Richard Hyer

CHICAGO – Understanding of the thrombosis risks associated with antiphospholipid syndrome has increased dramatically over the past 12 months, judging from the recent literature on the subject.

Dr. Joan T. Merrill told attendees at a seminar at the Midwest Rheumatology Summit that the annual incidence rate of thrombosis in patients with antiphospholipid antibodies was 1.86% in a prospective multicenter study of 258 patients reported this year (Ann. Rheum. Dis. 2011;70:1083-6).

"Almost 2% per year, and that kind of gets you to 20% at 10 years," said Dr. Merrill. "That’s pretty high, and that’s pretty scary." Hypertension predicts thrombosis, as does the lupus anticoagulant test and lack of thromboprophylaxis during high-risk periods such as post surgery or long airplane flights.

Autoantibodies directed against complement-like structures lead to inflammatory events, including cell-mediated events that lead to a prothrombotic state. "And then, just as you see in atherosclerosis ... when the winds are propitious, what you get is a thrombotic event," said Dr. Merrill, medical director of the Lupus Foundation of America and director of the clinical pharmacology research program at the Oklahoma Medical Research Foundation.

Risk factors for thrombosis are higher in people who have multiple antiphospholipid antibody types (Arthritis Res. Ther. 2011;13:R118). This can be a reason to order multiple tests if insurance providers challenge those tests, said Dr. Merrill. Higher-titer autoantibodies also increase the risk of thrombosis (Acta Obstet. Gynecol. Scand. 2011 July 5 [doi: 10.1111/j.1600-0412. 2011.01236.x]), and antibodies with higher avidity will increase the risk of thrombosis (Lupus 2011;20:1166-71).

The syndrome complicates pregnancy as well.

The odds of women with preeclampsia having anticardiolipin antibodies, versus pregnancy without preeclampsia, were statistically significant (odds ratio, 2.86; 95% confidence interval, 1.37-5.98) in a recent study (Obstet. Gynecol. 2010;116:1433-43), and the odds with severe preeclampsia were much higher (OR, 11.15; CI, 2.66-46.75).

Dr. Merrill advised keeping this increased risk in mind, "since we have lupus patients and we are probably more likely [to order the anticardiolipin screen] than the average obstetrician."

Patients with lupus or antiphospholipid syndrome also often have migraines, and a 2011 study found that patients with a history of migraines have increased thrombotic risk (J. Thromb. Haemost. 2011;9:1350-4). Dr. Merrill advised being aware that what appears to be a migraine in a patient with the antiphospholipid antibody might actually be a thrombotic event, especially if the patient is a young woman.

Significant barriers still exist to evidence-based recommendations, according to information presented last year at the 13th International Congress on Antiphospholipid Antibodies. The barriers include poor standardization of tests.

"Around the country, at different labs, you’re going to get different results. In my place in Oklahoma, I may not even be thinking the same people have lupus that you do," said Dr. Merrill.

Other barriers are a poor understanding of pathogenic risk, heterogeneous patients, and studies that are retrospective and not population based.

A case was made at the end of last year for thrombin inhibition in antiphospholipid syndrome (Acta Clin. Croat. 2010;49:469-77). This could be good news for patients, since current univalent thrombin inhibitors are oral agents, which spare the patient the pain of injecting low-molecular-weight heparin. However, low-molecular-weight heparin may be safe long term for patients with the antiphospholipid syndrome (Ann. Rheum. Dis. 2011;70:1652-4).

"There’s been discussion for many years about the role of statins in the antiphospholipid syndrome," said Dr. Merrill. In a laboratory setting, fluvastatin inhibited markers of a prothrombotic state (Ann. Rheum. Dis. 2011;70:675-82). "It doesn’t provide you with the clinical evidence we like to see, but it’s what we have so far," she said.

The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB. Dr. Merrill acknowledged consulting for Human Genome Sciences, Lilly, EMD Serono, GlaxoSmithKline, and Pfizer; receiving grants from Pfizer and Genentech/Roche; and receiving speaker honoraria from Human Genome Sciences/GlaxoSmithKline and Lilly.

CHICAGO – Understanding of the thrombosis risks associated with antiphospholipid syndrome has increased dramatically over the past 12 months, judging from the recent literature on the subject.

Dr. Joan T. Merrill told attendees at a seminar at the Midwest Rheumatology Summit that the annual incidence rate of thrombosis in patients with antiphospholipid antibodies was 1.86% in a prospective multicenter study of 258 patients reported this year (Ann. Rheum. Dis. 2011;70:1083-6).

"Almost 2% per year, and that kind of gets you to 20% at 10 years," said Dr. Merrill. "That’s pretty high, and that’s pretty scary." Hypertension predicts thrombosis, as does the lupus anticoagulant test and lack of thromboprophylaxis during high-risk periods such as post surgery or long airplane flights.

Autoantibodies directed against complement-like structures lead to inflammatory events, including cell-mediated events that lead to a prothrombotic state. "And then, just as you see in atherosclerosis ... when the winds are propitious, what you get is a thrombotic event," said Dr. Merrill, medical director of the Lupus Foundation of America and director of the clinical pharmacology research program at the Oklahoma Medical Research Foundation.

Risk factors for thrombosis are higher in people who have multiple antiphospholipid antibody types (Arthritis Res. Ther. 2011;13:R118). This can be a reason to order multiple tests if insurance providers challenge those tests, said Dr. Merrill. Higher-titer autoantibodies also increase the risk of thrombosis (Acta Obstet. Gynecol. Scand. 2011 July 5 [doi: 10.1111/j.1600-0412. 2011.01236.x]), and antibodies with higher avidity will increase the risk of thrombosis (Lupus 2011;20:1166-71).

The syndrome complicates pregnancy as well.

The odds of women with preeclampsia having anticardiolipin antibodies, versus pregnancy without preeclampsia, were statistically significant (odds ratio, 2.86; 95% confidence interval, 1.37-5.98) in a recent study (Obstet. Gynecol. 2010;116:1433-43), and the odds with severe preeclampsia were much higher (OR, 11.15; CI, 2.66-46.75).

Dr. Merrill advised keeping this increased risk in mind, "since we have lupus patients and we are probably more likely [to order the anticardiolipin screen] than the average obstetrician."

Patients with lupus or antiphospholipid syndrome also often have migraines, and a 2011 study found that patients with a history of migraines have increased thrombotic risk (J. Thromb. Haemost. 2011;9:1350-4). Dr. Merrill advised being aware that what appears to be a migraine in a patient with the antiphospholipid antibody might actually be a thrombotic event, especially if the patient is a young woman.

Significant barriers still exist to evidence-based recommendations, according to information presented last year at the 13th International Congress on Antiphospholipid Antibodies. The barriers include poor standardization of tests.

"Around the country, at different labs, you’re going to get different results. In my place in Oklahoma, I may not even be thinking the same people have lupus that you do," said Dr. Merrill.

Other barriers are a poor understanding of pathogenic risk, heterogeneous patients, and studies that are retrospective and not population based.

A case was made at the end of last year for thrombin inhibition in antiphospholipid syndrome (Acta Clin. Croat. 2010;49:469-77). This could be good news for patients, since current univalent thrombin inhibitors are oral agents, which spare the patient the pain of injecting low-molecular-weight heparin. However, low-molecular-weight heparin may be safe long term for patients with the antiphospholipid syndrome (Ann. Rheum. Dis. 2011;70:1652-4).

"There’s been discussion for many years about the role of statins in the antiphospholipid syndrome," said Dr. Merrill. In a laboratory setting, fluvastatin inhibited markers of a prothrombotic state (Ann. Rheum. Dis. 2011;70:675-82). "It doesn’t provide you with the clinical evidence we like to see, but it’s what we have so far," she said.

The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB. Dr. Merrill acknowledged consulting for Human Genome Sciences, Lilly, EMD Serono, GlaxoSmithKline, and Pfizer; receiving grants from Pfizer and Genentech/Roche; and receiving speaker honoraria from Human Genome Sciences/GlaxoSmithKline and Lilly.

CHICAGO – Understanding of the thrombosis risks associated with antiphospholipid syndrome has increased dramatically over the past 12 months, judging from the recent literature on the subject.

Dr. Joan T. Merrill told attendees at a seminar at the Midwest Rheumatology Summit that the annual incidence rate of thrombosis in patients with antiphospholipid antibodies was 1.86% in a prospective multicenter study of 258 patients reported this year (Ann. Rheum. Dis. 2011;70:1083-6).

"Almost 2% per year, and that kind of gets you to 20% at 10 years," said Dr. Merrill. "That’s pretty high, and that’s pretty scary." Hypertension predicts thrombosis, as does the lupus anticoagulant test and lack of thromboprophylaxis during high-risk periods such as post surgery or long airplane flights.

Autoantibodies directed against complement-like structures lead to inflammatory events, including cell-mediated events that lead to a prothrombotic state. "And then, just as you see in atherosclerosis ... when the winds are propitious, what you get is a thrombotic event," said Dr. Merrill, medical director of the Lupus Foundation of America and director of the clinical pharmacology research program at the Oklahoma Medical Research Foundation.

Risk factors for thrombosis are higher in people who have multiple antiphospholipid antibody types (Arthritis Res. Ther. 2011;13:R118). This can be a reason to order multiple tests if insurance providers challenge those tests, said Dr. Merrill. Higher-titer autoantibodies also increase the risk of thrombosis (Acta Obstet. Gynecol. Scand. 2011 July 5 [doi: 10.1111/j.1600-0412. 2011.01236.x]), and antibodies with higher avidity will increase the risk of thrombosis (Lupus 2011;20:1166-71).

The syndrome complicates pregnancy as well.

The odds of women with preeclampsia having anticardiolipin antibodies, versus pregnancy without preeclampsia, were statistically significant (odds ratio, 2.86; 95% confidence interval, 1.37-5.98) in a recent study (Obstet. Gynecol. 2010;116:1433-43), and the odds with severe preeclampsia were much higher (OR, 11.15; CI, 2.66-46.75).

Dr. Merrill advised keeping this increased risk in mind, "since we have lupus patients and we are probably more likely [to order the anticardiolipin screen] than the average obstetrician."

Patients with lupus or antiphospholipid syndrome also often have migraines, and a 2011 study found that patients with a history of migraines have increased thrombotic risk (J. Thromb. Haemost. 2011;9:1350-4). Dr. Merrill advised being aware that what appears to be a migraine in a patient with the antiphospholipid antibody might actually be a thrombotic event, especially if the patient is a young woman.

Significant barriers still exist to evidence-based recommendations, according to information presented last year at the 13th International Congress on Antiphospholipid Antibodies. The barriers include poor standardization of tests.

"Around the country, at different labs, you’re going to get different results. In my place in Oklahoma, I may not even be thinking the same people have lupus that you do," said Dr. Merrill.

Other barriers are a poor understanding of pathogenic risk, heterogeneous patients, and studies that are retrospective and not population based.

A case was made at the end of last year for thrombin inhibition in antiphospholipid syndrome (Acta Clin. Croat. 2010;49:469-77). This could be good news for patients, since current univalent thrombin inhibitors are oral agents, which spare the patient the pain of injecting low-molecular-weight heparin. However, low-molecular-weight heparin may be safe long term for patients with the antiphospholipid syndrome (Ann. Rheum. Dis. 2011;70:1652-4).

"There’s been discussion for many years about the role of statins in the antiphospholipid syndrome," said Dr. Merrill. In a laboratory setting, fluvastatin inhibited markers of a prothrombotic state (Ann. Rheum. Dis. 2011;70:675-82). "It doesn’t provide you with the clinical evidence we like to see, but it’s what we have so far," she said.

The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB. Dr. Merrill acknowledged consulting for Human Genome Sciences, Lilly, EMD Serono, GlaxoSmithKline, and Pfizer; receiving grants from Pfizer and Genentech/Roche; and receiving speaker honoraria from Human Genome Sciences/GlaxoSmithKline and Lilly.

CHICAGO – Data from two new trials, one in press and the other ongoing, suggest that two established tumor necrosis factor inhibitors may be the safest drugs for treatment of rheumatoid arthritis in a patient with active hepatitis C virus infection.

The recent pilot study (Journal of Hepatology, in press) of 50 patients with coexisting rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection clearly demonstrated that adding etanercept to traditional antiviral therapy was associated with clearing HCV and normalizing liver enzymes, Dr. Leonard H. Calabrese said at the Midwest Rheumatology Summit.

"This was kind of an opening salvo to us, saying, this is our drug. We should be looking at this ... to see if it’s an option to use to treat autoinflammatory disease and, in particular, rheumatoid arthritis," said Dr. Calabrese.

The ongoing Partner Trial is designed to answer the question of whether a tumor necrosis factor (TNF) inhibitor enhances antiviral responses to traditional therapy, specifically the efficacy of infliximab as an adjunct to peginterferon alfa-2b and ribavirin in the treatment of HCV genotype 1.

"One thing that is not a good idea is to use hepatotoxic drugs (like) methotrexate," said Dr. Calabrese.

Treatment is not the only challenge in caring for the patient with overlapping RA and HCV; just making the HCV diagnosis can be difficult.

"The most undiagnosed infection in our country is hepatitis C. There are probably about 3 million people walking around who are infected, who don't know it," said Dr. Calabrese, professor of medicine at the Cleveland Clinic’s Lerner College of Medicine at Case Western Reserve University. Most patients with undiagnosed hepatitis C have chronic infection, which is relatively asymptomatic, he said. "That’s why screening programs are essential."

He described a 49-year-old woman with a history of polyarthritis who presented for evaluation after a 7-month history of migratory arthritis involving feet, hands, wrists, and knees. The patient had a "fairly normal" hemogram and normal alanine transaminase (ALT) and was positive for the anti–cyclic citrullinated peptide (CCP) antibody.

"The most undiagnosed infection in our country is hepatitis C."

"So she clearly has rheumatoid arthritis ... and is an excellent candidate for methotrexate," he said. Lab results showed the woman to be positive for the HCV antibody, and negative for hepatitis B surface antigen and hepatitis B core antibody.

"So the question is, does this patient have active hepatitis C infection?" said Dr. Calabrese. And if so, how would that influence treatment decisions?

Nearly half of patients with chronic HCV have ALTs within the normal range, so the test has no negative predictive value. "The gold standard of diagnosis in HCV is the presence of fibrosis on liver biopsy," said Dr. Calabrese. "The reality is that if you have people with persistently normal ALT levels, upon biopsy, 75% have some evidence of damage, and about a third of them have advanced fibrosis."

This patient was found to have a normal ALT-38 u/mL, to have 1.2 million copies/mL of HCV-RNA, and to have genotype 1. Her liver appeared normal on ultrasound.

This patient has normal ALT but clearly has HCV, he said. "Normal liver enzymes do nothing at this juncture to tell us that this patient does not have a significant problem." While a biopsy is invasive, it has a very acceptable rate of complications, he said.

The alternative to biopsy is the transient elastography test, widely used in Europe. It is noninvasive and accurate, but not yet approved in the United States.

And the 49-year-old woman? "Patients such as this I would treat with a TNF-inhibitor monotherapy, and if that patient needs treatment, or my hepatologist says ‘I want to start this patient on therapy for hepatitis C next month’? Let’s do it – and keep them right on their TNF-inhibitor. We have enough data now to know that it’s probably a safe thing," he said.

Dr. Calabrese disclosed consultant and/or speaking income from Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genentech, Pfizer, and Roche. The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB.

CHICAGO – Data from two new trials, one in press and the other ongoing, suggest that two established tumor necrosis factor inhibitors may be the safest drugs for treatment of rheumatoid arthritis in a patient with active hepatitis C virus infection.

The recent pilot study (Journal of Hepatology, in press) of 50 patients with coexisting rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection clearly demonstrated that adding etanercept to traditional antiviral therapy was associated with clearing HCV and normalizing liver enzymes, Dr. Leonard H. Calabrese said at the Midwest Rheumatology Summit.

"This was kind of an opening salvo to us, saying, this is our drug. We should be looking at this ... to see if it’s an option to use to treat autoinflammatory disease and, in particular, rheumatoid arthritis," said Dr. Calabrese.

The ongoing Partner Trial is designed to answer the question of whether a tumor necrosis factor (TNF) inhibitor enhances antiviral responses to traditional therapy, specifically the efficacy of infliximab as an adjunct to peginterferon alfa-2b and ribavirin in the treatment of HCV genotype 1.

"One thing that is not a good idea is to use hepatotoxic drugs (like) methotrexate," said Dr. Calabrese.

Treatment is not the only challenge in caring for the patient with overlapping RA and HCV; just making the HCV diagnosis can be difficult.

"The most undiagnosed infection in our country is hepatitis C. There are probably about 3 million people walking around who are infected, who don't know it," said Dr. Calabrese, professor of medicine at the Cleveland Clinic’s Lerner College of Medicine at Case Western Reserve University. Most patients with undiagnosed hepatitis C have chronic infection, which is relatively asymptomatic, he said. "That’s why screening programs are essential."

He described a 49-year-old woman with a history of polyarthritis who presented for evaluation after a 7-month history of migratory arthritis involving feet, hands, wrists, and knees. The patient had a "fairly normal" hemogram and normal alanine transaminase (ALT) and was positive for the anti–cyclic citrullinated peptide (CCP) antibody.

"The most undiagnosed infection in our country is hepatitis C."

"So she clearly has rheumatoid arthritis ... and is an excellent candidate for methotrexate," he said. Lab results showed the woman to be positive for the HCV antibody, and negative for hepatitis B surface antigen and hepatitis B core antibody.

"So the question is, does this patient have active hepatitis C infection?" said Dr. Calabrese. And if so, how would that influence treatment decisions?

Nearly half of patients with chronic HCV have ALTs within the normal range, so the test has no negative predictive value. "The gold standard of diagnosis in HCV is the presence of fibrosis on liver biopsy," said Dr. Calabrese. "The reality is that if you have people with persistently normal ALT levels, upon biopsy, 75% have some evidence of damage, and about a third of them have advanced fibrosis."

This patient was found to have a normal ALT-38 u/mL, to have 1.2 million copies/mL of HCV-RNA, and to have genotype 1. Her liver appeared normal on ultrasound.

This patient has normal ALT but clearly has HCV, he said. "Normal liver enzymes do nothing at this juncture to tell us that this patient does not have a significant problem." While a biopsy is invasive, it has a very acceptable rate of complications, he said.

The alternative to biopsy is the transient elastography test, widely used in Europe. It is noninvasive and accurate, but not yet approved in the United States.

And the 49-year-old woman? "Patients such as this I would treat with a TNF-inhibitor monotherapy, and if that patient needs treatment, or my hepatologist says ‘I want to start this patient on therapy for hepatitis C next month’? Let’s do it – and keep them right on their TNF-inhibitor. We have enough data now to know that it’s probably a safe thing," he said.

Dr. Calabrese disclosed consultant and/or speaking income from Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genentech, Pfizer, and Roche. The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB.

CHICAGO – Data from two new trials, one in press and the other ongoing, suggest that two established tumor necrosis factor inhibitors may be the safest drugs for treatment of rheumatoid arthritis in a patient with active hepatitis C virus infection.

The recent pilot study (Journal of Hepatology, in press) of 50 patients with coexisting rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection clearly demonstrated that adding etanercept to traditional antiviral therapy was associated with clearing HCV and normalizing liver enzymes, Dr. Leonard H. Calabrese said at the Midwest Rheumatology Summit.

"This was kind of an opening salvo to us, saying, this is our drug. We should be looking at this ... to see if it’s an option to use to treat autoinflammatory disease and, in particular, rheumatoid arthritis," said Dr. Calabrese.

The ongoing Partner Trial is designed to answer the question of whether a tumor necrosis factor (TNF) inhibitor enhances antiviral responses to traditional therapy, specifically the efficacy of infliximab as an adjunct to peginterferon alfa-2b and ribavirin in the treatment of HCV genotype 1.

"One thing that is not a good idea is to use hepatotoxic drugs (like) methotrexate," said Dr. Calabrese.

Treatment is not the only challenge in caring for the patient with overlapping RA and HCV; just making the HCV diagnosis can be difficult.

"The most undiagnosed infection in our country is hepatitis C. There are probably about 3 million people walking around who are infected, who don't know it," said Dr. Calabrese, professor of medicine at the Cleveland Clinic’s Lerner College of Medicine at Case Western Reserve University. Most patients with undiagnosed hepatitis C have chronic infection, which is relatively asymptomatic, he said. "That’s why screening programs are essential."

He described a 49-year-old woman with a history of polyarthritis who presented for evaluation after a 7-month history of migratory arthritis involving feet, hands, wrists, and knees. The patient had a "fairly normal" hemogram and normal alanine transaminase (ALT) and was positive for the anti–cyclic citrullinated peptide (CCP) antibody.

"The most undiagnosed infection in our country is hepatitis C."

"So she clearly has rheumatoid arthritis ... and is an excellent candidate for methotrexate," he said. Lab results showed the woman to be positive for the HCV antibody, and negative for hepatitis B surface antigen and hepatitis B core antibody.

"So the question is, does this patient have active hepatitis C infection?" said Dr. Calabrese. And if so, how would that influence treatment decisions?

Nearly half of patients with chronic HCV have ALTs within the normal range, so the test has no negative predictive value. "The gold standard of diagnosis in HCV is the presence of fibrosis on liver biopsy," said Dr. Calabrese. "The reality is that if you have people with persistently normal ALT levels, upon biopsy, 75% have some evidence of damage, and about a third of them have advanced fibrosis."

This patient was found to have a normal ALT-38 u/mL, to have 1.2 million copies/mL of HCV-RNA, and to have genotype 1. Her liver appeared normal on ultrasound.

This patient has normal ALT but clearly has HCV, he said. "Normal liver enzymes do nothing at this juncture to tell us that this patient does not have a significant problem." While a biopsy is invasive, it has a very acceptable rate of complications, he said.

The alternative to biopsy is the transient elastography test, widely used in Europe. It is noninvasive and accurate, but not yet approved in the United States.

And the 49-year-old woman? "Patients such as this I would treat with a TNF-inhibitor monotherapy, and if that patient needs treatment, or my hepatologist says ‘I want to start this patient on therapy for hepatitis C next month’? Let’s do it – and keep them right on their TNF-inhibitor. We have enough data now to know that it’s probably a safe thing," he said.

Dr. Calabrese disclosed consultant and/or speaking income from Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genentech, Pfizer, and Roche. The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB.

CHICAGO – The idea that cannabis use might trigger a patient’s first psychotic episode is one that needs to be taken seriously, Dr. John Csernansky said at a seminar on "Reinventing Inpatient Psychiatry."

"Are there patients out there who have schizophrenia who would not have had it without substance abuse? There may be," said Dr. Csernansky, chairman of the department of psychiatry and behavioral sciences at Northwestern University, Chicago. "This is a very hot topic and one that is genuinely frightening."

Cannabis use is frequent within 1-2 years before the first psychotic break. A variety of epidemiological studies suggest that cannabis use in adolescence (15-18) increases the risk for development of schizophrenia, even years later. A meta-analysis published earlier this year (Arch. Gen. Psychiatry 2011;68:555-61) provides evidence of a relationship between cannabis use and earlier onset of psychosis. The meta-analysis, which included data from 83 studies, found that the mean age of psychosis for cannabis users was 2.70 years younger than for nonusers. More than 8,000 patients who reported using psychoactive substances and more than 14,000 who did not were covered by the meta-analysis.

©ron hilton/iStockphoto.com

The connection between cannabis use and early psychosis is particularly concerning because substance abuse is common in schizophrenia. Cannabis, in particular, has a severe effect on the thalamus of the person with schizophrenia. This effect is worse than the effect of alcohol.

"It looks as though alcohol makes schizophrenia worse, whereas cannabis damages a part of the brain that maybe otherwise would have not been [damaged]," Dr. Csernansky said.

If cannabis is used before the first psychotic episode, it "piles on damage," Dr. Csernansky said. A study of a group of prodromal subjects found ventricular volume increased with cannabis abuse and much less with alcohol abuse. Similar relationships were not observed with the use of nicotine.

There may be a familial contribution to the propensity to use drugs on top of severe mental illness, said Dr. Csernansky. When discordant sibling pairs, with and without schizophrenia, were assessed for lifetime history of substance use disorders, the nonpsychotic siblings of schizophrenia patients had higher rates of cannabis and alcohol abuse.

"Something about having [schizophrenia] in your family puts you at risk for more substance abuse," he said.

Dr. Csernansky receives consulting fees as a consultant on the data monitoring committee for Sanofi-Aventis and Eli Lilly.

CHICAGO – The idea that cannabis use might trigger a patient’s first psychotic episode is one that needs to be taken seriously, Dr. John Csernansky said at a seminar on "Reinventing Inpatient Psychiatry."

"Are there patients out there who have schizophrenia who would not have had it without substance abuse? There may be," said Dr. Csernansky, chairman of the department of psychiatry and behavioral sciences at Northwestern University, Chicago. "This is a very hot topic and one that is genuinely frightening."

Cannabis use is frequent within 1-2 years before the first psychotic break. A variety of epidemiological studies suggest that cannabis use in adolescence (15-18) increases the risk for development of schizophrenia, even years later. A meta-analysis published earlier this year (Arch. Gen. Psychiatry 2011;68:555-61) provides evidence of a relationship between cannabis use and earlier onset of psychosis. The meta-analysis, which included data from 83 studies, found that the mean age of psychosis for cannabis users was 2.70 years younger than for nonusers. More than 8,000 patients who reported using psychoactive substances and more than 14,000 who did not were covered by the meta-analysis.

©ron hilton/iStockphoto.com

The connection between cannabis use and early psychosis is particularly concerning because substance abuse is common in schizophrenia. Cannabis, in particular, has a severe effect on the thalamus of the person with schizophrenia. This effect is worse than the effect of alcohol.

"It looks as though alcohol makes schizophrenia worse, whereas cannabis damages a part of the brain that maybe otherwise would have not been [damaged]," Dr. Csernansky said.

If cannabis is used before the first psychotic episode, it "piles on damage," Dr. Csernansky said. A study of a group of prodromal subjects found ventricular volume increased with cannabis abuse and much less with alcohol abuse. Similar relationships were not observed with the use of nicotine.

There may be a familial contribution to the propensity to use drugs on top of severe mental illness, said Dr. Csernansky. When discordant sibling pairs, with and without schizophrenia, were assessed for lifetime history of substance use disorders, the nonpsychotic siblings of schizophrenia patients had higher rates of cannabis and alcohol abuse.

"Something about having [schizophrenia] in your family puts you at risk for more substance abuse," he said.

Dr. Csernansky receives consulting fees as a consultant on the data monitoring committee for Sanofi-Aventis and Eli Lilly.

CHICAGO – The idea that cannabis use might trigger a patient’s first psychotic episode is one that needs to be taken seriously, Dr. John Csernansky said at a seminar on "Reinventing Inpatient Psychiatry."

"Are there patients out there who have schizophrenia who would not have had it without substance abuse? There may be," said Dr. Csernansky, chairman of the department of psychiatry and behavioral sciences at Northwestern University, Chicago. "This is a very hot topic and one that is genuinely frightening."

Cannabis use is frequent within 1-2 years before the first psychotic break. A variety of epidemiological studies suggest that cannabis use in adolescence (15-18) increases the risk for development of schizophrenia, even years later. A meta-analysis published earlier this year (Arch. Gen. Psychiatry 2011;68:555-61) provides evidence of a relationship between cannabis use and earlier onset of psychosis. The meta-analysis, which included data from 83 studies, found that the mean age of psychosis for cannabis users was 2.70 years younger than for nonusers. More than 8,000 patients who reported using psychoactive substances and more than 14,000 who did not were covered by the meta-analysis.

©ron hilton/iStockphoto.com

The connection between cannabis use and early psychosis is particularly concerning because substance abuse is common in schizophrenia. Cannabis, in particular, has a severe effect on the thalamus of the person with schizophrenia. This effect is worse than the effect of alcohol.

"It looks as though alcohol makes schizophrenia worse, whereas cannabis damages a part of the brain that maybe otherwise would have not been [damaged]," Dr. Csernansky said.

If cannabis is used before the first psychotic episode, it "piles on damage," Dr. Csernansky said. A study of a group of prodromal subjects found ventricular volume increased with cannabis abuse and much less with alcohol abuse. Similar relationships were not observed with the use of nicotine.

There may be a familial contribution to the propensity to use drugs on top of severe mental illness, said Dr. Csernansky. When discordant sibling pairs, with and without schizophrenia, were assessed for lifetime history of substance use disorders, the nonpsychotic siblings of schizophrenia patients had higher rates of cannabis and alcohol abuse.

"Something about having [schizophrenia] in your family puts you at risk for more substance abuse," he said.

Dr. Csernansky receives consulting fees as a consultant on the data monitoring committee for Sanofi-Aventis and Eli Lilly.

CHICAGO – A new 29-bed inpatient psychiatric care facility at Northwestern Memorial Hospital’s Stone Institute of Psychiatry was designed with two key elements in mind: the on-stage, off-stage concept, also known as the "Disney concept," and the idea of a treatment mall, said registered nurse Maureen Slade. Above all, the designers wanted patients to feel safe and comfortable, as in a neighborhood.

Photo Richard Hyer/Elsevier Global Medical News

"You can have that philosophy in your head, but if you don’t have a facility that supports that, it’s very hard to actualize the concept," said Ms. Slade, who worked actively on the facility’s design.

The new unit, known as Galter 13 because it is on the 13th floor of the hospital’s Galter Pavilion, is scheduled to open Sept. 24, but was recently previewed in a seminar at the hospital titled "Reinventing Inpatient Psychiatry." The unit includes patient rooms, a day room, group rooms, a gym, a dining room, a meditation/comfort room, and nursing stations.

Patient care occurs in the "on-stage" area, which is available only to those directly caring for or supporting patients. These might include consulting physicians, nursing staff, and environmental services, but not support personnel like pharmacy or materials management. The latter functions will be kept out of sight to maintain patients’ privacy.

Interview rooms allow family, significant others, or outside therapists to meet the staff without having the patient present, or for that matter ever entering the patient’s care space.

Therapeutic groups, structured activities, and community dining occur in one of four areas known as the "treatment mall": the dining room, group room, occupational therapy room, and gym. Programming in the mall occurs all day and into the evening, from 8 a.m. to 9 p.m.

Northwestern hopes that Galter 13’s novel design will create a sense of community, shelter, and comfort that models life: Patient rooms are to be considered home, the day room is the neighborhood, and the treatment mall is to be thought of as "working downtown."

Large glass picture windows protectively sheathed in unbreakable Lexan provide the entire space with ample daylight.

Photo Richard Hyer/Elsevier Global Medical News

"We want the patients ... to come out of their rooms and engage," Ms. Slade said. She hopes the unit’s many offerings will help patients develop skills in self-management.

Technology also is used to enhance care. All group rooms and the meditation/comfort room have monitors for educational DVDs. Special lighting features like atmospheric ceilings change color and brightness with the time of day or night to support the patients’ circadian rhythms.

The small but comfortable meditation/comfort room exists to supply a single patient with a quiet, healing space where even lighting can be individualized in both color and brightness. The room is equipped with various other soothing nuances, including aromatherapy and weighted blankets.

Advanced call and communication systems are made available to the staff.

The facility supports best practices, said Ms. Slade, including expert psychopharmacology, empowering communications like cognitive-behavioral therapy and behavioral activation, and neuromodulation, including transcranial magnetic stimulation, electroconvulsive treatment, and deep brain stimulation.

Most of the patient’s rooms are private, and all are uncluttered and designed for safety. Mirrors are not glass, hinges run the full length of doors, and all fixtures are either encased or are otherwise ligature-resistant. The unit also contains Stryker psychiatric beds without side rails, though patients deemed medically compromised get acute care beds.

"We’re pretty obsessed with safety and security ... we want zero suicides in our unit," Ms. Slade said.

Ms. Slade disclosed no conflicts of interest.

CHICAGO – A new 29-bed inpatient psychiatric care facility at Northwestern Memorial Hospital’s Stone Institute of Psychiatry was designed with two key elements in mind: the on-stage, off-stage concept, also known as the "Disney concept," and the idea of a treatment mall, said registered nurse Maureen Slade. Above all, the designers wanted patients to feel safe and comfortable, as in a neighborhood.

Photo Richard Hyer/Elsevier Global Medical News

"You can have that philosophy in your head, but if you don’t have a facility that supports that, it’s very hard to actualize the concept," said Ms. Slade, who worked actively on the facility’s design.

The new unit, known as Galter 13 because it is on the 13th floor of the hospital’s Galter Pavilion, is scheduled to open Sept. 24, but was recently previewed in a seminar at the hospital titled "Reinventing Inpatient Psychiatry." The unit includes patient rooms, a day room, group rooms, a gym, a dining room, a meditation/comfort room, and nursing stations.

Patient care occurs in the "on-stage" area, which is available only to those directly caring for or supporting patients. These might include consulting physicians, nursing staff, and environmental services, but not support personnel like pharmacy or materials management. The latter functions will be kept out of sight to maintain patients’ privacy.

Interview rooms allow family, significant others, or outside therapists to meet the staff without having the patient present, or for that matter ever entering the patient’s care space.

Therapeutic groups, structured activities, and community dining occur in one of four areas known as the "treatment mall": the dining room, group room, occupational therapy room, and gym. Programming in the mall occurs all day and into the evening, from 8 a.m. to 9 p.m.

Northwestern hopes that Galter 13’s novel design will create a sense of community, shelter, and comfort that models life: Patient rooms are to be considered home, the day room is the neighborhood, and the treatment mall is to be thought of as "working downtown."

Large glass picture windows protectively sheathed in unbreakable Lexan provide the entire space with ample daylight.

Photo Richard Hyer/Elsevier Global Medical News

"We want the patients ... to come out of their rooms and engage," Ms. Slade said. She hopes the unit’s many offerings will help patients develop skills in self-management.

Technology also is used to enhance care. All group rooms and the meditation/comfort room have monitors for educational DVDs. Special lighting features like atmospheric ceilings change color and brightness with the time of day or night to support the patients’ circadian rhythms.

The small but comfortable meditation/comfort room exists to supply a single patient with a quiet, healing space where even lighting can be individualized in both color and brightness. The room is equipped with various other soothing nuances, including aromatherapy and weighted blankets.

Advanced call and communication systems are made available to the staff.

The facility supports best practices, said Ms. Slade, including expert psychopharmacology, empowering communications like cognitive-behavioral therapy and behavioral activation, and neuromodulation, including transcranial magnetic stimulation, electroconvulsive treatment, and deep brain stimulation.

Most of the patient’s rooms are private, and all are uncluttered and designed for safety. Mirrors are not glass, hinges run the full length of doors, and all fixtures are either encased or are otherwise ligature-resistant. The unit also contains Stryker psychiatric beds without side rails, though patients deemed medically compromised get acute care beds.

"We’re pretty obsessed with safety and security ... we want zero suicides in our unit," Ms. Slade said.

Ms. Slade disclosed no conflicts of interest.

CHICAGO – A new 29-bed inpatient psychiatric care facility at Northwestern Memorial Hospital’s Stone Institute of Psychiatry was designed with two key elements in mind: the on-stage, off-stage concept, also known as the "Disney concept," and the idea of a treatment mall, said registered nurse Maureen Slade. Above all, the designers wanted patients to feel safe and comfortable, as in a neighborhood.

Photo Richard Hyer/Elsevier Global Medical News

"You can have that philosophy in your head, but if you don’t have a facility that supports that, it’s very hard to actualize the concept," said Ms. Slade, who worked actively on the facility’s design.

The new unit, known as Galter 13 because it is on the 13th floor of the hospital’s Galter Pavilion, is scheduled to open Sept. 24, but was recently previewed in a seminar at the hospital titled "Reinventing Inpatient Psychiatry." The unit includes patient rooms, a day room, group rooms, a gym, a dining room, a meditation/comfort room, and nursing stations.

Patient care occurs in the "on-stage" area, which is available only to those directly caring for or supporting patients. These might include consulting physicians, nursing staff, and environmental services, but not support personnel like pharmacy or materials management. The latter functions will be kept out of sight to maintain patients’ privacy.

Interview rooms allow family, significant others, or outside therapists to meet the staff without having the patient present, or for that matter ever entering the patient’s care space.

Therapeutic groups, structured activities, and community dining occur in one of four areas known as the "treatment mall": the dining room, group room, occupational therapy room, and gym. Programming in the mall occurs all day and into the evening, from 8 a.m. to 9 p.m.

Northwestern hopes that Galter 13’s novel design will create a sense of community, shelter, and comfort that models life: Patient rooms are to be considered home, the day room is the neighborhood, and the treatment mall is to be thought of as "working downtown."

Large glass picture windows protectively sheathed in unbreakable Lexan provide the entire space with ample daylight.

Photo Richard Hyer/Elsevier Global Medical News

"We want the patients ... to come out of their rooms and engage," Ms. Slade said. She hopes the unit’s many offerings will help patients develop skills in self-management.

Technology also is used to enhance care. All group rooms and the meditation/comfort room have monitors for educational DVDs. Special lighting features like atmospheric ceilings change color and brightness with the time of day or night to support the patients’ circadian rhythms.

The small but comfortable meditation/comfort room exists to supply a single patient with a quiet, healing space where even lighting can be individualized in both color and brightness. The room is equipped with various other soothing nuances, including aromatherapy and weighted blankets.

Advanced call and communication systems are made available to the staff.

The facility supports best practices, said Ms. Slade, including expert psychopharmacology, empowering communications like cognitive-behavioral therapy and behavioral activation, and neuromodulation, including transcranial magnetic stimulation, electroconvulsive treatment, and deep brain stimulation.

Most of the patient’s rooms are private, and all are uncluttered and designed for safety. Mirrors are not glass, hinges run the full length of doors, and all fixtures are either encased or are otherwise ligature-resistant. The unit also contains Stryker psychiatric beds without side rails, though patients deemed medically compromised get acute care beds.

"We’re pretty obsessed with safety and security ... we want zero suicides in our unit," Ms. Slade said.

Ms. Slade disclosed no conflicts of interest.

CHICAGO – Schizophrenia, bipolar disorder, and major depressive disorder all benefit from early diagnosis and aggressive therapy, and the new First Contact program at Northwestern Memorial Hospital is an attempt to provide it to all three disorders in an orderly way.

"A seamless integration of patient care from the very beginning" is how it was described by Dr. Will Cronenwett, medical director of outpatient psychiatry at Northwestern Memorial Hospital’s Stone Institute of Psychiatry in Chicago. Dr. Cronenwett outlined First Contact in a hospital seminar titled "Reinventing Inpatient Psychiatry."

In the conventional model of care, the prodromes of schizophrenia, bipolar disorder, or depression were each seen as a precursor to that particular illness. Patients were recruited based on the risk of the illness, and treatment and disease progression were studied in that light, according to Dr. Cronenwett’s presentation.

The First Contact model, by contrast, is a clinical staging model dependent on time, and not on predicted illness, said Dr. Cronenwett.

"It’s dependent on somebody’s index presentation. ... Either they’ve identified themselves ... or somebody else has talked to them about getting help," he said. Prospective patients may appear healthy because the program intends to get them as early as possible in the course of the illness, ideally within a year of disease onset.

"Our point is to look at this as a staging model, as opposed to a model where we understand specifically where people are headed," said Dr. Cronenwett.

The First Contact program has three dimensions: clinical, research, and outreach. The treatment goals are symptom relief; education and empowerment; and support for role functioning. A specialized early intervention program is core to First Contact, as are coordinated inpatient and outpatient services. The treatment team will be multidisciplinary and will include community outreach. Cognitive behavioral therapy will be incorporated because it is considered effective for mood symptoms and psychosis in early phases of illness (J. Clin. Psychiatry 2009;70:1206-12). The program’s goals include improving the patient’s adaptation to the illness and increasing their subjective quality of life. Self-management will therefore be stressed, as will cognitive enhancement therapy.

The patient, family, and caregiver will all be educated in the program’s goals.

Research will also be integrated into the First Contact program, seeking disease markers via imaging, genetics, and cognitive changes. Outreach will be used to increase public awareness, promote early self-detection, and encourage early referrals. Dr. Cronenwett said there is evidence, although inconclusive, that early therapy reduces the duration of untreated illness (Acta Psychiatr. Scand. 2008;117:440-8).

Ultimately, Northwestern hopes to create and share guidelines for treatment of these illnesses.

None of this will be easy. In the initial phases, all of these illnesses are difficult to identify with accuracy. The first diagnoses, before the disease prodrome, are often unstable, especially for psychosis, but also for bipolar disease.

"Most people identified as prodromal don’t end up converting to psychosis," said Dr. Cronenwett (Am. J. Psychiatry 2011;168:800-5).

In this particular study, only 35% converted to psychosis, whereas 24% remitted completely. Other diagnoses – including anxiety disorder, depression, mania, and substance use disorder – also remitted over time.

He went on to say that the schizophrenia prodrome is a complicated clinical picture, and that the initial presentation does not predict the outcome. "Schizophrenia prodrome has been the most studied phenomenon to date," he said. "Oftentimes the first symptomatic presentation for what later gets diagnosed as schizophrenia is depression."

The bipolar prodrome, with its age of onset at 0-6 years, can present with any number of characteristics, including "stubborn" and "overly sensitive."

"The bipolar prodrome is probably more confusing than schizophrenia," said Dr. Cronenwett. The most common clinical elements are depressed or elevated mood, anger, perceptual changes, energy changes, functional impairment (Bipolar Disord. 2008;10:555-65). He said it may be 10 years between presenting symptoms and final diagnosis . Major depressive disorder is the least-studied prodrome, and overlaps with other prodromal phenomena, he said.

Dr. Cronenwett disclosed research support from Novartis and from Sunovion Pharmaceuticals.

CHICAGO – Schizophrenia, bipolar disorder, and major depressive disorder all benefit from early diagnosis and aggressive therapy, and the new First Contact program at Northwestern Memorial Hospital is an attempt to provide it to all three disorders in an orderly way.

"A seamless integration of patient care from the very beginning" is how it was described by Dr. Will Cronenwett, medical director of outpatient psychiatry at Northwestern Memorial Hospital’s Stone Institute of Psychiatry in Chicago. Dr. Cronenwett outlined First Contact in a hospital seminar titled "Reinventing Inpatient Psychiatry."

In the conventional model of care, the prodromes of schizophrenia, bipolar disorder, or depression were each seen as a precursor to that particular illness. Patients were recruited based on the risk of the illness, and treatment and disease progression were studied in that light, according to Dr. Cronenwett’s presentation.

The First Contact model, by contrast, is a clinical staging model dependent on time, and not on predicted illness, said Dr. Cronenwett.

"It’s dependent on somebody’s index presentation. ... Either they’ve identified themselves ... or somebody else has talked to them about getting help," he said. Prospective patients may appear healthy because the program intends to get them as early as possible in the course of the illness, ideally within a year of disease onset.

"Our point is to look at this as a staging model, as opposed to a model where we understand specifically where people are headed," said Dr. Cronenwett.

The First Contact program has three dimensions: clinical, research, and outreach. The treatment goals are symptom relief; education and empowerment; and support for role functioning. A specialized early intervention program is core to First Contact, as are coordinated inpatient and outpatient services. The treatment team will be multidisciplinary and will include community outreach. Cognitive behavioral therapy will be incorporated because it is considered effective for mood symptoms and psychosis in early phases of illness (J. Clin. Psychiatry 2009;70:1206-12). The program’s goals include improving the patient’s adaptation to the illness and increasing their subjective quality of life. Self-management will therefore be stressed, as will cognitive enhancement therapy.

The patient, family, and caregiver will all be educated in the program’s goals.

Research will also be integrated into the First Contact program, seeking disease markers via imaging, genetics, and cognitive changes. Outreach will be used to increase public awareness, promote early self-detection, and encourage early referrals. Dr. Cronenwett said there is evidence, although inconclusive, that early therapy reduces the duration of untreated illness (Acta Psychiatr. Scand. 2008;117:440-8).

Ultimately, Northwestern hopes to create and share guidelines for treatment of these illnesses.

None of this will be easy. In the initial phases, all of these illnesses are difficult to identify with accuracy. The first diagnoses, before the disease prodrome, are often unstable, especially for psychosis, but also for bipolar disease.

"Most people identified as prodromal don’t end up converting to psychosis," said Dr. Cronenwett (Am. J. Psychiatry 2011;168:800-5).

In this particular study, only 35% converted to psychosis, whereas 24% remitted completely. Other diagnoses – including anxiety disorder, depression, mania, and substance use disorder – also remitted over time.

He went on to say that the schizophrenia prodrome is a complicated clinical picture, and that the initial presentation does not predict the outcome. "Schizophrenia prodrome has been the most studied phenomenon to date," he said. "Oftentimes the first symptomatic presentation for what later gets diagnosed as schizophrenia is depression."

The bipolar prodrome, with its age of onset at 0-6 years, can present with any number of characteristics, including "stubborn" and "overly sensitive."

"The bipolar prodrome is probably more confusing than schizophrenia," said Dr. Cronenwett. The most common clinical elements are depressed or elevated mood, anger, perceptual changes, energy changes, functional impairment (Bipolar Disord. 2008;10:555-65). He said it may be 10 years between presenting symptoms and final diagnosis . Major depressive disorder is the least-studied prodrome, and overlaps with other prodromal phenomena, he said.

Dr. Cronenwett disclosed research support from Novartis and from Sunovion Pharmaceuticals.

CHICAGO – Schizophrenia, bipolar disorder, and major depressive disorder all benefit from early diagnosis and aggressive therapy, and the new First Contact program at Northwestern Memorial Hospital is an attempt to provide it to all three disorders in an orderly way.

"A seamless integration of patient care from the very beginning" is how it was described by Dr. Will Cronenwett, medical director of outpatient psychiatry at Northwestern Memorial Hospital’s Stone Institute of Psychiatry in Chicago. Dr. Cronenwett outlined First Contact in a hospital seminar titled "Reinventing Inpatient Psychiatry."

In the conventional model of care, the prodromes of schizophrenia, bipolar disorder, or depression were each seen as a precursor to that particular illness. Patients were recruited based on the risk of the illness, and treatment and disease progression were studied in that light, according to Dr. Cronenwett’s presentation.

The First Contact model, by contrast, is a clinical staging model dependent on time, and not on predicted illness, said Dr. Cronenwett.

"It’s dependent on somebody’s index presentation. ... Either they’ve identified themselves ... or somebody else has talked to them about getting help," he said. Prospective patients may appear healthy because the program intends to get them as early as possible in the course of the illness, ideally within a year of disease onset.

"Our point is to look at this as a staging model, as opposed to a model where we understand specifically where people are headed," said Dr. Cronenwett.

The First Contact program has three dimensions: clinical, research, and outreach. The treatment goals are symptom relief; education and empowerment; and support for role functioning. A specialized early intervention program is core to First Contact, as are coordinated inpatient and outpatient services. The treatment team will be multidisciplinary and will include community outreach. Cognitive behavioral therapy will be incorporated because it is considered effective for mood symptoms and psychosis in early phases of illness (J. Clin. Psychiatry 2009;70:1206-12). The program’s goals include improving the patient’s adaptation to the illness and increasing their subjective quality of life. Self-management will therefore be stressed, as will cognitive enhancement therapy.

The patient, family, and caregiver will all be educated in the program’s goals.

Research will also be integrated into the First Contact program, seeking disease markers via imaging, genetics, and cognitive changes. Outreach will be used to increase public awareness, promote early self-detection, and encourage early referrals. Dr. Cronenwett said there is evidence, although inconclusive, that early therapy reduces the duration of untreated illness (Acta Psychiatr. Scand. 2008;117:440-8).

Ultimately, Northwestern hopes to create and share guidelines for treatment of these illnesses.

None of this will be easy. In the initial phases, all of these illnesses are difficult to identify with accuracy. The first diagnoses, before the disease prodrome, are often unstable, especially for psychosis, but also for bipolar disease.

"Most people identified as prodromal don’t end up converting to psychosis," said Dr. Cronenwett (Am. J. Psychiatry 2011;168:800-5).

In this particular study, only 35% converted to psychosis, whereas 24% remitted completely. Other diagnoses – including anxiety disorder, depression, mania, and substance use disorder – also remitted over time.

He went on to say that the schizophrenia prodrome is a complicated clinical picture, and that the initial presentation does not predict the outcome. "Schizophrenia prodrome has been the most studied phenomenon to date," he said. "Oftentimes the first symptomatic presentation for what later gets diagnosed as schizophrenia is depression."

The bipolar prodrome, with its age of onset at 0-6 years, can present with any number of characteristics, including "stubborn" and "overly sensitive."

"The bipolar prodrome is probably more confusing than schizophrenia," said Dr. Cronenwett. The most common clinical elements are depressed or elevated mood, anger, perceptual changes, energy changes, functional impairment (Bipolar Disord. 2008;10:555-65). He said it may be 10 years between presenting symptoms and final diagnosis . Major depressive disorder is the least-studied prodrome, and overlaps with other prodromal phenomena, he said.

Dr. Cronenwett disclosed research support from Novartis and from Sunovion Pharmaceuticals.

CHICAGO – Both the psychiatric patient and the medical patient with comorbid psychiatric conditions can be treated with a technique known as behavioral action communication.

"The challenge is ... to immerse the patient in a rich, evidence-based milieu that reinforces goal-directed behavior," said Jacqueline Gollan, Ph.D., director of the Translational Stress and Depression Laboratory at Northwestern University. The concept of behavioral activation is complex, said Dr. Gollan, but broadly invites the patient to reflect on her own behavior or inactivity in various contexts and to reinforce active, positive behaviors. On seeing the latter, "The staff can turn to the patient and say, ‘That’s great. Let’s see if you can do that again.’ "

The goals are to accelerate recovery, independence, and functionality, Dr. Gollan said at a seminar, "Reinventing Inpatient Psychiatry." In a well-controlled context, inpatients can actually learn how to manage their illnesses.

Passivity and avoidance are prevalent in psychiatric conditions, and this behavioral strategy is designed to reduce them, and to improve the quality and acceptability of care, she said.

Theoretically, overall health outcomes will also be improved. The psychiatric concept of avoidance has been linked in the literature to increased hypertension and cardiovascular mortality and diminished immunity, as well as substance abuse, depressive symptoms, overall lower quality of life, and increased mortality, she said.

Northwestern Memorial Hospital integrates behavioral action communication throughout the psychiatric unit, employing it in group meetings, education, nursing care, physician inquiry, discharge plans, and social work. A manual on the subject is given to each patient’s family members so they can reinforce goals at home, helping the individual to identify and reduce passivity and avoidance, and to understand that all behaviors have a purpose or goal. The intent is to teach the patient to connect context, behavior, and mood.

In the clinic, the first step in teaching the psychiatric patient to monitor his or her behavior is a self-reported instrument called the Checklist of Unit Behaviors, or CUB. This checklist assesses the patient’s activation (activities that create positive changes in symptoms or function) in two dimensions: approach and avoidance. The patient and staff members track progress each day with an item-by-item discussion that focuses on the patient’s successes. The conversations emphasize the context and function of behavior; avoidance behaviors are associated with negative affect.

"Every morning, they fill out a CUB," Dr. Gollan said. "It truly reflects what they’re doing. The patient reports being high or low on avoidance or approach. A set of avoidance behaviors is associated with negative affect. On intake you see high levels of avoidance ... then there’s feathering out."

The psychometric properties of the CUB allow clinicians to implement a treatment plan that increases positive affect, ultimately to help the patient have a greater interest in taking care of himself, said Dr. Gollan.

An experiment comparing the behavioral action communication (BAC) unit with the Treatment as Usual (TAU) unit reinforced this finding. Outcome measures were the Brief Symptom Inventory, Positive and Negative Affect Schedule (PANAS), Behavioral Inhibition/Activation Scale (BIS/BAS), and CUB.

The sample (n = 149) was divided between the BAC unit (72 patients) and TAU unit (77 patients), with the TAU acting as the control. No significant differences were found in patient age (mean = 38.7 years) or gender (49% male). A One-Sample T test did not reveal significant differences across psychiatric disorders using Brief Symptom Inventory for each unit at admission (P = .30). These disorders/behaviors included depression, anxiety, hostility, somatization, obsessive-compulsive, interpersonal sensitivity, phobic anxiety, paranoid ideation, and psychoticism.

The study found that increase in positive affect from admission to discharge was higher for those in the BAC unit. Patients in the BAC unit with elevated major depressive disorder reported improved positive affect at discharge, compared with those in the TAU unit. BAC unit patients also reported significantly higher approach behaviors at discharge than did TAU unit patients. BAC and TAU unit patients showed major reduction of avoidance equivalent across units at intake and discharge.

Overall, patients’ assessments of behavioral activation communication were positive. Their comments included: "It helps me visualize what’s going on," "It helps me to write things down instead of just thinking about them," and "It’s nice to know that someone is checking up on you and monitoring your progress."

A member of the audience asked whether the hospital had seen any change in repeat admissions. Dr. Gollan said data on repeat admissions were not yet available.

Dr. Gollan disclosed no relevant conflicts of interest.

CHICAGO – Both the psychiatric patient and the medical patient with comorbid psychiatric conditions can be treated with a technique known as behavioral action communication.

"The challenge is ... to immerse the patient in a rich, evidence-based milieu that reinforces goal-directed behavior," said Jacqueline Gollan, Ph.D., director of the Translational Stress and Depression Laboratory at Northwestern University. The concept of behavioral activation is complex, said Dr. Gollan, but broadly invites the patient to reflect on her own behavior or inactivity in various contexts and to reinforce active, positive behaviors. On seeing the latter, "The staff can turn to the patient and say, ‘That’s great. Let’s see if you can do that again.’ "

The goals are to accelerate recovery, independence, and functionality, Dr. Gollan said at a seminar, "Reinventing Inpatient Psychiatry." In a well-controlled context, inpatients can actually learn how to manage their illnesses.

Passivity and avoidance are prevalent in psychiatric conditions, and this behavioral strategy is designed to reduce them, and to improve the quality and acceptability of care, she said.

Theoretically, overall health outcomes will also be improved. The psychiatric concept of avoidance has been linked in the literature to increased hypertension and cardiovascular mortality and diminished immunity, as well as substance abuse, depressive symptoms, overall lower quality of life, and increased mortality, she said.

Northwestern Memorial Hospital integrates behavioral action communication throughout the psychiatric unit, employing it in group meetings, education, nursing care, physician inquiry, discharge plans, and social work. A manual on the subject is given to each patient’s family members so they can reinforce goals at home, helping the individual to identify and reduce passivity and avoidance, and to understand that all behaviors have a purpose or goal. The intent is to teach the patient to connect context, behavior, and mood.

In the clinic, the first step in teaching the psychiatric patient to monitor his or her behavior is a self-reported instrument called the Checklist of Unit Behaviors, or CUB. This checklist assesses the patient’s activation (activities that create positive changes in symptoms or function) in two dimensions: approach and avoidance. The patient and staff members track progress each day with an item-by-item discussion that focuses on the patient’s successes. The conversations emphasize the context and function of behavior; avoidance behaviors are associated with negative affect.

"Every morning, they fill out a CUB," Dr. Gollan said. "It truly reflects what they’re doing. The patient reports being high or low on avoidance or approach. A set of avoidance behaviors is associated with negative affect. On intake you see high levels of avoidance ... then there’s feathering out."

The psychometric properties of the CUB allow clinicians to implement a treatment plan that increases positive affect, ultimately to help the patient have a greater interest in taking care of himself, said Dr. Gollan.

An experiment comparing the behavioral action communication (BAC) unit with the Treatment as Usual (TAU) unit reinforced this finding. Outcome measures were the Brief Symptom Inventory, Positive and Negative Affect Schedule (PANAS), Behavioral Inhibition/Activation Scale (BIS/BAS), and CUB.

The sample (n = 149) was divided between the BAC unit (72 patients) and TAU unit (77 patients), with the TAU acting as the control. No significant differences were found in patient age (mean = 38.7 years) or gender (49% male). A One-Sample T test did not reveal significant differences across psychiatric disorders using Brief Symptom Inventory for each unit at admission (P = .30). These disorders/behaviors included depression, anxiety, hostility, somatization, obsessive-compulsive, interpersonal sensitivity, phobic anxiety, paranoid ideation, and psychoticism.

The study found that increase in positive affect from admission to discharge was higher for those in the BAC unit. Patients in the BAC unit with elevated major depressive disorder reported improved positive affect at discharge, compared with those in the TAU unit. BAC unit patients also reported significantly higher approach behaviors at discharge than did TAU unit patients. BAC and TAU unit patients showed major reduction of avoidance equivalent across units at intake and discharge.

Overall, patients’ assessments of behavioral activation communication were positive. Their comments included: "It helps me visualize what’s going on," "It helps me to write things down instead of just thinking about them," and "It’s nice to know that someone is checking up on you and monitoring your progress."

A member of the audience asked whether the hospital had seen any change in repeat admissions. Dr. Gollan said data on repeat admissions were not yet available.

Dr. Gollan disclosed no relevant conflicts of interest.

CHICAGO – Both the psychiatric patient and the medical patient with comorbid psychiatric conditions can be treated with a technique known as behavioral action communication.

"The challenge is ... to immerse the patient in a rich, evidence-based milieu that reinforces goal-directed behavior," said Jacqueline Gollan, Ph.D., director of the Translational Stress and Depression Laboratory at Northwestern University. The concept of behavioral activation is complex, said Dr. Gollan, but broadly invites the patient to reflect on her own behavior or inactivity in various contexts and to reinforce active, positive behaviors. On seeing the latter, "The staff can turn to the patient and say, ‘That’s great. Let’s see if you can do that again.’ "

The goals are to accelerate recovery, independence, and functionality, Dr. Gollan said at a seminar, "Reinventing Inpatient Psychiatry." In a well-controlled context, inpatients can actually learn how to manage their illnesses.

Passivity and avoidance are prevalent in psychiatric conditions, and this behavioral strategy is designed to reduce them, and to improve the quality and acceptability of care, she said.

Theoretically, overall health outcomes will also be improved. The psychiatric concept of avoidance has been linked in the literature to increased hypertension and cardiovascular mortality and diminished immunity, as well as substance abuse, depressive symptoms, overall lower quality of life, and increased mortality, she said.

Northwestern Memorial Hospital integrates behavioral action communication throughout the psychiatric unit, employing it in group meetings, education, nursing care, physician inquiry, discharge plans, and social work. A manual on the subject is given to each patient’s family members so they can reinforce goals at home, helping the individual to identify and reduce passivity and avoidance, and to understand that all behaviors have a purpose or goal. The intent is to teach the patient to connect context, behavior, and mood.

In the clinic, the first step in teaching the psychiatric patient to monitor his or her behavior is a self-reported instrument called the Checklist of Unit Behaviors, or CUB. This checklist assesses the patient’s activation (activities that create positive changes in symptoms or function) in two dimensions: approach and avoidance. The patient and staff members track progress each day with an item-by-item discussion that focuses on the patient’s successes. The conversations emphasize the context and function of behavior; avoidance behaviors are associated with negative affect.

"Every morning, they fill out a CUB," Dr. Gollan said. "It truly reflects what they’re doing. The patient reports being high or low on avoidance or approach. A set of avoidance behaviors is associated with negative affect. On intake you see high levels of avoidance ... then there’s feathering out."

The psychometric properties of the CUB allow clinicians to implement a treatment plan that increases positive affect, ultimately to help the patient have a greater interest in taking care of himself, said Dr. Gollan.

An experiment comparing the behavioral action communication (BAC) unit with the Treatment as Usual (TAU) unit reinforced this finding. Outcome measures were the Brief Symptom Inventory, Positive and Negative Affect Schedule (PANAS), Behavioral Inhibition/Activation Scale (BIS/BAS), and CUB.

The sample (n = 149) was divided between the BAC unit (72 patients) and TAU unit (77 patients), with the TAU acting as the control. No significant differences were found in patient age (mean = 38.7 years) or gender (49% male). A One-Sample T test did not reveal significant differences across psychiatric disorders using Brief Symptom Inventory for each unit at admission (P = .30). These disorders/behaviors included depression, anxiety, hostility, somatization, obsessive-compulsive, interpersonal sensitivity, phobic anxiety, paranoid ideation, and psychoticism.

The study found that increase in positive affect from admission to discharge was higher for those in the BAC unit. Patients in the BAC unit with elevated major depressive disorder reported improved positive affect at discharge, compared with those in the TAU unit. BAC unit patients also reported significantly higher approach behaviors at discharge than did TAU unit patients. BAC and TAU unit patients showed major reduction of avoidance equivalent across units at intake and discharge.

Overall, patients’ assessments of behavioral activation communication were positive. Their comments included: "It helps me visualize what’s going on," "It helps me to write things down instead of just thinking about them," and "It’s nice to know that someone is checking up on you and monitoring your progress."

A member of the audience asked whether the hospital had seen any change in repeat admissions. Dr. Gollan said data on repeat admissions were not yet available.

Dr. Gollan disclosed no relevant conflicts of interest.

CHICAGO – The literature is clear that suicide cannot be predicted, but clinicians are obliged to assess it, said Dr. Cathy Frank, vice chair of clinical affairs in the department of psychiatry and behavioral sciences at Northwestern University, Chicago.

There is no perfect algorithm, she said, and no standardized scale is associated with a high predictive value, despite a number of proposals.

And so, most frustrating for the physician is the inability to accurately identify the potential suicide, Dr. Frank said as she reviewed current data on risk assessment and therapy, epidemiology, and risk factors at a seminar on reinventing inpatient psychiatry.

In the United States alone, suicide claims a life every 16 minutes, adding up to 33,300 people annually, compared with 20,000 deaths by homicide, Dr. Frank reported, citing data from the Centers for Disease Control and Prevention.

And, she explained, "It’s not just an illness of industrial populations." Worldwide, 1 million people die from suicide each year, a ratio of 16.7 suicides/100,000 lives (Lancet 2009;373:1372-81).

Nonfatal self-injury is more common in females than males. "Men are three times as likely to complete a suicide ... so gender matters," Dr. Frank said. Patients who have attempted suicide once are five to six times more likely to attempt it again (Arch. Gen. Psychiatry 1983;40:249-57).

Adolescents and young adults are the most likely to attempt suicide, and emergency department data suggest that 75% have a mental disorder and 9% have a diagnosis of alcohol abuse.

There are a variety of social and biological risk factors. Social risk factors include parental separation, family discord, child abuse, bullying, peer victimization, unemployment, living alone, and never having been married.

Physicians and dentists are the occupations most at risk, followed by police officers and military personnel. In 2006, male veterans of the Iraq and Afghanistan wars aged 18-29 years suffered 46 suicides/100,000 lives, a rate 2.3 times higher than in matched civilian population, according to the U.S. Department of Veterans Affairs. The availability of lethal weapons is key risk factor, because 60% of lethal attempts involve firearms. Men are more likely than are women to choose a violent death.

Biological and genetic risk factors have also been identified for suicide. Suicide attempts and completions run in families, independent of psychiatric diagnosis, and adoption studies provide evidence of a genetic basis of, Dr. Frank reported.

"The effectiveness of lithium and clozapine suggests a biological mechanism for suicide," Dr. Frank said. Lithium has both antiaggressive and anti-impulsive effects, she said.

High-risk patients include those with absence of social support, with family conflict, and patients diagnosed with schizophrenia or a mood disorder, along with those who have a history of suicide attempts.

Known markers of acute risk are moderate to severe depression; current mania and/or psychosis; alcohol and/or substance abuse within the last month; hopelessness; and suicidal intent. Markers of moderate risk include mild depression, moderate anxiety, and a history of suicide attempts, as well as chronic pain. Patients at low risk might have anxiety that is neither moderate nor severe, depressive disorder, or bipolar disorder in remission.

Treatment interventions depend on the patient’s mental state, and can range from electroconvulsive therapy and the use of psychotropic medications to straightforward self-management. Self-management is a key to successful treatment, said Dr. Frank, and should begin at admission, making patients active members of the treatment team and letting them help direct the course of treatment.

Family involvement is a particularly essential part of the guidelines and an integral part of treatment, Dr. Frank said. Families "are your eyes and ears." They can provide important collateral information and help assess risk, and family involvement may lower litigation risk. Family conflict, however, has been linked to inpatient suicide (J. Nerv. Ment. Dis. 2010;198:315-28).

The patient’s "community" is now also part of every treatment plan at Dr. Frank’s institution. "No clinician can be everything at all moments to the patient. So how do we involve community?" she said. Community support might include the National Alliance on Mental Illness, Alcoholics Anonymous, Narcotics Anonymous, and bereavement support groups, for example. Dr. Frank also suggests removing weapons from the patient’s home.

Dr. Frank disclosed no relevant conflicts of interest.

CHICAGO – The literature is clear that suicide cannot be predicted, but clinicians are obliged to assess it, said Dr. Cathy Frank, vice chair of clinical affairs in the department of psychiatry and behavioral sciences at Northwestern University, Chicago.

There is no perfect algorithm, she said, and no standardized scale is associated with a high predictive value, despite a number of proposals.

And so, most frustrating for the physician is the inability to accurately identify the potential suicide, Dr. Frank said as she reviewed current data on risk assessment and therapy, epidemiology, and risk factors at a seminar on reinventing inpatient psychiatry.

In the United States alone, suicide claims a life every 16 minutes, adding up to 33,300 people annually, compared with 20,000 deaths by homicide, Dr. Frank reported, citing data from the Centers for Disease Control and Prevention.

And, she explained, "It’s not just an illness of industrial populations." Worldwide, 1 million people die from suicide each year, a ratio of 16.7 suicides/100,000 lives (Lancet 2009;373:1372-81).

Nonfatal self-injury is more common in females than males. "Men are three times as likely to complete a suicide ... so gender matters," Dr. Frank said. Patients who have attempted suicide once are five to six times more likely to attempt it again (Arch. Gen. Psychiatry 1983;40:249-57).

Adolescents and young adults are the most likely to attempt suicide, and emergency department data suggest that 75% have a mental disorder and 9% have a diagnosis of alcohol abuse.

There are a variety of social and biological risk factors. Social risk factors include parental separation, family discord, child abuse, bullying, peer victimization, unemployment, living alone, and never having been married.

Physicians and dentists are the occupations most at risk, followed by police officers and military personnel. In 2006, male veterans of the Iraq and Afghanistan wars aged 18-29 years suffered 46 suicides/100,000 lives, a rate 2.3 times higher than in matched civilian population, according to the U.S. Department of Veterans Affairs. The availability of lethal weapons is key risk factor, because 60% of lethal attempts involve firearms. Men are more likely than are women to choose a violent death.

Biological and genetic risk factors have also been identified for suicide. Suicide attempts and completions run in families, independent of psychiatric diagnosis, and adoption studies provide evidence of a genetic basis of, Dr. Frank reported.

"The effectiveness of lithium and clozapine suggests a biological mechanism for suicide," Dr. Frank said. Lithium has both antiaggressive and anti-impulsive effects, she said.

High-risk patients include those with absence of social support, with family conflict, and patients diagnosed with schizophrenia or a mood disorder, along with those who have a history of suicide attempts.

Known markers of acute risk are moderate to severe depression; current mania and/or psychosis; alcohol and/or substance abuse within the last month; hopelessness; and suicidal intent. Markers of moderate risk include mild depression, moderate anxiety, and a history of suicide attempts, as well as chronic pain. Patients at low risk might have anxiety that is neither moderate nor severe, depressive disorder, or bipolar disorder in remission.

Treatment interventions depend on the patient’s mental state, and can range from electroconvulsive therapy and the use of psychotropic medications to straightforward self-management. Self-management is a key to successful treatment, said Dr. Frank, and should begin at admission, making patients active members of the treatment team and letting them help direct the course of treatment.

Family involvement is a particularly essential part of the guidelines and an integral part of treatment, Dr. Frank said. Families "are your eyes and ears." They can provide important collateral information and help assess risk, and family involvement may lower litigation risk. Family conflict, however, has been linked to inpatient suicide (J. Nerv. Ment. Dis. 2010;198:315-28).

The patient’s "community" is now also part of every treatment plan at Dr. Frank’s institution. "No clinician can be everything at all moments to the patient. So how do we involve community?" she said. Community support might include the National Alliance on Mental Illness, Alcoholics Anonymous, Narcotics Anonymous, and bereavement support groups, for example. Dr. Frank also suggests removing weapons from the patient’s home.

Dr. Frank disclosed no relevant conflicts of interest.

CHICAGO – The literature is clear that suicide cannot be predicted, but clinicians are obliged to assess it, said Dr. Cathy Frank, vice chair of clinical affairs in the department of psychiatry and behavioral sciences at Northwestern University, Chicago.

There is no perfect algorithm, she said, and no standardized scale is associated with a high predictive value, despite a number of proposals.

And so, most frustrating for the physician is the inability to accurately identify the potential suicide, Dr. Frank said as she reviewed current data on risk assessment and therapy, epidemiology, and risk factors at a seminar on reinventing inpatient psychiatry.

In the United States alone, suicide claims a life every 16 minutes, adding up to 33,300 people annually, compared with 20,000 deaths by homicide, Dr. Frank reported, citing data from the Centers for Disease Control and Prevention.

And, she explained, "It’s not just an illness of industrial populations." Worldwide, 1 million people die from suicide each year, a ratio of 16.7 suicides/100,000 lives (Lancet 2009;373:1372-81).

Nonfatal self-injury is more common in females than males. "Men are three times as likely to complete a suicide ... so gender matters," Dr. Frank said. Patients who have attempted suicide once are five to six times more likely to attempt it again (Arch. Gen. Psychiatry 1983;40:249-57).

Adolescents and young adults are the most likely to attempt suicide, and emergency department data suggest that 75% have a mental disorder and 9% have a diagnosis of alcohol abuse.

There are a variety of social and biological risk factors. Social risk factors include parental separation, family discord, child abuse, bullying, peer victimization, unemployment, living alone, and never having been married.

Physicians and dentists are the occupations most at risk, followed by police officers and military personnel. In 2006, male veterans of the Iraq and Afghanistan wars aged 18-29 years suffered 46 suicides/100,000 lives, a rate 2.3 times higher than in matched civilian population, according to the U.S. Department of Veterans Affairs. The availability of lethal weapons is key risk factor, because 60% of lethal attempts involve firearms. Men are more likely than are women to choose a violent death.

Biological and genetic risk factors have also been identified for suicide. Suicide attempts and completions run in families, independent of psychiatric diagnosis, and adoption studies provide evidence of a genetic basis of, Dr. Frank reported.

"The effectiveness of lithium and clozapine suggests a biological mechanism for suicide," Dr. Frank said. Lithium has both antiaggressive and anti-impulsive effects, she said.

High-risk patients include those with absence of social support, with family conflict, and patients diagnosed with schizophrenia or a mood disorder, along with those who have a history of suicide attempts.

Known markers of acute risk are moderate to severe depression; current mania and/or psychosis; alcohol and/or substance abuse within the last month; hopelessness; and suicidal intent. Markers of moderate risk include mild depression, moderate anxiety, and a history of suicide attempts, as well as chronic pain. Patients at low risk might have anxiety that is neither moderate nor severe, depressive disorder, or bipolar disorder in remission.

Treatment interventions depend on the patient’s mental state, and can range from electroconvulsive therapy and the use of psychotropic medications to straightforward self-management. Self-management is a key to successful treatment, said Dr. Frank, and should begin at admission, making patients active members of the treatment team and letting them help direct the course of treatment.

Family involvement is a particularly essential part of the guidelines and an integral part of treatment, Dr. Frank said. Families "are your eyes and ears." They can provide important collateral information and help assess risk, and family involvement may lower litigation risk. Family conflict, however, has been linked to inpatient suicide (J. Nerv. Ment. Dis. 2010;198:315-28).

The patient’s "community" is now also part of every treatment plan at Dr. Frank’s institution. "No clinician can be everything at all moments to the patient. So how do we involve community?" she said. Community support might include the National Alliance on Mental Illness, Alcoholics Anonymous, Narcotics Anonymous, and bereavement support groups, for example. Dr. Frank also suggests removing weapons from the patient’s home.

Dr. Frank disclosed no relevant conflicts of interest.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster at the meeting.

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be about $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in a separate poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid. “What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year,” Marc Botteman of Pharmerit North America, said in an interview.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster at the meeting.

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be about $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in a separate poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid. “What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year,” Marc Botteman of Pharmerit North America, said in an interview.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster at the meeting.

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be about $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in a separate poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid. “What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year,” Marc Botteman of Pharmerit North America, said in an interview.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership.

Major Finding: Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and by 3.5 (about 29%) in the placebo arm, a nonsignificant difference.

Data Source: A trial of 178 postmenopausal women randomized to flaxseed bars or placebo bars for 6 weeks.

Disclosures: This study was funded by the National Cancer Institute. Dr. Pruthi reported having nothing to disclose.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

“Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars,” said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the meeting.

“Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed,” Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (33%) in the flaxseed arm, and 3.5 (29%) in the placebo arm (P = .29). “There was no significant difference in the reduction of hot flash scores between the two arms,” said Dr. Pruthi.

No statistically significant toxicity differences were experienced between study arms, but both groups reported substantial abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. “However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies,” she said.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes.

Source DR. PRUTHI

Major Finding: Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and by 3.5 (about 29%) in the placebo arm, a nonsignificant difference.

Data Source: A trial of 178 postmenopausal women randomized to flaxseed bars or placebo bars for 6 weeks.

Disclosures: This study was funded by the National Cancer Institute. Dr. Pruthi reported having nothing to disclose.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

“Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars,” said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the meeting.

“Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed,” Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (33%) in the flaxseed arm, and 3.5 (29%) in the placebo arm (P = .29). “There was no significant difference in the reduction of hot flash scores between the two arms,” said Dr. Pruthi.

No statistically significant toxicity differences were experienced between study arms, but both groups reported substantial abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. “However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies,” she said.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes.

Source DR. PRUTHI

Major Finding: Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and by 3.5 (about 29%) in the placebo arm, a nonsignificant difference.

Data Source: A trial of 178 postmenopausal women randomized to flaxseed bars or placebo bars for 6 weeks.

Disclosures: This study was funded by the National Cancer Institute. Dr. Pruthi reported having nothing to disclose.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

“Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars,” said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the meeting.

“Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed,” Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (33%) in the flaxseed arm, and 3.5 (29%) in the placebo arm (P = .29). “There was no significant difference in the reduction of hot flash scores between the two arms,” said Dr. Pruthi.

No statistically significant toxicity differences were experienced between study arms, but both groups reported substantial abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. “However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies,” she said.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes.

Source DR. PRUTHI

Major Finding: 25(OH)D concentration increments caused by supplementation prevented aromatase inhibitor–associated bone loss, independently of baseline 25(OH)D concentrations. Increasing levels of 25(OH)D at 3 months were inversely correlated to absolute bone loss (–0.004 g/cm

Data Source: Prospective cohort study of 156 postmenopausal nonosteoporotic women using adjuvant aromatase inhibitors in early breast cancer.

Disclosures: Dr. Sonia Servitja disclosed no relevant relationships. Chair and invited discussant Dr. Thomas J. Smith disclosed receiving research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – The bone loss associated with aromatase inhibitors was significantly slowed with increasing supplements of vitamin D in a prospective cohort study of 156 postmenopausal women.

“The bone loss was less, the higher your vitamin D level was maintained,” said session chair Dr. Thomas J. Smith of Massey Cancer Center of Virginia Commonwealth University. “This is one of the first intervention studies,” he said. “And the results are pretty striking.”

Dr. Sonia Servitja of Hospital del Mar in Barcelona, and colleagues, assessed the association between 25-hydroxy-vitamin D [25(OH)D] concentrations and bone loss at baseline, after 3 months of supplementation, and after 1 year, in patients receiving aromatase inhibitor therapy for early-stage breast cancer.

The 156 women in the prospective cohort had hormone-positive breast cancer and had initiated aromatase inhibitors during January 2006–June 2009.

All patients received daily oral calcium (1 g) and vitamin D₃ (800 IU). Patients with a baseline level of 25(OH)D less than 30 ng/mL received additional oral vitamin D₃. The women were a mean age of 62 years with a mean age of menopause onset of 50 years.

The magnitude of the bone-loss prevention correlated with incremental increases in 25(OH)D concentrations.

Each 10-ng/mL increase in 25(OH)D concentration at 3 months appeared to be associated with a 0.55% decrease in bone loss, which was almost a third of the average bone loss experienced by these patients, according to the study findings, presented as a poster at the meeting.

The findings suggest that vitamin D supplementation at doses higher than the standard of 400 to 800 IU/day might be useful to minimize bone loss in women starting out on aromatase inhibitors and who are not eligible for bisphosphonate therapy according to current guidelines.

Patients who achieved 25(OH)D concentrations of at leaset 40 ng/mL at 3 months experienced significantly reduced bone loss. In addition, 25(OH)D increases at 3 months were protective for relative bone loss.

Major Finding: 25(OH)D concentration increments caused by supplementation prevented aromatase inhibitor–associated bone loss, independently of baseline 25(OH)D concentrations. Increasing levels of 25(OH)D at 3 months were inversely correlated to absolute bone loss (–0.004 g/cm

Data Source: Prospective cohort study of 156 postmenopausal nonosteoporotic women using adjuvant aromatase inhibitors in early breast cancer.

Disclosures: Dr. Sonia Servitja disclosed no relevant relationships. Chair and invited discussant Dr. Thomas J. Smith disclosed receiving research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – The bone loss associated with aromatase inhibitors was significantly slowed with increasing supplements of vitamin D in a prospective cohort study of 156 postmenopausal women.

“The bone loss was less, the higher your vitamin D level was maintained,” said session chair Dr. Thomas J. Smith of Massey Cancer Center of Virginia Commonwealth University. “This is one of the first intervention studies,” he said. “And the results are pretty striking.”

Dr. Sonia Servitja of Hospital del Mar in Barcelona, and colleagues, assessed the association between 25-hydroxy-vitamin D [25(OH)D] concentrations and bone loss at baseline, after 3 months of supplementation, and after 1 year, in patients receiving aromatase inhibitor therapy for early-stage breast cancer.

The 156 women in the prospective cohort had hormone-positive breast cancer and had initiated aromatase inhibitors during January 2006–June 2009.

All patients received daily oral calcium (1 g) and vitamin D₃ (800 IU). Patients with a baseline level of 25(OH)D less than 30 ng/mL received additional oral vitamin D₃. The women were a mean age of 62 years with a mean age of menopause onset of 50 years.

The magnitude of the bone-loss prevention correlated with incremental increases in 25(OH)D concentrations.

Each 10-ng/mL increase in 25(OH)D concentration at 3 months appeared to be associated with a 0.55% decrease in bone loss, which was almost a third of the average bone loss experienced by these patients, according to the study findings, presented as a poster at the meeting.

The findings suggest that vitamin D supplementation at doses higher than the standard of 400 to 800 IU/day might be useful to minimize bone loss in women starting out on aromatase inhibitors and who are not eligible for bisphosphonate therapy according to current guidelines.

Patients who achieved 25(OH)D concentrations of at leaset 40 ng/mL at 3 months experienced significantly reduced bone loss. In addition, 25(OH)D increases at 3 months were protective for relative bone loss.

Major Finding: 25(OH)D concentration increments caused by supplementation prevented aromatase inhibitor–associated bone loss, independently of baseline 25(OH)D concentrations. Increasing levels of 25(OH)D at 3 months were inversely correlated to absolute bone loss (–0.004 g/cm

Data Source: Prospective cohort study of 156 postmenopausal nonosteoporotic women using adjuvant aromatase inhibitors in early breast cancer.

Disclosures: Dr. Sonia Servitja disclosed no relevant relationships. Chair and invited discussant Dr. Thomas J. Smith disclosed receiving research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – The bone loss associated with aromatase inhibitors was significantly slowed with increasing supplements of vitamin D in a prospective cohort study of 156 postmenopausal women.

“The bone loss was less, the higher your vitamin D level was maintained,” said session chair Dr. Thomas J. Smith of Massey Cancer Center of Virginia Commonwealth University. “This is one of the first intervention studies,” he said. “And the results are pretty striking.”

Dr. Sonia Servitja of Hospital del Mar in Barcelona, and colleagues, assessed the association between 25-hydroxy-vitamin D [25(OH)D] concentrations and bone loss at baseline, after 3 months of supplementation, and after 1 year, in patients receiving aromatase inhibitor therapy for early-stage breast cancer.

The 156 women in the prospective cohort had hormone-positive breast cancer and had initiated aromatase inhibitors during January 2006–June 2009.

All patients received daily oral calcium (1 g) and vitamin D₃ (800 IU). Patients with a baseline level of 25(OH)D less than 30 ng/mL received additional oral vitamin D₃. The women were a mean age of 62 years with a mean age of menopause onset of 50 years.

The magnitude of the bone-loss prevention correlated with incremental increases in 25(OH)D concentrations.

Each 10-ng/mL increase in 25(OH)D concentration at 3 months appeared to be associated with a 0.55% decrease in bone loss, which was almost a third of the average bone loss experienced by these patients, according to the study findings, presented as a poster at the meeting.

The findings suggest that vitamin D supplementation at doses higher than the standard of 400 to 800 IU/day might be useful to minimize bone loss in women starting out on aromatase inhibitors and who are not eligible for bisphosphonate therapy according to current guidelines.

Patients who achieved 25(OH)D concentrations of at leaset 40 ng/mL at 3 months experienced significantly reduced bone loss. In addition, 25(OH)D increases at 3 months were protective for relative bone loss.