent 10-year retrospective analysis of the North American Contact Dermatitis Group Data (NACDG; 2001-2010) found that of the 219 of 23,908 patch-tested patients with sunscreen listed as an allergen source, 70.2% had positive patch test reactions to benzophenone-3" (Dermatitis 2013;24:176-82).

In an interview, coauthor Erin M. Warshaw, chief of dermatology at the Minneapolis Veterans Affairs Medical Center, said that benzophenones were chosen as Allergen of the Year "to raise awareness that they are becoming more of a common allergen, and [to recommend] that they should be on a standard screening series, because they’re in so many products like sunscreen, shampoo, conditioner, perfumes, and hand sanitizers. If you’re not thinking about sunscreen [as a potential allergen], you’ll miss it," Dr. Warshaw said.

The American Contact Dermatitis Society’s Core Screening Series includes benzophenones, "but most dermatologists use T.R.U.E. Test, a prepackaged kit of 36 allergens," Dr. Warshaw noted. "Benzophenones are not on that series."

Reports of contact dermatitis triggered by benzophenone-4 have appeared in recent medical literature, but data regarding adverse reactions of benzophenones-8 and -10 are scarce. The authors noted that benzophenone-3 is the culprit in more photoallergic contact dermatitis reactions than any other UV filter available, although large photopatch studies have shown that benzophenone-4 is a leading cause of photoallergy in patients with adverse reactions to sunscreens. Benzophenones-10 and -2 also have been implicated in photopatch reaction tests, but no reports of photoallergy to benzophenone-8 have been documented.

The authors added that benzophenone-3 shows high rates of cross-reactivity with octocrylene and ketoprofen, and that at least two cases of anaphylaxis from topical application of benzophenone-3 have been published (J. Allergy Clin. Immunol. 2001;107:556-7 and Contact Dermatitis 2002;46:55-6). "Both cases resulted in generalized wheal and flare reactions and syncope after widespread application of a sunscreen or sunless tanning product with this filter," they wrote. "Contact urticaria developed after more limited exposure to benzophenone-3 in both cases."

The authors stated that they had relevant conflicts to disclose.

dbrunk@frontlinemedcom.com

Benzophenones, chemical ultraviolet light absorbers used in products ranging from sunscreens and hair sprays to plastic lens filters for color photography, have been named the American Contact Dermatitis Society’s 2014 Contact Allergen of the Year.

First used as a preserver to extend the shelf life of paints, varnishes, and other industrial products, benzophenones were added to sunscreens in the 1950s. Other personal care products that may contain benzophenones are hair dyes, perfumes, shampoos, detergent bars, and nail polishes. The agents are still used in number of industrial applications, including plastic lens filters for color photography, aerosol sprays to protect color prints, and transparent shades to protect window displays. According to a feature article in the January/February 2014 issue of the journal Dermatitis, benzophenones-3, -4, -8, and -10 rank as the four agents most commonly used in personal care products. In addition, the amount of benzophenone-3 used in United States sunscreens is more than all other benzophenones combined (Dermatitis 2014;25:3-10).

Today, benzophenone-3 "is not only the most common benzophenone to cause positive patch test reactions, but it also is the most common UV filter, overall, to cause allergy," wrote lead author Ashley R. Heurung, a fourth-year student at the University of Minnesota, Minneapolis, and her associates. "The most recent 10-year retrospective analysis of the North American Contact Dermatitis Group Data (NACDG; 2001-2010) found that of the 219 of 23,908 patch-tested patients with sunscreen listed as an allergen source, 70.2% had positive patch test reactions to benzophenone-3" (Dermatitis 2013;24:176-82).

In an interview, coauthor Erin M. Warshaw, chief of dermatology at the Minneapolis Veterans Affairs Medical Center, said that benzophenones were chosen as Allergen of the Year "to raise awareness that they are becoming more of a common allergen, and [to recommend] that they should be on a standard screening series, because they’re in so many products like sunscreen, shampoo, conditioner, perfumes, and hand sanitizers. If you’re not thinking about sunscreen [as a potential allergen], you’ll miss it," Dr. Warshaw said.

The American Contact Dermatitis Society’s Core Screening Series includes benzophenones, "but most dermatologists use T.R.U.E. Test, a prepackaged kit of 36 allergens," Dr. Warshaw noted. "Benzophenones are not on that series."

Reports of contact dermatitis triggered by benzophenone-4 have appeared in recent medical literature, but data regarding adverse reactions of benzophenones-8 and -10 are scarce. The authors noted that benzophenone-3 is the culprit in more photoallergic contact dermatitis reactions than any other UV filter available, although large photopatch studies have shown that benzophenone-4 is a leading cause of photoallergy in patients with adverse reactions to sunscreens. Benzophenones-10 and -2 also have been implicated in photopatch reaction tests, but no reports of photoallergy to benzophenone-8 have been documented.

The authors added that benzophenone-3 shows high rates of cross-reactivity with octocrylene and ketoprofen, and that at least two cases of anaphylaxis from topical application of benzophenone-3 have been published (J. Allergy Clin. Immunol. 2001;107:556-7 and Contact Dermatitis 2002;46:55-6). "Both cases resulted in generalized wheal and flare reactions and syncope after widespread application of a sunscreen or sunless tanning product with this filter," they wrote. "Contact urticaria developed after more limited exposure to benzophenone-3 in both cases."

The authors stated that they had relevant conflicts to disclose.

dbrunk@frontlinemedcom.com

Benzophenones, chemical ultraviolet light absorbers used in products ranging from sunscreens and hair sprays to plastic lens filters for color photography, have been named the American Contact Dermatitis Society’s 2014 Contact Allergen of the Year.

First used as a preserver to extend the shelf life of paints, varnishes, and other industrial products, benzophenones were added to sunscreens in the 1950s. Other personal care products that may contain benzophenones are hair dyes, perfumes, shampoos, detergent bars, and nail polishes. The agents are still used in number of industrial applications, including plastic lens filters for color photography, aerosol sprays to protect color prints, and transparent shades to protect window displays. According to a feature article in the January/February 2014 issue of the journal Dermatitis, benzophenones-3, -4, -8, and -10 rank as the four agents most commonly used in personal care products. In addition, the amount of benzophenone-3 used in United States sunscreens is more than all other benzophenones combined (Dermatitis 2014;25:3-10).

Today, benzophenone-3 "is not only the most common benzophenone to cause positive patch test reactions, but it also is the most common UV filter, overall, to cause allergy," wrote lead author Ashley R. Heurung, a fourth-year student at the University of Minnesota, Minneapolis, and her associates. "The most recent 10-year retrospective analysis of the North American Contact Dermatitis Group Data (NACDG; 2001-2010) found that of the 219 of 23,908 patch-tested patients with sunscreen listed as an allergen source, 70.2% had positive patch test reactions to benzophenone-3" (Dermatitis 2013;24:176-82).

In an interview, coauthor Erin M. Warshaw, chief of dermatology at the Minneapolis Veterans Affairs Medical Center, said that benzophenones were chosen as Allergen of the Year "to raise awareness that they are becoming more of a common allergen, and [to recommend] that they should be on a standard screening series, because they’re in so many products like sunscreen, shampoo, conditioner, perfumes, and hand sanitizers. If you’re not thinking about sunscreen [as a potential allergen], you’ll miss it," Dr. Warshaw said.

The American Contact Dermatitis Society’s Core Screening Series includes benzophenones, "but most dermatologists use T.R.U.E. Test, a prepackaged kit of 36 allergens," Dr. Warshaw noted. "Benzophenones are not on that series."

Reports of contact dermatitis triggered by benzophenone-4 have appeared in recent medical literature, but data regarding adverse reactions of benzophenones-8 and -10 are scarce. The authors noted that benzophenone-3 is the culprit in more photoallergic contact dermatitis reactions than any other UV filter available, although large photopatch studies have shown that benzophenone-4 is a leading cause of photoallergy in patients with adverse reactions to sunscreens. Benzophenones-10 and -2 also have been implicated in photopatch reaction tests, but no reports of photoallergy to benzophenone-8 have been documented.

The authors added that benzophenone-3 shows high rates of cross-reactivity with octocrylene and ketoprofen, and that at least two cases of anaphylaxis from topical application of benzophenone-3 have been published (J. Allergy Clin. Immunol. 2001;107:556-7 and Contact Dermatitis 2002;46:55-6). "Both cases resulted in generalized wheal and flare reactions and syncope after widespread application of a sunscreen or sunless tanning product with this filter," they wrote. "Contact urticaria developed after more limited exposure to benzophenone-3 in both cases."

The authors stated that they had relevant conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Results from studies conducted to date indicate that anti-PD-L1 therapy is well tolerated in patients with non–small cell lung cancer, with rapid response rates.

Responses are "not only very rapid, they’re also very durable," Dr. Leora Horn said at the Joint Conference on the Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

"We’re seeing continued responses even when treatment is discontinued. The response rates appear to be somewhat higher in tumors that express PD-L1, and we see no pneumonitis or treatment-related grade 5 adverse events to date."

The four anti-PD-L1 agents that have been investigated or are currently being investigated in patients with non–small cell lung cancer (NSCLC) are BMS-936559, MPDL3280A, MEDI-4736, and MSB0010718C, said Dr. Horn, clinical director of the thoracic oncology research program at Vanderbilt University, Nashville, Tenn.

BMS-936559, developed by Bristol-Myers Squibb, was part of a phase IA dose study at 0.3, 1, 3, and 10 mg/kg in patients with multiple tumor types including NSCLC. Of the 207 patients enrolled, 75 had NSCLC (N. Engl. J. Med 2012;366:2455-65).

More than half of all patients (61%) had treatment-related adverse events, with fatigue the most common (16%), followed by infusion reaction (10%) and diarrhea (9%). Grade 3 and 4 adverse events occurred in 9% of patients. "One of the themes with anti-PD-L1 therapy is that we’re not seeing grade 3-5 pneumonitis in these like we have seen with anti-PD-1 agents," said Dr. Horn. "This may have to do with different expression of PD-1 and PD-2 within the body and the targets of PD-1 compared to anti-PD-L1 antibodies."

The response rate among NSCLC patients treated in the trial reached about 10%, and responses were seen in squamous and nonsquamous NSCLC. "This agent is not being further developed in NSCLC patients," Dr. Horn said. "Nivolumab, a PD-1- blocking antibody, has really taken over as far as development for Bristol-Myers Squibb."

The next agent she discussed, MPDL3280A, is being developed by Roche and Genentech. A phase I trial presented at the 2013 European Society for Medical Oncology (ESMO) Congress examined different doses in 85 patients with NSCLC ranging from 10 to 20 mg/kg once every week for just under 1 year. Key eligibility criteria were measurable disease per Response Evaluation Criteria in Solid Tumors v1.1 and Eastern Cooperative Oncology Group Performance Status 0 or 1. Dr. Horn said that the majority of adverse events were grade 1-2 and did not require intervention. "There was also no maximum tolerated dose or dose-limiting toxicities, and no grade 3-5 pneumonitis was observed," she said.

In a study of MPDL3280A presented by Dr. Horn and her associates at the 2013 World Conference on Lung Cancer, the clinical impact was assessed in 53 patients with NSCLC. Patients first dosed at 1-20 mg/kg by Oct. 1, 2012, with data cutoff on April 30, 2013. The response rate was 83% among patients who had an immunohistochemistry (IHC) score of 3, 46% among those who were IHC 2 and 3, and 31% among those who were IHC 1, 2, and 3. "In all-comers the response rate was 23%," Dr. Horn said. "The responses in these patients are very rapid. We see them by their first or second CT [computed tomography] scan. The responses are also very durable regardless of their IHC status and in patients who are PD-L1 negative. They’ve also been responding even after treatment has been discontinued."

She and her associates examined the response rate to MPDL3280A based on smoking status and mutational status. The response rate was higher in patients who were current or former smokers compared with never smokers (26% vs. 10%, respectively). By molecular status, the response rate in EGFR [epidermal growth factor receptor] wild-type patients was 26%, compared with 17% in EGFR mutant patients. In addition, there was a 30% response rate in patients who were KRAS wild-type and a 10% response rate in KRAS mutant patients, although the numbers are very small, she noted.

Dr. Horn said there are three separate, ongoing studies looking at MPDL3280A in NSCLC patients: one in patients with PD-L1-positive NSCLC, one in combination with bevacizumab and/or chemotherapy, and one randomized phase III trial comparing the agent with docetaxel in patients after platinum failure.

Data on the next agent Dr. Horn discussed, MEDI-4736 from MedImmune, are limited. A study was presented at the 2013 ESMO Congress and included 11 patients who received doses of 0.1, 0.3, and 1.0 mg/kg. The most common adverse events were diarrhea, vomiting, and dizziness (18% each), and no grade 3 or 4 adverse events or pneumonitis have been reported to date.

Pharmacokinetic studies of MEDI-4736 indicate a dose-dependent increase in target engagement, consistent with binding of the agent to PD-L1. Initial clinical data on eight patients demonstrated response at all different dose levels, ranging from 42% to 80%. "This involves small subsets of patients, so hopefully we’ll see more data on this agent in the next couple of years," Dr. Horn said.

The final anti-PD-L1 in clinical development is MSB0010718C from EMD Serono, but no data are available yet. A three-dose escalation study up to 10 mg/kg is underway. "Hopefully, we’ll see some data on this later this year," Dr. Horn said.

Dr. Horn disclosed that she is a speaker for Bristol-Myers Squibb, Theradex, and other companies.

SAN DIEGO – Results from studies conducted to date indicate that anti-PD-L1 therapy is well tolerated in patients with non–small cell lung cancer, with rapid response rates.

Responses are "not only very rapid, they’re also very durable," Dr. Leora Horn said at the Joint Conference on the Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

"We’re seeing continued responses even when treatment is discontinued. The response rates appear to be somewhat higher in tumors that express PD-L1, and we see no pneumonitis or treatment-related grade 5 adverse events to date."

The four anti-PD-L1 agents that have been investigated or are currently being investigated in patients with non–small cell lung cancer (NSCLC) are BMS-936559, MPDL3280A, MEDI-4736, and MSB0010718C, said Dr. Horn, clinical director of the thoracic oncology research program at Vanderbilt University, Nashville, Tenn.

BMS-936559, developed by Bristol-Myers Squibb, was part of a phase IA dose study at 0.3, 1, 3, and 10 mg/kg in patients with multiple tumor types including NSCLC. Of the 207 patients enrolled, 75 had NSCLC (N. Engl. J. Med 2012;366:2455-65).

More than half of all patients (61%) had treatment-related adverse events, with fatigue the most common (16%), followed by infusion reaction (10%) and diarrhea (9%). Grade 3 and 4 adverse events occurred in 9% of patients. "One of the themes with anti-PD-L1 therapy is that we’re not seeing grade 3-5 pneumonitis in these like we have seen with anti-PD-1 agents," said Dr. Horn. "This may have to do with different expression of PD-1 and PD-2 within the body and the targets of PD-1 compared to anti-PD-L1 antibodies."

The response rate among NSCLC patients treated in the trial reached about 10%, and responses were seen in squamous and nonsquamous NSCLC. "This agent is not being further developed in NSCLC patients," Dr. Horn said. "Nivolumab, a PD-1- blocking antibody, has really taken over as far as development for Bristol-Myers Squibb."

The next agent she discussed, MPDL3280A, is being developed by Roche and Genentech. A phase I trial presented at the 2013 European Society for Medical Oncology (ESMO) Congress examined different doses in 85 patients with NSCLC ranging from 10 to 20 mg/kg once every week for just under 1 year. Key eligibility criteria were measurable disease per Response Evaluation Criteria in Solid Tumors v1.1 and Eastern Cooperative Oncology Group Performance Status 0 or 1. Dr. Horn said that the majority of adverse events were grade 1-2 and did not require intervention. "There was also no maximum tolerated dose or dose-limiting toxicities, and no grade 3-5 pneumonitis was observed," she said.

In a study of MPDL3280A presented by Dr. Horn and her associates at the 2013 World Conference on Lung Cancer, the clinical impact was assessed in 53 patients with NSCLC. Patients first dosed at 1-20 mg/kg by Oct. 1, 2012, with data cutoff on April 30, 2013. The response rate was 83% among patients who had an immunohistochemistry (IHC) score of 3, 46% among those who were IHC 2 and 3, and 31% among those who were IHC 1, 2, and 3. "In all-comers the response rate was 23%," Dr. Horn said. "The responses in these patients are very rapid. We see them by their first or second CT [computed tomography] scan. The responses are also very durable regardless of their IHC status and in patients who are PD-L1 negative. They’ve also been responding even after treatment has been discontinued."

She and her associates examined the response rate to MPDL3280A based on smoking status and mutational status. The response rate was higher in patients who were current or former smokers compared with never smokers (26% vs. 10%, respectively). By molecular status, the response rate in EGFR [epidermal growth factor receptor] wild-type patients was 26%, compared with 17% in EGFR mutant patients. In addition, there was a 30% response rate in patients who were KRAS wild-type and a 10% response rate in KRAS mutant patients, although the numbers are very small, she noted.

Dr. Horn said there are three separate, ongoing studies looking at MPDL3280A in NSCLC patients: one in patients with PD-L1-positive NSCLC, one in combination with bevacizumab and/or chemotherapy, and one randomized phase III trial comparing the agent with docetaxel in patients after platinum failure.

Data on the next agent Dr. Horn discussed, MEDI-4736 from MedImmune, are limited. A study was presented at the 2013 ESMO Congress and included 11 patients who received doses of 0.1, 0.3, and 1.0 mg/kg. The most common adverse events were diarrhea, vomiting, and dizziness (18% each), and no grade 3 or 4 adverse events or pneumonitis have been reported to date.

Pharmacokinetic studies of MEDI-4736 indicate a dose-dependent increase in target engagement, consistent with binding of the agent to PD-L1. Initial clinical data on eight patients demonstrated response at all different dose levels, ranging from 42% to 80%. "This involves small subsets of patients, so hopefully we’ll see more data on this agent in the next couple of years," Dr. Horn said.

The final anti-PD-L1 in clinical development is MSB0010718C from EMD Serono, but no data are available yet. A three-dose escalation study up to 10 mg/kg is underway. "Hopefully, we’ll see some data on this later this year," Dr. Horn said.

Dr. Horn disclosed that she is a speaker for Bristol-Myers Squibb, Theradex, and other companies.

SAN DIEGO – Results from studies conducted to date indicate that anti-PD-L1 therapy is well tolerated in patients with non–small cell lung cancer, with rapid response rates.

Responses are "not only very rapid, they’re also very durable," Dr. Leora Horn said at the Joint Conference on the Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

"We’re seeing continued responses even when treatment is discontinued. The response rates appear to be somewhat higher in tumors that express PD-L1, and we see no pneumonitis or treatment-related grade 5 adverse events to date."

The four anti-PD-L1 agents that have been investigated or are currently being investigated in patients with non–small cell lung cancer (NSCLC) are BMS-936559, MPDL3280A, MEDI-4736, and MSB0010718C, said Dr. Horn, clinical director of the thoracic oncology research program at Vanderbilt University, Nashville, Tenn.

BMS-936559, developed by Bristol-Myers Squibb, was part of a phase IA dose study at 0.3, 1, 3, and 10 mg/kg in patients with multiple tumor types including NSCLC. Of the 207 patients enrolled, 75 had NSCLC (N. Engl. J. Med 2012;366:2455-65).

More than half of all patients (61%) had treatment-related adverse events, with fatigue the most common (16%), followed by infusion reaction (10%) and diarrhea (9%). Grade 3 and 4 adverse events occurred in 9% of patients. "One of the themes with anti-PD-L1 therapy is that we’re not seeing grade 3-5 pneumonitis in these like we have seen with anti-PD-1 agents," said Dr. Horn. "This may have to do with different expression of PD-1 and PD-2 within the body and the targets of PD-1 compared to anti-PD-L1 antibodies."

The response rate among NSCLC patients treated in the trial reached about 10%, and responses were seen in squamous and nonsquamous NSCLC. "This agent is not being further developed in NSCLC patients," Dr. Horn said. "Nivolumab, a PD-1- blocking antibody, has really taken over as far as development for Bristol-Myers Squibb."

The next agent she discussed, MPDL3280A, is being developed by Roche and Genentech. A phase I trial presented at the 2013 European Society for Medical Oncology (ESMO) Congress examined different doses in 85 patients with NSCLC ranging from 10 to 20 mg/kg once every week for just under 1 year. Key eligibility criteria were measurable disease per Response Evaluation Criteria in Solid Tumors v1.1 and Eastern Cooperative Oncology Group Performance Status 0 or 1. Dr. Horn said that the majority of adverse events were grade 1-2 and did not require intervention. "There was also no maximum tolerated dose or dose-limiting toxicities, and no grade 3-5 pneumonitis was observed," she said.

In a study of MPDL3280A presented by Dr. Horn and her associates at the 2013 World Conference on Lung Cancer, the clinical impact was assessed in 53 patients with NSCLC. Patients first dosed at 1-20 mg/kg by Oct. 1, 2012, with data cutoff on April 30, 2013. The response rate was 83% among patients who had an immunohistochemistry (IHC) score of 3, 46% among those who were IHC 2 and 3, and 31% among those who were IHC 1, 2, and 3. "In all-comers the response rate was 23%," Dr. Horn said. "The responses in these patients are very rapid. We see them by their first or second CT [computed tomography] scan. The responses are also very durable regardless of their IHC status and in patients who are PD-L1 negative. They’ve also been responding even after treatment has been discontinued."

She and her associates examined the response rate to MPDL3280A based on smoking status and mutational status. The response rate was higher in patients who were current or former smokers compared with never smokers (26% vs. 10%, respectively). By molecular status, the response rate in EGFR [epidermal growth factor receptor] wild-type patients was 26%, compared with 17% in EGFR mutant patients. In addition, there was a 30% response rate in patients who were KRAS wild-type and a 10% response rate in KRAS mutant patients, although the numbers are very small, she noted.

Dr. Horn said there are three separate, ongoing studies looking at MPDL3280A in NSCLC patients: one in patients with PD-L1-positive NSCLC, one in combination with bevacizumab and/or chemotherapy, and one randomized phase III trial comparing the agent with docetaxel in patients after platinum failure.

Data on the next agent Dr. Horn discussed, MEDI-4736 from MedImmune, are limited. A study was presented at the 2013 ESMO Congress and included 11 patients who received doses of 0.1, 0.3, and 1.0 mg/kg. The most common adverse events were diarrhea, vomiting, and dizziness (18% each), and no grade 3 or 4 adverse events or pneumonitis have been reported to date.

Pharmacokinetic studies of MEDI-4736 indicate a dose-dependent increase in target engagement, consistent with binding of the agent to PD-L1. Initial clinical data on eight patients demonstrated response at all different dose levels, ranging from 42% to 80%. "This involves small subsets of patients, so hopefully we’ll see more data on this agent in the next couple of years," Dr. Horn said.

The final anti-PD-L1 in clinical development is MSB0010718C from EMD Serono, but no data are available yet. A three-dose escalation study up to 10 mg/kg is underway. "Hopefully, we’ll see some data on this later this year," Dr. Horn said.

Dr. Horn disclosed that she is a speaker for Bristol-Myers Squibb, Theradex, and other companies.

LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.

"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."

If clinicians recommend agents whose effectiveness is not well-established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."

Wavebreak Media/Thinkstockphotos.com

One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."

He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2; 2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."

Certain prescription agents might benefit patients with insomnia, he continued. FDA nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H₁-receptor antagonists.

"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said. "One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."

A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."

From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.

Clinicians likely use benzodiazepine receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the non-benzodiazepines (also known as selective benzodiazepine receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin receptor-agonist, and low-dose doxepin.

Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."

Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.

dbrunk@frontlinemedcom.com

LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.

"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."

If clinicians recommend agents whose effectiveness is not well-established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."

Wavebreak Media/Thinkstockphotos.com

One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."

He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2; 2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."

Certain prescription agents might benefit patients with insomnia, he continued. FDA nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H₁-receptor antagonists.

"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said. "One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."

A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."

From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.

Clinicians likely use benzodiazepine receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the non-benzodiazepines (also known as selective benzodiazepine receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin receptor-agonist, and low-dose doxepin.

Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."

Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.

dbrunk@frontlinemedcom.com

LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.

"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."

If clinicians recommend agents whose effectiveness is not well-established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."

Wavebreak Media/Thinkstockphotos.com

One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."

He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2; 2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."

Certain prescription agents might benefit patients with insomnia, he continued. FDA nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H₁-receptor antagonists.

"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said. "One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."

A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."

From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.

Clinicians likely use benzodiazepine receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the non-benzodiazepines (also known as selective benzodiazepine receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin receptor-agonist, and low-dose doxepin.

Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."

Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.

dbrunk@frontlinemedcom.com

LAS VEGAS – Patients with anorexia nervosa rank among the most difficult to manage because of their resistance to treatment, according to Dr. Katherine A. Halmi.

"Patients with this disorder characteristically do not wish to be treated; they are terrified to give up their illness," Dr. Halmi, professor emerita of psychiatry at Weill Cornell Medical College, New York, said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "They know the diagnostic criteria better than most clinicians do. If you ask them, are you afraid of gaining weight? Many of them will say, ‘No, I don’t know what’s happening. I’m not afraid of gaining weight.’ "

Marked by a restriction of calorie intake leading to low body weight, patients with anorexia nervosa also have a disturbance in experience of body weight or shape or undue influence of body weight or shape on self-evaluation. "Patients will focus on certain body parts, like how wide their thighs are, or they will walk in a peculiar way so their thighs won’t touch," explained Dr. Halmi, who founded the eating disorders program at the New York–Presbyterian Hospital/Westchester division. "When they look in the mirror they will focus on their abdomen and become very concerned that they’re too wide. But if you take a photograph of them and show them the photograph, they will acknowledge that they are thin."

The two subgroups of patients with anorexia nervosa include those who lose weight only by restricting what they eat (no binge eating or purging in the past 3 months) and those who lose weight by binge eating/purging (binge eating, self-induced vomiting, or misuse of laxatives or enemas in the past 3 months). The new aspect of diagnosing this in the DSM-5 includes qualifiers for partial remission or full remission. "Partial remission is defined as weight recovery but continued fear/preoccupation with body weight and shape," she said. "Full remission is defined as no criteria for anorexia nervosa met for a sustained period of time."

The severity of anorexia nervosa is measured by body mass index, ranging from mild (body mass index, 17 kg/m² or greater) to moderate (16-16.99 kg/m²), severe (BM, 15-15.99 kg/m²), or extreme (BMI less than 15 kg/m²). The level of severity may be increased for clinical symptoms, functional disability, and the need for supervision. "This is a serious, chronic illness," Dr. Halmi said. "You have to treat these patients sometimes for 2-3 years before they recover."

The psychological characteristics of the illness include a perfectionist need to control, inflexible thinking, obsessive-compulsive features and social withdrawal, and feelings of ineffectiveness. "These patients are not great adventurers," she noted. "They can be bright and accomplishing a lot in school, but inside, they are very afraid of confronting the world and are very insecure." Other characteristics include limited social spontaneity, restrained emotional expression, dependency, maturity fears, depression, and sexual disinterest.

Physical signs can include hypotension, hypothermia, and bradycardia. Those who binge eat and then vomit often present with tooth erosion, poor gum hygiene, swollen parotid glands "so they look like a chipmunk," and abrasions and scars on the dorsum of hands. Other serious long-term consequences of the illness include osteopenia and osteoporosis. "Once a child loses calcium in bones during their development, that can never be replaced; it puts them at risk for fractures in later life," Dr. Halmi said. "What you can do through nutritional rehabilitation is to prevent further mineral loss from the bones."

Certain serum chemistry tests can help you confirm a diagnosis of anorexia nervosa. Leukopenia with relative lymphocytosis is common. "You also want to measure their serum amylase, because if they’re vomiting, most of the time their serum amylase levels will be elevated," she said. In addition, mild metabolic acidosis is suggestive of laxative abuse. Elevated hepatic enzyme levels and hypercholesterolemia may be present, and elevated blood urea nitrogen levels indicate dehydration.

Dr. Halmi underscored the importance of checking for abuse of stimulants, including amphetamines, caffeine, and nicotine, for weight control. Patients who binge and purge "have a high incidence of drug abuse with alcohol or cocaine," she added. "Ipecac may be used to induce vomiting. That can be especially harmful, because ipecac can cause myocardial damage that is irreversible."

According to Dr. Halmi, the mortality for patients with anorexia nervosa is estimated to be about 7% at 10 years. At 30 years the mortality jumps to 18%-21%. The crude mortality is about 5% per decade. "In the long term, 50% of patients will recover, but about 25% will die of their illness, and about 25% will remain chronically ill for a long period of time," she said.

Few randomized, controlled trials of treatment for the illness exist, principally because it’s difficult to enroll an adequate sample size into such studies. "Also, anorexia nervosa patients are resistant to treatment, so to get them to enter a treatment trial is a real effort," she said. "In addition, medical complications can require withdrawal from treatment protocols."

Dr. Halmi described ideal treatment of patients with the illness as multifocused with compatible team personnel. Medical management is necessary, along with nutritional rehabilitation, psychotherapy, and family therapy, which is essential for adolescents, she said. "I emphasize this because once patients reach age 18, they are legal citizens, and you cannot force them to receive treatment unless they are near death. They have to be very ill before you can convince a judge they need to be committed. The longer they stay in their behavior of losing weight in their malnutrition state, the less likely they are to recover. People who are chronically underweight for longer than 6 years do not recover from this illness. Therefore, it’s important to diagnose this disorder and get them into treatment with an experienced team."

Limited positive evidence exists for cognitive-behavioral therapy for adults and family-based therapy for adolescents. Behavioral family therapy has been shown to be effective in five randomized trials. "Parents with high expressed emotion or criticism will do better with their anorectic adolescents in separated rather than whole family therapy," Dr. Halmi said. "In the short term, 10 sessions over 6 months is effective for intact families and patients low in obsessive-compulsive features."

Although about 20 randomized controlled studies of pharmacologic treatment have been performed to date, no "grade A" evidence exists for using medication in patients with anorexia nervosa. Category B evidence supports the use of 100 mg zinc gluconate or 14 mg elemental zinc per day for 2 months or olanzapine 5-15 mg/day. "The main problem in using olanzapine is compliance," Dr. Halmi said.

Negative evidence exists for prescribing antidepressants for patients with this illness, and insufficient evidence exists for using cyproheptadine up to 24 mg/day, but Dr. Halmi said she has found that some patients benefit from cyproheptadine. "It mainly acts not by increasing appetite, but by slightly reducing body movements," she said.

Dr. Halmi said she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

LAS VEGAS – Patients with anorexia nervosa rank among the most difficult to manage because of their resistance to treatment, according to Dr. Katherine A. Halmi.

"Patients with this disorder characteristically do not wish to be treated; they are terrified to give up their illness," Dr. Halmi, professor emerita of psychiatry at Weill Cornell Medical College, New York, said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "They know the diagnostic criteria better than most clinicians do. If you ask them, are you afraid of gaining weight? Many of them will say, ‘No, I don’t know what’s happening. I’m not afraid of gaining weight.’ "

Marked by a restriction of calorie intake leading to low body weight, patients with anorexia nervosa also have a disturbance in experience of body weight or shape or undue influence of body weight or shape on self-evaluation. "Patients will focus on certain body parts, like how wide their thighs are, or they will walk in a peculiar way so their thighs won’t touch," explained Dr. Halmi, who founded the eating disorders program at the New York–Presbyterian Hospital/Westchester division. "When they look in the mirror they will focus on their abdomen and become very concerned that they’re too wide. But if you take a photograph of them and show them the photograph, they will acknowledge that they are thin."

The two subgroups of patients with anorexia nervosa include those who lose weight only by restricting what they eat (no binge eating or purging in the past 3 months) and those who lose weight by binge eating/purging (binge eating, self-induced vomiting, or misuse of laxatives or enemas in the past 3 months). The new aspect of diagnosing this in the DSM-5 includes qualifiers for partial remission or full remission. "Partial remission is defined as weight recovery but continued fear/preoccupation with body weight and shape," she said. "Full remission is defined as no criteria for anorexia nervosa met for a sustained period of time."

The severity of anorexia nervosa is measured by body mass index, ranging from mild (body mass index, 17 kg/m² or greater) to moderate (16-16.99 kg/m²), severe (BM, 15-15.99 kg/m²), or extreme (BMI less than 15 kg/m²). The level of severity may be increased for clinical symptoms, functional disability, and the need for supervision. "This is a serious, chronic illness," Dr. Halmi said. "You have to treat these patients sometimes for 2-3 years before they recover."

The psychological characteristics of the illness include a perfectionist need to control, inflexible thinking, obsessive-compulsive features and social withdrawal, and feelings of ineffectiveness. "These patients are not great adventurers," she noted. "They can be bright and accomplishing a lot in school, but inside, they are very afraid of confronting the world and are very insecure." Other characteristics include limited social spontaneity, restrained emotional expression, dependency, maturity fears, depression, and sexual disinterest.

Physical signs can include hypotension, hypothermia, and bradycardia. Those who binge eat and then vomit often present with tooth erosion, poor gum hygiene, swollen parotid glands "so they look like a chipmunk," and abrasions and scars on the dorsum of hands. Other serious long-term consequences of the illness include osteopenia and osteoporosis. "Once a child loses calcium in bones during their development, that can never be replaced; it puts them at risk for fractures in later life," Dr. Halmi said. "What you can do through nutritional rehabilitation is to prevent further mineral loss from the bones."

Certain serum chemistry tests can help you confirm a diagnosis of anorexia nervosa. Leukopenia with relative lymphocytosis is common. "You also want to measure their serum amylase, because if they’re vomiting, most of the time their serum amylase levels will be elevated," she said. In addition, mild metabolic acidosis is suggestive of laxative abuse. Elevated hepatic enzyme levels and hypercholesterolemia may be present, and elevated blood urea nitrogen levels indicate dehydration.

Dr. Halmi underscored the importance of checking for abuse of stimulants, including amphetamines, caffeine, and nicotine, for weight control. Patients who binge and purge "have a high incidence of drug abuse with alcohol or cocaine," she added. "Ipecac may be used to induce vomiting. That can be especially harmful, because ipecac can cause myocardial damage that is irreversible."

According to Dr. Halmi, the mortality for patients with anorexia nervosa is estimated to be about 7% at 10 years. At 30 years the mortality jumps to 18%-21%. The crude mortality is about 5% per decade. "In the long term, 50% of patients will recover, but about 25% will die of their illness, and about 25% will remain chronically ill for a long period of time," she said.

Few randomized, controlled trials of treatment for the illness exist, principally because it’s difficult to enroll an adequate sample size into such studies. "Also, anorexia nervosa patients are resistant to treatment, so to get them to enter a treatment trial is a real effort," she said. "In addition, medical complications can require withdrawal from treatment protocols."

Dr. Halmi described ideal treatment of patients with the illness as multifocused with compatible team personnel. Medical management is necessary, along with nutritional rehabilitation, psychotherapy, and family therapy, which is essential for adolescents, she said. "I emphasize this because once patients reach age 18, they are legal citizens, and you cannot force them to receive treatment unless they are near death. They have to be very ill before you can convince a judge they need to be committed. The longer they stay in their behavior of losing weight in their malnutrition state, the less likely they are to recover. People who are chronically underweight for longer than 6 years do not recover from this illness. Therefore, it’s important to diagnose this disorder and get them into treatment with an experienced team."

Limited positive evidence exists for cognitive-behavioral therapy for adults and family-based therapy for adolescents. Behavioral family therapy has been shown to be effective in five randomized trials. "Parents with high expressed emotion or criticism will do better with their anorectic adolescents in separated rather than whole family therapy," Dr. Halmi said. "In the short term, 10 sessions over 6 months is effective for intact families and patients low in obsessive-compulsive features."

Although about 20 randomized controlled studies of pharmacologic treatment have been performed to date, no "grade A" evidence exists for using medication in patients with anorexia nervosa. Category B evidence supports the use of 100 mg zinc gluconate or 14 mg elemental zinc per day for 2 months or olanzapine 5-15 mg/day. "The main problem in using olanzapine is compliance," Dr. Halmi said.

Negative evidence exists for prescribing antidepressants for patients with this illness, and insufficient evidence exists for using cyproheptadine up to 24 mg/day, but Dr. Halmi said she has found that some patients benefit from cyproheptadine. "It mainly acts not by increasing appetite, but by slightly reducing body movements," she said.

Dr. Halmi said she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

LAS VEGAS – Patients with anorexia nervosa rank among the most difficult to manage because of their resistance to treatment, according to Dr. Katherine A. Halmi.

"Patients with this disorder characteristically do not wish to be treated; they are terrified to give up their illness," Dr. Halmi, professor emerita of psychiatry at Weill Cornell Medical College, New York, said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "They know the diagnostic criteria better than most clinicians do. If you ask them, are you afraid of gaining weight? Many of them will say, ‘No, I don’t know what’s happening. I’m not afraid of gaining weight.’ "

Marked by a restriction of calorie intake leading to low body weight, patients with anorexia nervosa also have a disturbance in experience of body weight or shape or undue influence of body weight or shape on self-evaluation. "Patients will focus on certain body parts, like how wide their thighs are, or they will walk in a peculiar way so their thighs won’t touch," explained Dr. Halmi, who founded the eating disorders program at the New York–Presbyterian Hospital/Westchester division. "When they look in the mirror they will focus on their abdomen and become very concerned that they’re too wide. But if you take a photograph of them and show them the photograph, they will acknowledge that they are thin."

The two subgroups of patients with anorexia nervosa include those who lose weight only by restricting what they eat (no binge eating or purging in the past 3 months) and those who lose weight by binge eating/purging (binge eating, self-induced vomiting, or misuse of laxatives or enemas in the past 3 months). The new aspect of diagnosing this in the DSM-5 includes qualifiers for partial remission or full remission. "Partial remission is defined as weight recovery but continued fear/preoccupation with body weight and shape," she said. "Full remission is defined as no criteria for anorexia nervosa met for a sustained period of time."

The severity of anorexia nervosa is measured by body mass index, ranging from mild (body mass index, 17 kg/m² or greater) to moderate (16-16.99 kg/m²), severe (BM, 15-15.99 kg/m²), or extreme (BMI less than 15 kg/m²). The level of severity may be increased for clinical symptoms, functional disability, and the need for supervision. "This is a serious, chronic illness," Dr. Halmi said. "You have to treat these patients sometimes for 2-3 years before they recover."

The psychological characteristics of the illness include a perfectionist need to control, inflexible thinking, obsessive-compulsive features and social withdrawal, and feelings of ineffectiveness. "These patients are not great adventurers," she noted. "They can be bright and accomplishing a lot in school, but inside, they are very afraid of confronting the world and are very insecure." Other characteristics include limited social spontaneity, restrained emotional expression, dependency, maturity fears, depression, and sexual disinterest.

Physical signs can include hypotension, hypothermia, and bradycardia. Those who binge eat and then vomit often present with tooth erosion, poor gum hygiene, swollen parotid glands "so they look like a chipmunk," and abrasions and scars on the dorsum of hands. Other serious long-term consequences of the illness include osteopenia and osteoporosis. "Once a child loses calcium in bones during their development, that can never be replaced; it puts them at risk for fractures in later life," Dr. Halmi said. "What you can do through nutritional rehabilitation is to prevent further mineral loss from the bones."

Certain serum chemistry tests can help you confirm a diagnosis of anorexia nervosa. Leukopenia with relative lymphocytosis is common. "You also want to measure their serum amylase, because if they’re vomiting, most of the time their serum amylase levels will be elevated," she said. In addition, mild metabolic acidosis is suggestive of laxative abuse. Elevated hepatic enzyme levels and hypercholesterolemia may be present, and elevated blood urea nitrogen levels indicate dehydration.

Dr. Halmi underscored the importance of checking for abuse of stimulants, including amphetamines, caffeine, and nicotine, for weight control. Patients who binge and purge "have a high incidence of drug abuse with alcohol or cocaine," she added. "Ipecac may be used to induce vomiting. That can be especially harmful, because ipecac can cause myocardial damage that is irreversible."

According to Dr. Halmi, the mortality for patients with anorexia nervosa is estimated to be about 7% at 10 years. At 30 years the mortality jumps to 18%-21%. The crude mortality is about 5% per decade. "In the long term, 50% of patients will recover, but about 25% will die of their illness, and about 25% will remain chronically ill for a long period of time," she said.

Few randomized, controlled trials of treatment for the illness exist, principally because it’s difficult to enroll an adequate sample size into such studies. "Also, anorexia nervosa patients are resistant to treatment, so to get them to enter a treatment trial is a real effort," she said. "In addition, medical complications can require withdrawal from treatment protocols."

Dr. Halmi described ideal treatment of patients with the illness as multifocused with compatible team personnel. Medical management is necessary, along with nutritional rehabilitation, psychotherapy, and family therapy, which is essential for adolescents, she said. "I emphasize this because once patients reach age 18, they are legal citizens, and you cannot force them to receive treatment unless they are near death. They have to be very ill before you can convince a judge they need to be committed. The longer they stay in their behavior of losing weight in their malnutrition state, the less likely they are to recover. People who are chronically underweight for longer than 6 years do not recover from this illness. Therefore, it’s important to diagnose this disorder and get them into treatment with an experienced team."

Limited positive evidence exists for cognitive-behavioral therapy for adults and family-based therapy for adolescents. Behavioral family therapy has been shown to be effective in five randomized trials. "Parents with high expressed emotion or criticism will do better with their anorectic adolescents in separated rather than whole family therapy," Dr. Halmi said. "In the short term, 10 sessions over 6 months is effective for intact families and patients low in obsessive-compulsive features."

Although about 20 randomized controlled studies of pharmacologic treatment have been performed to date, no "grade A" evidence exists for using medication in patients with anorexia nervosa. Category B evidence supports the use of 100 mg zinc gluconate or 14 mg elemental zinc per day for 2 months or olanzapine 5-15 mg/day. "The main problem in using olanzapine is compliance," Dr. Halmi said.

Negative evidence exists for prescribing antidepressants for patients with this illness, and insufficient evidence exists for using cyproheptadine up to 24 mg/day, but Dr. Halmi said she has found that some patients benefit from cyproheptadine. "It mainly acts not by increasing appetite, but by slightly reducing body movements," she said.

Dr. Halmi said she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Asthma and airway hyperresponsiveness may be underrecognized in children with eosinophilic esophagitis, results from a controlled cross-sectional study demonstrated.

While previous studies have estimated the prevalence of asthma in children with eosinophilic esophagitis (EoE), to range from 24-42%, a recent analysis presented during a late-breaker abstract session at annual meeting of the American Academy of Allergy, Asthma, and Immunology found that up to 70% of children with EoE may suffer from asthma.

pelvidge/thinkstockphotos.com

"Clinicians treating children with eosinophilic esophagitis should consider asking additional history questions related to asthma symptoms and may also want to consider pulmonary function testing or referral to an asthma specialist for evaluation," lead author Dr. Nadia L. Krupp said in an interview prior to the meeting. "This is the first study to formally evaluate lung function and airway hyperresponsiveness in children with EoE. Prior estimations of asthma have solely come from patient/parent report."

Dr. Krupp, director of the Riley Asthma Care Center in the section of pulmonology, allergy, and critical care medicine at Riley Hospital Children, Indianapolis, and her associates conducted a cross-sectional study of 33 children aged 6-18 years with EoE and 37 healthy controls. The researchers performed methacholine challenge (airway hyperresponsiveness defined as provocative concentration of methacholine less than 8mg/mL), and exhaled nitric oxide. They also analyzed peripheral blood for total IgE, eosinophil count, eotaxin, and serum cytokines.

Baseline spirometry did not significantly differ between EoE subjects and healthy controls. However, airway hyperresponsiveness was present in 33% of children with EoE, compared with only 10.8% of healthy controls (P = .04). In addition, 20% of the 15 EoE subjects with asthma had airway hyperresponsiveness, compared with 44% of the 18 EoE subjects without asthma. Overall, 69.7% of EoE subjects had either asthma or airway hyperresponsiveness.

The researchers found that airway hyperresponsiveness correlated strongly with serum IgE (P less than .0001) and exhaled nitric oxide (P = .0002), while epidermal growth factor (EGF) and fibroblastic growth factor–2 (FGF-2) were elevated in subjects with EoE and asthma, compared to healthy controls and those with EoE but no asthma (P less than .05). In addition, subjects with EoE and asthma who were on asthma controller medications had similar levels of EGF and FGF-2 as healthy controls, while Th2 cytokines and eotaxin did not differ significantly among any groups.

Dr. Krupp said she was surprised "by the fact that airway hyperresponsiveness was more prevalent in those subjects without a history of asthma than those with a known diagnosis, and the fact that Th2-related cytokines were not significantly different between healthy controls and EoE subjects."

She acknowledged certain limitations of the study, including its cross-sectional design and "the fact EoE subjects may have had significant variability in the current activity of their esophageal disease at the time of enrollment."

The study was partially funded by Aerocrine. Dr. Krupp said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Asthma and airway hyperresponsiveness may be underrecognized in children with eosinophilic esophagitis, results from a controlled cross-sectional study demonstrated.

While previous studies have estimated the prevalence of asthma in children with eosinophilic esophagitis (EoE), to range from 24-42%, a recent analysis presented during a late-breaker abstract session at annual meeting of the American Academy of Allergy, Asthma, and Immunology found that up to 70% of children with EoE may suffer from asthma.

pelvidge/thinkstockphotos.com

"Clinicians treating children with eosinophilic esophagitis should consider asking additional history questions related to asthma symptoms and may also want to consider pulmonary function testing or referral to an asthma specialist for evaluation," lead author Dr. Nadia L. Krupp said in an interview prior to the meeting. "This is the first study to formally evaluate lung function and airway hyperresponsiveness in children with EoE. Prior estimations of asthma have solely come from patient/parent report."

Dr. Krupp, director of the Riley Asthma Care Center in the section of pulmonology, allergy, and critical care medicine at Riley Hospital Children, Indianapolis, and her associates conducted a cross-sectional study of 33 children aged 6-18 years with EoE and 37 healthy controls. The researchers performed methacholine challenge (airway hyperresponsiveness defined as provocative concentration of methacholine less than 8mg/mL), and exhaled nitric oxide. They also analyzed peripheral blood for total IgE, eosinophil count, eotaxin, and serum cytokines.

Baseline spirometry did not significantly differ between EoE subjects and healthy controls. However, airway hyperresponsiveness was present in 33% of children with EoE, compared with only 10.8% of healthy controls (P = .04). In addition, 20% of the 15 EoE subjects with asthma had airway hyperresponsiveness, compared with 44% of the 18 EoE subjects without asthma. Overall, 69.7% of EoE subjects had either asthma or airway hyperresponsiveness.

The researchers found that airway hyperresponsiveness correlated strongly with serum IgE (P less than .0001) and exhaled nitric oxide (P = .0002), while epidermal growth factor (EGF) and fibroblastic growth factor–2 (FGF-2) were elevated in subjects with EoE and asthma, compared to healthy controls and those with EoE but no asthma (P less than .05). In addition, subjects with EoE and asthma who were on asthma controller medications had similar levels of EGF and FGF-2 as healthy controls, while Th2 cytokines and eotaxin did not differ significantly among any groups.

Dr. Krupp said she was surprised "by the fact that airway hyperresponsiveness was more prevalent in those subjects without a history of asthma than those with a known diagnosis, and the fact that Th2-related cytokines were not significantly different between healthy controls and EoE subjects."

She acknowledged certain limitations of the study, including its cross-sectional design and "the fact EoE subjects may have had significant variability in the current activity of their esophageal disease at the time of enrollment."

The study was partially funded by Aerocrine. Dr. Krupp said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Asthma and airway hyperresponsiveness may be underrecognized in children with eosinophilic esophagitis, results from a controlled cross-sectional study demonstrated.

While previous studies have estimated the prevalence of asthma in children with eosinophilic esophagitis (EoE), to range from 24-42%, a recent analysis presented during a late-breaker abstract session at annual meeting of the American Academy of Allergy, Asthma, and Immunology found that up to 70% of children with EoE may suffer from asthma.

pelvidge/thinkstockphotos.com

"Clinicians treating children with eosinophilic esophagitis should consider asking additional history questions related to asthma symptoms and may also want to consider pulmonary function testing or referral to an asthma specialist for evaluation," lead author Dr. Nadia L. Krupp said in an interview prior to the meeting. "This is the first study to formally evaluate lung function and airway hyperresponsiveness in children with EoE. Prior estimations of asthma have solely come from patient/parent report."

Dr. Krupp, director of the Riley Asthma Care Center in the section of pulmonology, allergy, and critical care medicine at Riley Hospital Children, Indianapolis, and her associates conducted a cross-sectional study of 33 children aged 6-18 years with EoE and 37 healthy controls. The researchers performed methacholine challenge (airway hyperresponsiveness defined as provocative concentration of methacholine less than 8mg/mL), and exhaled nitric oxide. They also analyzed peripheral blood for total IgE, eosinophil count, eotaxin, and serum cytokines.

Baseline spirometry did not significantly differ between EoE subjects and healthy controls. However, airway hyperresponsiveness was present in 33% of children with EoE, compared with only 10.8% of healthy controls (P = .04). In addition, 20% of the 15 EoE subjects with asthma had airway hyperresponsiveness, compared with 44% of the 18 EoE subjects without asthma. Overall, 69.7% of EoE subjects had either asthma or airway hyperresponsiveness.

The researchers found that airway hyperresponsiveness correlated strongly with serum IgE (P less than .0001) and exhaled nitric oxide (P = .0002), while epidermal growth factor (EGF) and fibroblastic growth factor–2 (FGF-2) were elevated in subjects with EoE and asthma, compared to healthy controls and those with EoE but no asthma (P less than .05). In addition, subjects with EoE and asthma who were on asthma controller medications had similar levels of EGF and FGF-2 as healthy controls, while Th2 cytokines and eotaxin did not differ significantly among any groups.

Dr. Krupp said she was surprised "by the fact that airway hyperresponsiveness was more prevalent in those subjects without a history of asthma than those with a known diagnosis, and the fact that Th2-related cytokines were not significantly different between healthy controls and EoE subjects."

She acknowledged certain limitations of the study, including its cross-sectional design and "the fact EoE subjects may have had significant variability in the current activity of their esophageal disease at the time of enrollment."

The study was partially funded by Aerocrine. Dr. Krupp said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Women with chronic rhinosinusitis and co-occurring nasal polyps appear to harbor more severe disease, compared with men, results from a large retrospective study demonstrate.

"For now, these are very preliminary studies, so there is not a lot of clinical application," Kathryn E. Hulse, Ph.D., said in an interview before the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the work was presented. "The hope is that if we can figure out why chronic rhinosinusitis with nasal polyps is more severe in women, we would be able to design better therapeutic strategies to treat this disease in both men and women."

Up to half of patients with chronic rhinosinusitis have comorbid asthma, and Dr. Hulse and her associates at Northwestern University, Chicago, have previously reported that a subset of chronic rhinosinusitis patients with nasal polyps (CRSwNP) have elevated autoantigen-specific antibodies within their nasal polyps (J. Allergy Clin. Immunol. 2011;128:1198-206). In what she said is the first study of its kind, Dr. Hulse of the school’s division of allergy and immunology, and her associates retrospectively reviewed a database of 1,240 patients who underwent nasal surgery or were treated for CRS at Northwestern. They evaluated the effect of gender on the prevalence of CRSwNP, aspirin sensitivity, and asthma status, and used enzyme-linked immunosorbent assay to compare levels of eosinophil cationic protein and anti-dsDNA antibodies in NP extracts from men and women.

Mean patient age was 41 years, and 48% were women. Although women comprised about 50% of controls and CRS patients without NP, a significantly smaller proportion of CRSwNP patients were female (35%). Women with CRSwNP were significantly more likely to have comorbid asthma, and 65% of patients with aspirin-exacerbated respiratory disease (CRSwNP plus asthma and aspirin sensitivity) were women. Asthmatic women with CRSwNP had the highest levels of autoantigen-specific IgG and eosinophil cationic protein, and were significantly more likely to have revision surgeries.

"We thought we would find that CRSwNP was more prevalent and severe in women, especially because these patients have asthma and some features of local autoimmunity, which can be more prevalent and severe in women," Dr. Hulse said. "Instead, we found that men were more likely to have CRSwNP than women, but women did seem to have more severe disease."

She acknowledged certain limitations of the study, including the fact that it focused solely on patients receiving care at a tertiary care center, "so we do not know if these results would be similar if we looked at the general population of people with CRSwNP who do not seek out specialized care. Also, these data were collected for patients at only one location, so we also do not know if the results would be similar at other tertiary care centers."

During a press briefing at the meeting, Dr. Hulse characterized the findings as "an important first step in identifying a potential area of future research and providing the justification for doing larger studies to see if this holds true in a larger population [of patients] or at other sites."

The study was funded by grants from the National Institutes of Health, including the Building Interdisciplinary Research Careers in Women’s Health program. Dr. Hulse said that she had no relevant financial conflicts.

dbrunk@frontlinemedcom.com

SAN DIEGO – Women with chronic rhinosinusitis and co-occurring nasal polyps appear to harbor more severe disease, compared with men, results from a large retrospective study demonstrate.

"For now, these are very preliminary studies, so there is not a lot of clinical application," Kathryn E. Hulse, Ph.D., said in an interview before the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the work was presented. "The hope is that if we can figure out why chronic rhinosinusitis with nasal polyps is more severe in women, we would be able to design better therapeutic strategies to treat this disease in both men and women."

Up to half of patients with chronic rhinosinusitis have comorbid asthma, and Dr. Hulse and her associates at Northwestern University, Chicago, have previously reported that a subset of chronic rhinosinusitis patients with nasal polyps (CRSwNP) have elevated autoantigen-specific antibodies within their nasal polyps (J. Allergy Clin. Immunol. 2011;128:1198-206). In what she said is the first study of its kind, Dr. Hulse of the school’s division of allergy and immunology, and her associates retrospectively reviewed a database of 1,240 patients who underwent nasal surgery or were treated for CRS at Northwestern. They evaluated the effect of gender on the prevalence of CRSwNP, aspirin sensitivity, and asthma status, and used enzyme-linked immunosorbent assay to compare levels of eosinophil cationic protein and anti-dsDNA antibodies in NP extracts from men and women.

Mean patient age was 41 years, and 48% were women. Although women comprised about 50% of controls and CRS patients without NP, a significantly smaller proportion of CRSwNP patients were female (35%). Women with CRSwNP were significantly more likely to have comorbid asthma, and 65% of patients with aspirin-exacerbated respiratory disease (CRSwNP plus asthma and aspirin sensitivity) were women. Asthmatic women with CRSwNP had the highest levels of autoantigen-specific IgG and eosinophil cationic protein, and were significantly more likely to have revision surgeries.

"We thought we would find that CRSwNP was more prevalent and severe in women, especially because these patients have asthma and some features of local autoimmunity, which can be more prevalent and severe in women," Dr. Hulse said. "Instead, we found that men were more likely to have CRSwNP than women, but women did seem to have more severe disease."

She acknowledged certain limitations of the study, including the fact that it focused solely on patients receiving care at a tertiary care center, "so we do not know if these results would be similar if we looked at the general population of people with CRSwNP who do not seek out specialized care. Also, these data were collected for patients at only one location, so we also do not know if the results would be similar at other tertiary care centers."

During a press briefing at the meeting, Dr. Hulse characterized the findings as "an important first step in identifying a potential area of future research and providing the justification for doing larger studies to see if this holds true in a larger population [of patients] or at other sites."

The study was funded by grants from the National Institutes of Health, including the Building Interdisciplinary Research Careers in Women’s Health program. Dr. Hulse said that she had no relevant financial conflicts.

dbrunk@frontlinemedcom.com

SAN DIEGO – Women with chronic rhinosinusitis and co-occurring nasal polyps appear to harbor more severe disease, compared with men, results from a large retrospective study demonstrate.

"For now, these are very preliminary studies, so there is not a lot of clinical application," Kathryn E. Hulse, Ph.D., said in an interview before the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the work was presented. "The hope is that if we can figure out why chronic rhinosinusitis with nasal polyps is more severe in women, we would be able to design better therapeutic strategies to treat this disease in both men and women."

Up to half of patients with chronic rhinosinusitis have comorbid asthma, and Dr. Hulse and her associates at Northwestern University, Chicago, have previously reported that a subset of chronic rhinosinusitis patients with nasal polyps (CRSwNP) have elevated autoantigen-specific antibodies within their nasal polyps (J. Allergy Clin. Immunol. 2011;128:1198-206). In what she said is the first study of its kind, Dr. Hulse of the school’s division of allergy and immunology, and her associates retrospectively reviewed a database of 1,240 patients who underwent nasal surgery or were treated for CRS at Northwestern. They evaluated the effect of gender on the prevalence of CRSwNP, aspirin sensitivity, and asthma status, and used enzyme-linked immunosorbent assay to compare levels of eosinophil cationic protein and anti-dsDNA antibodies in NP extracts from men and women.

Mean patient age was 41 years, and 48% were women. Although women comprised about 50% of controls and CRS patients without NP, a significantly smaller proportion of CRSwNP patients were female (35%). Women with CRSwNP were significantly more likely to have comorbid asthma, and 65% of patients with aspirin-exacerbated respiratory disease (CRSwNP plus asthma and aspirin sensitivity) were women. Asthmatic women with CRSwNP had the highest levels of autoantigen-specific IgG and eosinophil cationic protein, and were significantly more likely to have revision surgeries.

"We thought we would find that CRSwNP was more prevalent and severe in women, especially because these patients have asthma and some features of local autoimmunity, which can be more prevalent and severe in women," Dr. Hulse said. "Instead, we found that men were more likely to have CRSwNP than women, but women did seem to have more severe disease."

She acknowledged certain limitations of the study, including the fact that it focused solely on patients receiving care at a tertiary care center, "so we do not know if these results would be similar if we looked at the general population of people with CRSwNP who do not seek out specialized care. Also, these data were collected for patients at only one location, so we also do not know if the results would be similar at other tertiary care centers."

During a press briefing at the meeting, Dr. Hulse characterized the findings as "an important first step in identifying a potential area of future research and providing the justification for doing larger studies to see if this holds true in a larger population [of patients] or at other sites."

The study was funded by grants from the National Institutes of Health, including the Building Interdisciplinary Research Careers in Women’s Health program. Dr. Hulse said that she had no relevant financial conflicts.

dbrunk@frontlinemedcom.com

SAN DIEGO – During 20 months of follow-up, the diagnosis of penicillin "allergy" in hospitalized patients was associated with 10% more total hospital days and a spike in Clostridium difficile and other infections, a large 3-year study demonstrated.

"Based on other work, penicillin ‘allergy’ is inaccurate about 95% of the time," Dr. Eric M. Macy said in an interview prior to the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the work was presented. "More penicillin allergy testing of hospitalized individuals with a history of penicillin ‘allergy’ to document true penicillin allergy has the potential to reduce hospital days and serious infection prevalence," he said.

In an effort to determine hospital utilization and prevalence rates of Clostridium difficile, methicillin resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in patients with and without penicillin allergy, the researchers conducted a retrospective, matched cohort study of 51,807 individuals admitted to Kaiser Foundation hospitals in Southern California during 2010-2012 out of about 3.2 million health plan members, a sample that represents about 1% of the United States population.

Dr. Macy and his associates matched 51,582 of the individuals (99.6% of all cases) to two unique control subjects without an active penicillin allergy. Cases and controls were matched by category for discharge diagnosis, sex, age, and date of admission.

Over the 3-year study period, the penicillin allergic cases averaged 0.59 (9.9%) more total hospital days during 20 months of follow-up, compared with controls. Cases were treated with significantly more fluoroquinolones, clindamycin, and vancomycin, compared with controls (P less than .0001), and cases had 30.1% more VRE infections, 23.4% more C. diff. infections, and 14.1% more MRSA than expected, compared with controls, reported Dr. Macy of the Southern California Permanente Medical Group, San Diego.

When the researchers controlled for the number of drug allergies, differences between cases and controls disappeared. Overall, Dr. Macy and his associates observed a strong positive correlation for all four outcome variables and increasing drug allergy number in both cases and controls.

"This is the largest study ever done looking at the influence of a history of penicillin allergy, hospital utilization, and serious infection prevalence," Dr. Macy remarked. "This type of study could not be done any better." Full findings appear in the March 2014 issue of the Journal of Allergy and Clinical Immunology.

The study was supported by the Kaiser Permanente Health Care Program and by ALK-Abelló, a Danish company that sells an essential penicillin skin test reagent called Pre-Pen. Dr. Macy said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – During 20 months of follow-up, the diagnosis of penicillin "allergy" in hospitalized patients was associated with 10% more total hospital days and a spike in Clostridium difficile and other infections, a large 3-year study demonstrated.

"Based on other work, penicillin ‘allergy’ is inaccurate about 95% of the time," Dr. Eric M. Macy said in an interview prior to the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the work was presented. "More penicillin allergy testing of hospitalized individuals with a history of penicillin ‘allergy’ to document true penicillin allergy has the potential to reduce hospital days and serious infection prevalence," he said.

In an effort to determine hospital utilization and prevalence rates of Clostridium difficile, methicillin resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in patients with and without penicillin allergy, the researchers conducted a retrospective, matched cohort study of 51,807 individuals admitted to Kaiser Foundation hospitals in Southern California during 2010-2012 out of about 3.2 million health plan members, a sample that represents about 1% of the United States population.

Dr. Macy and his associates matched 51,582 of the individuals (99.6% of all cases) to two unique control subjects without an active penicillin allergy. Cases and controls were matched by category for discharge diagnosis, sex, age, and date of admission.

Over the 3-year study period, the penicillin allergic cases averaged 0.59 (9.9%) more total hospital days during 20 months of follow-up, compared with controls. Cases were treated with significantly more fluoroquinolones, clindamycin, and vancomycin, compared with controls (P less than .0001), and cases had 30.1% more VRE infections, 23.4% more C. diff. infections, and 14.1% more MRSA than expected, compared with controls, reported Dr. Macy of the Southern California Permanente Medical Group, San Diego.

When the researchers controlled for the number of drug allergies, differences between cases and controls disappeared. Overall, Dr. Macy and his associates observed a strong positive correlation for all four outcome variables and increasing drug allergy number in both cases and controls.

"This is the largest study ever done looking at the influence of a history of penicillin allergy, hospital utilization, and serious infection prevalence," Dr. Macy remarked. "This type of study could not be done any better." Full findings appear in the March 2014 issue of the Journal of Allergy and Clinical Immunology.

The study was supported by the Kaiser Permanente Health Care Program and by ALK-Abelló, a Danish company that sells an essential penicillin skin test reagent called Pre-Pen. Dr. Macy said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – During 20 months of follow-up, the diagnosis of penicillin "allergy" in hospitalized patients was associated with 10% more total hospital days and a spike in Clostridium difficile and other infections, a large 3-year study demonstrated.

"Based on other work, penicillin ‘allergy’ is inaccurate about 95% of the time," Dr. Eric M. Macy said in an interview prior to the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the work was presented. "More penicillin allergy testing of hospitalized individuals with a history of penicillin ‘allergy’ to document true penicillin allergy has the potential to reduce hospital days and serious infection prevalence," he said.

In an effort to determine hospital utilization and prevalence rates of Clostridium difficile, methicillin resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in patients with and without penicillin allergy, the researchers conducted a retrospective, matched cohort study of 51,807 individuals admitted to Kaiser Foundation hospitals in Southern California during 2010-2012 out of about 3.2 million health plan members, a sample that represents about 1% of the United States population.

Dr. Macy and his associates matched 51,582 of the individuals (99.6% of all cases) to two unique control subjects without an active penicillin allergy. Cases and controls were matched by category for discharge diagnosis, sex, age, and date of admission.

Over the 3-year study period, the penicillin allergic cases averaged 0.59 (9.9%) more total hospital days during 20 months of follow-up, compared with controls. Cases were treated with significantly more fluoroquinolones, clindamycin, and vancomycin, compared with controls (P less than .0001), and cases had 30.1% more VRE infections, 23.4% more C. diff. infections, and 14.1% more MRSA than expected, compared with controls, reported Dr. Macy of the Southern California Permanente Medical Group, San Diego.

When the researchers controlled for the number of drug allergies, differences between cases and controls disappeared. Overall, Dr. Macy and his associates observed a strong positive correlation for all four outcome variables and increasing drug allergy number in both cases and controls.

"This is the largest study ever done looking at the influence of a history of penicillin allergy, hospital utilization, and serious infection prevalence," Dr. Macy remarked. "This type of study could not be done any better." Full findings appear in the March 2014 issue of the Journal of Allergy and Clinical Immunology.

The study was supported by the Kaiser Permanente Health Care Program and by ALK-Abelló, a Danish company that sells an essential penicillin skin test reagent called Pre-Pen. Dr. Macy said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Patients with food allergies – including those with a history of anaphylaxis – had no adverse reactions to propofol administered for anesthesia during endoscopy, based on a study that included 160 patients with food allergies.

Intravenous propofol (2,6-diisopropylphenol) includes lipid suspensions that contain egg lecithin/phosphatide and soy oil, ingredients that have raised "concern regarding administration of propofol in patients with egg and soy allergy," explained Dr. Harshna Mehta, a pediatric allergist-immunologist at the Icahn School of Medicine at Mount Sinai, New York. "Additionally, since the peanut is a legume similar to soy, there is also potential concern for peanut allergic patients."

Case reports of propofol-associated allergic reactions – presumably related to cross-reactivity to foods – have appeared in the medical literature. "However, most of these cases lacked confirmatory testing for actual food allergy vs. mere sensitization," Dr. Mehta said in an interview before the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the study results were presented.

Prior to this study, the largest study included 28 egg allergic patients, with two having a history of anaphylaxis (Anesth. Analg. 2011;113: 140-4).

Dr. Mehta and her associates reviewed the records of 563 patients who had endoscopies performed at the Mount Sinai Center for Eosinophilic Disorders from November 2004 to January 2014.

The researchers identified 160 patients with a median age of 14 years who had one or more food allergies, including 31 with a history of anaphylaxis. Egg, peanut, and soy allergies were confirmed based on finding elevated food specific serum IgE levels, positive skin prick tests and/or convincing allergic reaction history. Patients were included in the study if anesthesia records indicated propofol as the chief anesthetic administered.

Of the 160 patients, 95 had evidence of egg allergy (median egg-IgE = 9.57 kIU/L); 15 of these patients had a history of an anaphylactic reaction to egg. Of the 28 patients with confirmed soy allergy (median soy-IgE = 6.63 kU/L), 2 had a history of anaphylaxis. Dr. Mehta also reported that 117 patients had peanut allergy (median peanut-IgE =38.8 kIU/L); 11 o these patients had a history of anaphylaxis to peanuts.

There were no reported reactions to propofol in any of the patients.

"The most surprising finding was the number of egg/peanut/soy patients who have significant allergic comorbidities – such as history of anaphylaxis, allergic rhinitis, asthma, and atopic disease – that have safely received this medication," Dr. Mehta noted. "We are still in the process of determining the statistical confidence with which we can say how safe propofol is for administration to egg/soy/peanut allergic patients. We are also planning to test the product in the laboratory for the presence of egg protein."

Dr. Mehta said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Patients with food allergies – including those with a history of anaphylaxis – had no adverse reactions to propofol administered for anesthesia during endoscopy, based on a study that included 160 patients with food allergies.

Intravenous propofol (2,6-diisopropylphenol) includes lipid suspensions that contain egg lecithin/phosphatide and soy oil, ingredients that have raised "concern regarding administration of propofol in patients with egg and soy allergy," explained Dr. Harshna Mehta, a pediatric allergist-immunologist at the Icahn School of Medicine at Mount Sinai, New York. "Additionally, since the peanut is a legume similar to soy, there is also potential concern for peanut allergic patients."

Case reports of propofol-associated allergic reactions – presumably related to cross-reactivity to foods – have appeared in the medical literature. "However, most of these cases lacked confirmatory testing for actual food allergy vs. mere sensitization," Dr. Mehta said in an interview before the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the study results were presented.

Prior to this study, the largest study included 28 egg allergic patients, with two having a history of anaphylaxis (Anesth. Analg. 2011;113: 140-4).

Dr. Mehta and her associates reviewed the records of 563 patients who had endoscopies performed at the Mount Sinai Center for Eosinophilic Disorders from November 2004 to January 2014.

The researchers identified 160 patients with a median age of 14 years who had one or more food allergies, including 31 with a history of anaphylaxis. Egg, peanut, and soy allergies were confirmed based on finding elevated food specific serum IgE levels, positive skin prick tests and/or convincing allergic reaction history. Patients were included in the study if anesthesia records indicated propofol as the chief anesthetic administered.

Of the 160 patients, 95 had evidence of egg allergy (median egg-IgE = 9.57 kIU/L); 15 of these patients had a history of an anaphylactic reaction to egg. Of the 28 patients with confirmed soy allergy (median soy-IgE = 6.63 kU/L), 2 had a history of anaphylaxis. Dr. Mehta also reported that 117 patients had peanut allergy (median peanut-IgE =38.8 kIU/L); 11 o these patients had a history of anaphylaxis to peanuts.

There were no reported reactions to propofol in any of the patients.

"The most surprising finding was the number of egg/peanut/soy patients who have significant allergic comorbidities – such as history of anaphylaxis, allergic rhinitis, asthma, and atopic disease – that have safely received this medication," Dr. Mehta noted. "We are still in the process of determining the statistical confidence with which we can say how safe propofol is for administration to egg/soy/peanut allergic patients. We are also planning to test the product in the laboratory for the presence of egg protein."

Dr. Mehta said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Patients with food allergies – including those with a history of anaphylaxis – had no adverse reactions to propofol administered for anesthesia during endoscopy, based on a study that included 160 patients with food allergies.

Intravenous propofol (2,6-diisopropylphenol) includes lipid suspensions that contain egg lecithin/phosphatide and soy oil, ingredients that have raised "concern regarding administration of propofol in patients with egg and soy allergy," explained Dr. Harshna Mehta, a pediatric allergist-immunologist at the Icahn School of Medicine at Mount Sinai, New York. "Additionally, since the peanut is a legume similar to soy, there is also potential concern for peanut allergic patients."

Case reports of propofol-associated allergic reactions – presumably related to cross-reactivity to foods – have appeared in the medical literature. "However, most of these cases lacked confirmatory testing for actual food allergy vs. mere sensitization," Dr. Mehta said in an interview before the annual meeting of the American Academy of Allergy, Asthma, and Immunology, where the study results were presented.

Prior to this study, the largest study included 28 egg allergic patients, with two having a history of anaphylaxis (Anesth. Analg. 2011;113: 140-4).

Dr. Mehta and her associates reviewed the records of 563 patients who had endoscopies performed at the Mount Sinai Center for Eosinophilic Disorders from November 2004 to January 2014.

The researchers identified 160 patients with a median age of 14 years who had one or more food allergies, including 31 with a history of anaphylaxis. Egg, peanut, and soy allergies were confirmed based on finding elevated food specific serum IgE levels, positive skin prick tests and/or convincing allergic reaction history. Patients were included in the study if anesthesia records indicated propofol as the chief anesthetic administered.

Of the 160 patients, 95 had evidence of egg allergy (median egg-IgE = 9.57 kIU/L); 15 of these patients had a history of an anaphylactic reaction to egg. Of the 28 patients with confirmed soy allergy (median soy-IgE = 6.63 kU/L), 2 had a history of anaphylaxis. Dr. Mehta also reported that 117 patients had peanut allergy (median peanut-IgE =38.8 kIU/L); 11 o these patients had a history of anaphylaxis to peanuts.

There were no reported reactions to propofol in any of the patients.

"The most surprising finding was the number of egg/peanut/soy patients who have significant allergic comorbidities – such as history of anaphylaxis, allergic rhinitis, asthma, and atopic disease – that have safely received this medication," Dr. Mehta noted. "We are still in the process of determining the statistical confidence with which we can say how safe propofol is for administration to egg/soy/peanut allergic patients. We are also planning to test the product in the laboratory for the presence of egg protein."

Dr. Mehta said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com