We appreciate Dr. Nasrallah referencing our work to assert that “most SGAs are similar to FGAs.” (Current Psychiatry, Comments & Controversies, October 2013, p. 39-40; http://bit.ly/177QOy6). What we actually found in our 2003¹ and 2011² meta-analyses was that “some antipsychotics are more efficacious than others,” and the first-generation antipsychotic vs second-generation antipsychotic distinction is not very useful clinically.³ These findings have repeatedly been replicated.³

John M. Davis, MD
Professor
Department of Psychiatry
University of Illinois at Chicago
Chicago, Illinois

Ira D. Glick, MD
Professor Emeritus of Psychiatry and Behavioral Sciences
Department of Psychiatry
Stanford University School of Medicine
Stanford, California

We appreciate Dr. Nasrallah referencing our work to assert that “most SGAs are similar to FGAs.” (Current Psychiatry, Comments & Controversies, October 2013, p. 39-40; http://bit.ly/177QOy6). What we actually found in our 2003¹ and 2011² meta-analyses was that “some antipsychotics are more efficacious than others,” and the first-generation antipsychotic vs second-generation antipsychotic distinction is not very useful clinically.³ These findings have repeatedly been replicated.³

John M. Davis, MD
Professor
Department of Psychiatry
University of Illinois at Chicago
Chicago, Illinois

Ira D. Glick, MD
Professor Emeritus of Psychiatry and Behavioral Sciences
Department of Psychiatry
Stanford University School of Medicine
Stanford, California

We appreciate Dr. Nasrallah referencing our work to assert that “most SGAs are similar to FGAs.” (Current Psychiatry, Comments & Controversies, October 2013, p. 39-40; http://bit.ly/177QOy6). What we actually found in our 2003¹ and 2011² meta-analyses was that “some antipsychotics are more efficacious than others,” and the first-generation antipsychotic vs second-generation antipsychotic distinction is not very useful clinically.³ These findings have repeatedly been replicated.³

John M. Davis, MD
Professor
Department of Psychiatry
University of Illinois at Chicago
Chicago, Illinois

Ira D. Glick, MD
Professor Emeritus of Psychiatry and Behavioral Sciences
Department of Psychiatry
Stanford University School of Medicine
Stanford, California

Vidyard Video

Access Dr. Burkman's Webcasts on contraception:

• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• United States Medical Eligibility Criteria for Contraceptive Use, 2016
• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use

Vidyard Video

Access Dr. Burkman's Webcasts on contraception:

• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• United States Medical Eligibility Criteria for Contraceptive Use, 2016
• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use

Vidyard Video

Access Dr. Burkman's Webcasts on contraception:

• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• United States Medical Eligibility Criteria for Contraceptive Use, 2016
• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use

Thinking of joining an online physician collaboration network but don't know where to start?

Here is a list of large physician online communities and listservs to help you connect, communicate, and network with your colleagues.

Sermo: This online community of physicians has over 200,000 members in 68 specialties. It is a place where physicians can securely post questions, insights, and observations for discussion.

Medscape Physician Connect: This is another online private community of physicians that has over 170,000 members.

Doximity: This online networking site is similar to LinkedIn, except that is is only for physicians. Users create a profile to connect with colleagues and to access the "nation’s most complete physician directory," according to their website.

DermRounds: This online networking site is the Facebook of dermatology. Users can pose questions, share videos and images, learn about upcoming CME conferences, and more.

RxDerm-L: This listserv group is open to dermatologists and dermatology residents only. To subscribe, send an email to [email protected], and in the body of the message write "subscribe rxderm-L" followed by your name.

ACADERM-L: This listserv group is open to teaching dermatolgists, or dermatologists serving in an administraction for a dermatology program. To subscribe, send an email to [email protected], and in the body of the message write "subscribe acaderm-L" followed by your name.

AMA Listservs: The AMA offers multiple listservs, including ones for residents and fellows and young physicians.

Thinking of joining an online physician collaboration network but don't know where to start?

Here is a list of large physician online communities and listservs to help you connect, communicate, and network with your colleagues.

Sermo: This online community of physicians has over 200,000 members in 68 specialties. It is a place where physicians can securely post questions, insights, and observations for discussion.

Medscape Physician Connect: This is another online private community of physicians that has over 170,000 members.

Doximity: This online networking site is similar to LinkedIn, except that is is only for physicians. Users create a profile to connect with colleagues and to access the "nation’s most complete physician directory," according to their website.

DermRounds: This online networking site is the Facebook of dermatology. Users can pose questions, share videos and images, learn about upcoming CME conferences, and more.

RxDerm-L: This listserv group is open to dermatologists and dermatology residents only. To subscribe, send an email to [email protected], and in the body of the message write "subscribe rxderm-L" followed by your name.

ACADERM-L: This listserv group is open to teaching dermatolgists, or dermatologists serving in an administraction for a dermatology program. To subscribe, send an email to [email protected], and in the body of the message write "subscribe acaderm-L" followed by your name.

AMA Listservs: The AMA offers multiple listservs, including ones for residents and fellows and young physicians.

Thinking of joining an online physician collaboration network but don't know where to start?

Here is a list of large physician online communities and listservs to help you connect, communicate, and network with your colleagues.

Sermo: This online community of physicians has over 200,000 members in 68 specialties. It is a place where physicians can securely post questions, insights, and observations for discussion.

Medscape Physician Connect: This is another online private community of physicians that has over 170,000 members.

Doximity: This online networking site is similar to LinkedIn, except that is is only for physicians. Users create a profile to connect with colleagues and to access the "nation’s most complete physician directory," according to their website.

DermRounds: This online networking site is the Facebook of dermatology. Users can pose questions, share videos and images, learn about upcoming CME conferences, and more.

RxDerm-L: This listserv group is open to dermatologists and dermatology residents only. To subscribe, send an email to [email protected], and in the body of the message write "subscribe rxderm-L" followed by your name.

ACADERM-L: This listserv group is open to teaching dermatolgists, or dermatologists serving in an administraction for a dermatology program. To subscribe, send an email to [email protected], and in the body of the message write "subscribe acaderm-L" followed by your name.

AMA Listservs: The AMA offers multiple listservs, including ones for residents and fellows and young physicians.

According to a CDC study, 59% of physicians use social media networks. 

Do you use social media networking? If so, share your favorite places to network in the poll below, or leave a note for your colleagues in the comments field.

According to a CDC study, 59% of physicians use social media networks. 

Do you use social media networking? If so, share your favorite places to network in the poll below, or leave a note for your colleagues in the comments field.

According to a CDC study, 59% of physicians use social media networks. 

Do you use social media networking? If so, share your favorite places to network in the poll below, or leave a note for your colleagues in the comments field.

MIAMI – Patients with psoriatic arthritis had a higher prevalence and greater extent of coronary artery plaque in a pilot study comparison with healthy control patients that may point to increased risk independent of traditional cardiovascular risk factors.

In the study, coronary artery plaque as assessed by cardiac computed tomography angiography (CCTA) occurred in 39 (78%) of 50 patients with psoriatic arthritis, a significantly higher rate than that observed for healthy controls (11 of 25, 44%).

©vizualis/thinkstockphotos.com

Investigators not only measured plaque volume, but also assessed the type of plaque: calcified, noncalcified, or mixed. Mixed plaque predominated. This could be important because “noncalcified and mixed carry higher risk for rupture and later cardiovascular events,” Agnes Szentpetery, MD, a research fellow at St. Vincent’s University Hospital in Dublin, said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

She and her colleagues also found more clinically significant stenosis among the 50 participants with psoriatic arthritis, compared with 25 healthy controls matched for age, sex, smoking status, and presence of metabolic syndrome. “This pilot study is the first to assess coronary plaques in asymptomatic patients with psoriatic arthritis with CCTA,” Dr. Szentpetery said.

Total plaque volume was higher in the psoriatic arthritis group versus controls, and higher in the left main artery for psoriatic arthritis patients, both with and without metabolic syndrome.

The study points to increased risk independent of traditional cardiovascular risk factors. For example, CCTA revealed no difference in plaque volume between patients with and without metabolic disease. In addition, a previous study suggests “the burden of carotid artery plaques is higher in patients with psoriatic arthritis compared to those with psoriasis alone,” Dr. Szentpetery said, citing a cross-sectional study comparing 125 people with psoriasis to 114 others with psoriatic arthritis (Ann Rheum Dis. 2013 May;72[5]:715-20).

Perhaps not surprisingly, inflammation could be driving the association between psoriatic and cardiovascular disease risk. Other investigators suggest chronic, low-grade inflammation leads to atherosclerosis through a maladaptive immune response and altered lipid metabolism, for example (Nat Med. 2011 Nov;17[11]:1410-22).

In the current study, the patients with psoriatic arthritis had well-established disease, occurring for a mean duration of 19 years. Mean age was 58 years, and 54% were men. Approximately 60% were taking disease-modifying antirheumatic drugs, two-thirds were taking biologics, and about one-third were on combination treatment. Controls were similar demographically with a mean age of 57 years, and 52% were men.

Interestingly, Psoriasis Area and Severity Index (PASI) scores did not correlate with increased risk. During discussion after the presentation of the study, a researcher unaffiliated with the study offered an answer. “It could be their skin disease was controlled by the biologics. You had 67% on biologics,” said Nehal Mehta, MD, Clinical Research Scholar in the section of inflammation and cardiometabolic disease at the National Heart, Lung, and Blood Institute. “We at the NIH see a strong correlation between PASI and coronary artery disease risk.”

“We know methotrexate and anti-TNF agents can have a protective effect on atherosclerosis, but we did not look at this specifically,” Dr. Szentpetery said. Overall, PASI scores were relatively low in the study population, she added, which “may explain why we did not see the correlation with PASI scores.”

Dr. Szentpetery and Dr. Mehta had no relevant financial disclosures.

MIAMI – Patients with psoriatic arthritis had a higher prevalence and greater extent of coronary artery plaque in a pilot study comparison with healthy control patients that may point to increased risk independent of traditional cardiovascular risk factors.

In the study, coronary artery plaque as assessed by cardiac computed tomography angiography (CCTA) occurred in 39 (78%) of 50 patients with psoriatic arthritis, a significantly higher rate than that observed for healthy controls (11 of 25, 44%).

©vizualis/thinkstockphotos.com

Investigators not only measured plaque volume, but also assessed the type of plaque: calcified, noncalcified, or mixed. Mixed plaque predominated. This could be important because “noncalcified and mixed carry higher risk for rupture and later cardiovascular events,” Agnes Szentpetery, MD, a research fellow at St. Vincent’s University Hospital in Dublin, said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

She and her colleagues also found more clinically significant stenosis among the 50 participants with psoriatic arthritis, compared with 25 healthy controls matched for age, sex, smoking status, and presence of metabolic syndrome. “This pilot study is the first to assess coronary plaques in asymptomatic patients with psoriatic arthritis with CCTA,” Dr. Szentpetery said.

Total plaque volume was higher in the psoriatic arthritis group versus controls, and higher in the left main artery for psoriatic arthritis patients, both with and without metabolic syndrome.

The study points to increased risk independent of traditional cardiovascular risk factors. For example, CCTA revealed no difference in plaque volume between patients with and without metabolic disease. In addition, a previous study suggests “the burden of carotid artery plaques is higher in patients with psoriatic arthritis compared to those with psoriasis alone,” Dr. Szentpetery said, citing a cross-sectional study comparing 125 people with psoriasis to 114 others with psoriatic arthritis (Ann Rheum Dis. 2013 May;72[5]:715-20).

Perhaps not surprisingly, inflammation could be driving the association between psoriatic and cardiovascular disease risk. Other investigators suggest chronic, low-grade inflammation leads to atherosclerosis through a maladaptive immune response and altered lipid metabolism, for example (Nat Med. 2011 Nov;17[11]:1410-22).

In the current study, the patients with psoriatic arthritis had well-established disease, occurring for a mean duration of 19 years. Mean age was 58 years, and 54% were men. Approximately 60% were taking disease-modifying antirheumatic drugs, two-thirds were taking biologics, and about one-third were on combination treatment. Controls were similar demographically with a mean age of 57 years, and 52% were men.

Interestingly, Psoriasis Area and Severity Index (PASI) scores did not correlate with increased risk. During discussion after the presentation of the study, a researcher unaffiliated with the study offered an answer. “It could be their skin disease was controlled by the biologics. You had 67% on biologics,” said Nehal Mehta, MD, Clinical Research Scholar in the section of inflammation and cardiometabolic disease at the National Heart, Lung, and Blood Institute. “We at the NIH see a strong correlation between PASI and coronary artery disease risk.”

“We know methotrexate and anti-TNF agents can have a protective effect on atherosclerosis, but we did not look at this specifically,” Dr. Szentpetery said. Overall, PASI scores were relatively low in the study population, she added, which “may explain why we did not see the correlation with PASI scores.”

Dr. Szentpetery and Dr. Mehta had no relevant financial disclosures.

MIAMI – Patients with psoriatic arthritis had a higher prevalence and greater extent of coronary artery plaque in a pilot study comparison with healthy control patients that may point to increased risk independent of traditional cardiovascular risk factors.

In the study, coronary artery plaque as assessed by cardiac computed tomography angiography (CCTA) occurred in 39 (78%) of 50 patients with psoriatic arthritis, a significantly higher rate than that observed for healthy controls (11 of 25, 44%).

©vizualis/thinkstockphotos.com

Investigators not only measured plaque volume, but also assessed the type of plaque: calcified, noncalcified, or mixed. Mixed plaque predominated. This could be important because “noncalcified and mixed carry higher risk for rupture and later cardiovascular events,” Agnes Szentpetery, MD, a research fellow at St. Vincent’s University Hospital in Dublin, said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

She and her colleagues also found more clinically significant stenosis among the 50 participants with psoriatic arthritis, compared with 25 healthy controls matched for age, sex, smoking status, and presence of metabolic syndrome. “This pilot study is the first to assess coronary plaques in asymptomatic patients with psoriatic arthritis with CCTA,” Dr. Szentpetery said.

Total plaque volume was higher in the psoriatic arthritis group versus controls, and higher in the left main artery for psoriatic arthritis patients, both with and without metabolic syndrome.

The study points to increased risk independent of traditional cardiovascular risk factors. For example, CCTA revealed no difference in plaque volume between patients with and without metabolic disease. In addition, a previous study suggests “the burden of carotid artery plaques is higher in patients with psoriatic arthritis compared to those with psoriasis alone,” Dr. Szentpetery said, citing a cross-sectional study comparing 125 people with psoriasis to 114 others with psoriatic arthritis (Ann Rheum Dis. 2013 May;72[5]:715-20).

Perhaps not surprisingly, inflammation could be driving the association between psoriatic and cardiovascular disease risk. Other investigators suggest chronic, low-grade inflammation leads to atherosclerosis through a maladaptive immune response and altered lipid metabolism, for example (Nat Med. 2011 Nov;17[11]:1410-22).

In the current study, the patients with psoriatic arthritis had well-established disease, occurring for a mean duration of 19 years. Mean age was 58 years, and 54% were men. Approximately 60% were taking disease-modifying antirheumatic drugs, two-thirds were taking biologics, and about one-third were on combination treatment. Controls were similar demographically with a mean age of 57 years, and 52% were men.

Interestingly, Psoriasis Area and Severity Index (PASI) scores did not correlate with increased risk. During discussion after the presentation of the study, a researcher unaffiliated with the study offered an answer. “It could be their skin disease was controlled by the biologics. You had 67% on biologics,” said Nehal Mehta, MD, Clinical Research Scholar in the section of inflammation and cardiometabolic disease at the National Heart, Lung, and Blood Institute. “We at the NIH see a strong correlation between PASI and coronary artery disease risk.”

“We know methotrexate and anti-TNF agents can have a protective effect on atherosclerosis, but we did not look at this specifically,” Dr. Szentpetery said. Overall, PASI scores were relatively low in the study population, she added, which “may explain why we did not see the correlation with PASI scores.”

Dr. Szentpetery and Dr. Mehta had no relevant financial disclosures.

Micrograph showing LSCs

Image by Robert Paulson

New research suggests leukemia stem cells (LSCs) can “hide” in gonadal adipose tissue (GAT) and transform the tissue so they can survive treatment.

Experiments in a mouse model of chronic myeloid leukemia (CML) showed that LSCs are enriched in GAT.

While there, the LSCs create a microenvironment that supports leukemic growth and resistance to treatment, and expression of the fatty acid transporter CD36 makes LSCs particularly resistant.

Craig Jordan, PhD, of University of Colorado in Aurora, and his colleagues conducted this research and detailed their findings in Cell Stem Cell.

The researchers began by examining cancer cells found in GAT from mice with blast crisis CML. Rather than containing the expected mix of regular leukemia cells and LSCs, the tissue was enriched for LSCs.

And these GAT-resident LSCs used a different energy source than LSCs in the bone marrow microenvironment. The GAT-resident LSCs powered their survival and growth with fatty acids, manufacturing energy by the process of fatty acid oxidization.

In fact, the GAT-resident LSCs actively signaled fat to undergo lipolysis, which released fatty acids into the microenvironment.

“The basic biology was fascinating,” Dr Jordan said. “The tumor adapted the local environment to suit itself.”

Dr Jordan and his colleagues also found that CD36 played a role. CD36+ LSCs were enriched in GAT, were more likely to migrate to GAT than to bone marrow, and were protected from treatment by GAT.

The researchers tested the effects of several drugs (cytarabine, doxorubicin, etoposide, SN-38, irinotecan, and dasatinib) on CD36+ LSCs, CD36- LSCs, and bulk leukemia cells ex vivo.

Both CD36+ and CD36- LSCs were more resistant to treatment than bulk leukemia cells, but CD36+ LSCs were preferentially drug-resistant.

The researchers observed similar results in leukemic mice and found evidence to suggest that CD36 plays a similar role in patients with blast crisis CML and those with acute myeloid leukemia.

Micrograph showing LSCs

Image by Robert Paulson

New research suggests leukemia stem cells (LSCs) can “hide” in gonadal adipose tissue (GAT) and transform the tissue so they can survive treatment.

Experiments in a mouse model of chronic myeloid leukemia (CML) showed that LSCs are enriched in GAT.

While there, the LSCs create a microenvironment that supports leukemic growth and resistance to treatment, and expression of the fatty acid transporter CD36 makes LSCs particularly resistant.

Craig Jordan, PhD, of University of Colorado in Aurora, and his colleagues conducted this research and detailed their findings in Cell Stem Cell.

The researchers began by examining cancer cells found in GAT from mice with blast crisis CML. Rather than containing the expected mix of regular leukemia cells and LSCs, the tissue was enriched for LSCs.

And these GAT-resident LSCs used a different energy source than LSCs in the bone marrow microenvironment. The GAT-resident LSCs powered their survival and growth with fatty acids, manufacturing energy by the process of fatty acid oxidization.

In fact, the GAT-resident LSCs actively signaled fat to undergo lipolysis, which released fatty acids into the microenvironment.

“The basic biology was fascinating,” Dr Jordan said. “The tumor adapted the local environment to suit itself.”

Dr Jordan and his colleagues also found that CD36 played a role. CD36+ LSCs were enriched in GAT, were more likely to migrate to GAT than to bone marrow, and were protected from treatment by GAT.

The researchers tested the effects of several drugs (cytarabine, doxorubicin, etoposide, SN-38, irinotecan, and dasatinib) on CD36+ LSCs, CD36- LSCs, and bulk leukemia cells ex vivo.

Both CD36+ and CD36- LSCs were more resistant to treatment than bulk leukemia cells, but CD36+ LSCs were preferentially drug-resistant.

The researchers observed similar results in leukemic mice and found evidence to suggest that CD36 plays a similar role in patients with blast crisis CML and those with acute myeloid leukemia.

Micrograph showing LSCs

Image by Robert Paulson

New research suggests leukemia stem cells (LSCs) can “hide” in gonadal adipose tissue (GAT) and transform the tissue so they can survive treatment.

Experiments in a mouse model of chronic myeloid leukemia (CML) showed that LSCs are enriched in GAT.

While there, the LSCs create a microenvironment that supports leukemic growth and resistance to treatment, and expression of the fatty acid transporter CD36 makes LSCs particularly resistant.

Craig Jordan, PhD, of University of Colorado in Aurora, and his colleagues conducted this research and detailed their findings in Cell Stem Cell.

The researchers began by examining cancer cells found in GAT from mice with blast crisis CML. Rather than containing the expected mix of regular leukemia cells and LSCs, the tissue was enriched for LSCs.

And these GAT-resident LSCs used a different energy source than LSCs in the bone marrow microenvironment. The GAT-resident LSCs powered their survival and growth with fatty acids, manufacturing energy by the process of fatty acid oxidization.

In fact, the GAT-resident LSCs actively signaled fat to undergo lipolysis, which released fatty acids into the microenvironment.

“The basic biology was fascinating,” Dr Jordan said. “The tumor adapted the local environment to suit itself.”

Dr Jordan and his colleagues also found that CD36 played a role. CD36+ LSCs were enriched in GAT, were more likely to migrate to GAT than to bone marrow, and were protected from treatment by GAT.

The researchers tested the effects of several drugs (cytarabine, doxorubicin, etoposide, SN-38, irinotecan, and dasatinib) on CD36+ LSCs, CD36- LSCs, and bulk leukemia cells ex vivo.

Both CD36+ and CD36- LSCs were more resistant to treatment than bulk leukemia cells, but CD36+ LSCs were preferentially drug-resistant.

The researchers observed similar results in leukemic mice and found evidence to suggest that CD36 plays a similar role in patients with blast crisis CML and those with acute myeloid leukemia.

Ibrutinib (Imbruvica)

Photo courtesy of Janssen

Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).

This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial

(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and

simultaneously published in NEJM.

RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.

Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.

Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.

Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.

Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).

Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five

patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.

The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.

The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).

Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).

Ibrutinib (Imbruvica)

Photo courtesy of Janssen

Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).

This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial

(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and

simultaneously published in NEJM.

RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.

Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.

Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.

Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.

Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).

Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five

patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.

The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.

The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).

Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).

Ibrutinib (Imbruvica)

Photo courtesy of Janssen

Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).

This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial

(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and

simultaneously published in NEJM.

RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.

Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.

Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.

Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.

Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).

Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five

patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.

The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.

The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).

Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).

Preparing for radiation

Photo by Rhoda Baer

Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.

However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.

Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.

The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.

However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.

To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.

The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.

“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.

Results in males

The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).

In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.

They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).

They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).

And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).

The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).

The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.

“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”

Results in females

The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.

The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.

However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).

Preparing for radiation

Photo by Rhoda Baer

Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.

However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.

Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.

The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.

However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.

To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.

The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.

“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.

Results in males

The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).

In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.

They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).

They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).

And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).

The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).

The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.

“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”

Results in females

The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.

The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.

However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).

Preparing for radiation

Photo by Rhoda Baer

Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.

However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.

Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.

The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.

However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.

To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.

The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.

“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.

Results in males

The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).

In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.

They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).

They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).

And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).

The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).

The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.

“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”

Results in females

The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.

The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.

However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).

Chemotherapy drugs

Photo by Bill Branson

Results of a phase 3 study suggest the antipsychotic agent olanzapine can also be used to reduce nausea and vomiting caused by chemotherapy.

In this study, cancer patients receiving highly emetogenic chemotherapy also received combination anti-emetic therapy including olanzapine or placebo.

Those patients who received olanzapine were significantly less likely to experience nausea and vomiting in the 120 hours after starting chemotherapy.

These results were published in NEJM.

“We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,” said study author Steven Powell, MD, of Sanford Cancer Center in Sioux Falls, South Dakota.

“The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.”

Dr Powell and his colleagues evaluated cancer patients who had received no previous chemotherapy but were receiving cisplatin or cyclophosphamide and doxorubicin during the study period.

To prevent nausea and vomiting, all of the patients received a 5-HT3–receptor antagonist, dexamethasone, and an NK1-receptor antagonist. Roughly half also received olanzapine, and the other half received placebo.

Overall, 380 patients were evaluable—192 assigned to olanzapine and 188 to placebo.

In the first 24 hours after starting chemotherapy, the proportion of patients who did not have chemotherapy-induced nausea was significantly greater in the olanzapine arm than the placebo arm—74% and 45%, respectively (P=0.002).

The same was true at 25 hours to 120 hours after the start of chemotherapy—42% and 25%, respectively (P=0.002)—and for the overall 120-hour period—37% and 22%, respectively (P=0.002).

The complete response rate—defined as no vomiting and no rescue therapy—was significantly higher in the olanzapine arm than the placebo arm in the first 24 hours—86% and 65% (P<0.001)—at 25 hours to 120 hours—67% and 52%, respectively (P=0.007)—and overall—64% and 41%, respectively (P<0.001).

There were two grade 3 adverse events and three grade 4 adverse events in the olanzapine arm, but none of these were attributed to olanzapine.

Patients in the olanzapine arm had significantly increased sedation on day 2 compared with baseline, but this resolved on days 3, 4, and 5, although the patients were still receiving olanzapine on days 3 and 4.

Chemotherapy drugs

Photo by Bill Branson

Results of a phase 3 study suggest the antipsychotic agent olanzapine can also be used to reduce nausea and vomiting caused by chemotherapy.

In this study, cancer patients receiving highly emetogenic chemotherapy also received combination anti-emetic therapy including olanzapine or placebo.

Those patients who received olanzapine were significantly less likely to experience nausea and vomiting in the 120 hours after starting chemotherapy.

These results were published in NEJM.

“We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,” said study author Steven Powell, MD, of Sanford Cancer Center in Sioux Falls, South Dakota.

“The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.”

Dr Powell and his colleagues evaluated cancer patients who had received no previous chemotherapy but were receiving cisplatin or cyclophosphamide and doxorubicin during the study period.

To prevent nausea and vomiting, all of the patients received a 5-HT3–receptor antagonist, dexamethasone, and an NK1-receptor antagonist. Roughly half also received olanzapine, and the other half received placebo.

Overall, 380 patients were evaluable—192 assigned to olanzapine and 188 to placebo.

In the first 24 hours after starting chemotherapy, the proportion of patients who did not have chemotherapy-induced nausea was significantly greater in the olanzapine arm than the placebo arm—74% and 45%, respectively (P=0.002).

The same was true at 25 hours to 120 hours after the start of chemotherapy—42% and 25%, respectively (P=0.002)—and for the overall 120-hour period—37% and 22%, respectively (P=0.002).

The complete response rate—defined as no vomiting and no rescue therapy—was significantly higher in the olanzapine arm than the placebo arm in the first 24 hours—86% and 65% (P<0.001)—at 25 hours to 120 hours—67% and 52%, respectively (P=0.007)—and overall—64% and 41%, respectively (P<0.001).

There were two grade 3 adverse events and three grade 4 adverse events in the olanzapine arm, but none of these were attributed to olanzapine.

Patients in the olanzapine arm had significantly increased sedation on day 2 compared with baseline, but this resolved on days 3, 4, and 5, although the patients were still receiving olanzapine on days 3 and 4.

Chemotherapy drugs

Photo by Bill Branson

Results of a phase 3 study suggest the antipsychotic agent olanzapine can also be used to reduce nausea and vomiting caused by chemotherapy.

In this study, cancer patients receiving highly emetogenic chemotherapy also received combination anti-emetic therapy including olanzapine or placebo.

Those patients who received olanzapine were significantly less likely to experience nausea and vomiting in the 120 hours after starting chemotherapy.

These results were published in NEJM.

“We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,” said study author Steven Powell, MD, of Sanford Cancer Center in Sioux Falls, South Dakota.

“The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.”

Dr Powell and his colleagues evaluated cancer patients who had received no previous chemotherapy but were receiving cisplatin or cyclophosphamide and doxorubicin during the study period.

To prevent nausea and vomiting, all of the patients received a 5-HT3–receptor antagonist, dexamethasone, and an NK1-receptor antagonist. Roughly half also received olanzapine, and the other half received placebo.

Overall, 380 patients were evaluable—192 assigned to olanzapine and 188 to placebo.

In the first 24 hours after starting chemotherapy, the proportion of patients who did not have chemotherapy-induced nausea was significantly greater in the olanzapine arm than the placebo arm—74% and 45%, respectively (P=0.002).

The same was true at 25 hours to 120 hours after the start of chemotherapy—42% and 25%, respectively (P=0.002)—and for the overall 120-hour period—37% and 22%, respectively (P=0.002).

The complete response rate—defined as no vomiting and no rescue therapy—was significantly higher in the olanzapine arm than the placebo arm in the first 24 hours—86% and 65% (P<0.001)—at 25 hours to 120 hours—67% and 52%, respectively (P=0.007)—and overall—64% and 41%, respectively (P<0.001).

There were two grade 3 adverse events and three grade 4 adverse events in the olanzapine arm, but none of these were attributed to olanzapine.

Patients in the olanzapine arm had significantly increased sedation on day 2 compared with baseline, but this resolved on days 3, 4, and 5, although the patients were still receiving olanzapine on days 3 and 4.