HyQvia

Credit: Baxter

The US Food and Drug Administration (FDA) has approved a subcutaneous immune globulin product for use in adults with primary immunodeficiency (PI).

The product, HyQvia, is an immune globulin with a recombinant human hyaluronidase. It requires a single infusion every 3 to 4 weeks and 1 injection site per infusion to deliver a full therapeutic dose of immune globulin.

Current therapies require weekly or bi-weekly treatment with multiple infusion sites per treatment.

Baxter International Inc. expects to launch HyQvia in the US in the coming weeks. The product has been FDA-approved with a black-box warning detailing the risk of thrombosis associated with immune globulin products.

The immune globulin component of HyQvia is a 10% solution prepared from large pools of human plasma consisting of at least 98% IgG. The recombinant human hyaluronidase increases the dispersion and absorption of the immune globulin.

In a phase 3 trial, HyQvia compared well with intravenous human immune globulin 10% (IVIG).

Researchers compared the treatments at different time periods in a cohort of PI patients with a median age of 35 (range, 4-78 years). All 87 patients studied received IVIG, and 83 of the patients received at least 1 dose of HyQvia.

Patients received HyQvia for a median of 366 days and IVIG for a median of 91 days. The median ratio (HyQvia:IVIG) for the IgG dosage administered was 1.088 (range, 0.986–1.382).

Trough IgG concentrations, the incidence of infection, and rates of adverse events were generally similar during the HyQvia treatment period and the IVIG treatment period.

For patients aged 12 years and older, the median IgG C_trough values with HyQvia were approximately the same as with IVIG. The median trough ratio (HyQvia:IVIG) was 0.985.

For patients younger than 12 (n=11), the median IgG C_trough values were 10.0 and 9.6 g/L after HyQvia and IVIG, respectively, with a median trough ratio of 1.038.

The overall infection rates were 2.97 per patient-year with HyQvia and 4.51 per patient-year with IVIG.

During the HyQvia treatment period, the rate of acute serious bacterial infection (SBI) was 0.025 per patient-year. The rate of acute SBIs occurring during IVIG treatment was not reported.

In patients age 18 and older (n=59), the rate of acute SBIs was 0.00 per patient-year, and the overall infection rate was 3.20 per patient-year.

For this same patient group, the local adverse reaction rate was 0.286 per infusion.

The rate of systemic adverse events temporally related to an infusion was 0.20 per infusion with HyQvia and 0.33 per infusion with IVIG. There were no serious adverse events reported in these patients with either treatment.

HyQvia was approved in Europe in 2013 for adults with PI syndromes and myeloma or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections.

For more details on HyQvia, see the prescribing information.

HyQvia

Credit: Baxter

The US Food and Drug Administration (FDA) has approved a subcutaneous immune globulin product for use in adults with primary immunodeficiency (PI).

The product, HyQvia, is an immune globulin with a recombinant human hyaluronidase. It requires a single infusion every 3 to 4 weeks and 1 injection site per infusion to deliver a full therapeutic dose of immune globulin.

Current therapies require weekly or bi-weekly treatment with multiple infusion sites per treatment.

Baxter International Inc. expects to launch HyQvia in the US in the coming weeks. The product has been FDA-approved with a black-box warning detailing the risk of thrombosis associated with immune globulin products.

The immune globulin component of HyQvia is a 10% solution prepared from large pools of human plasma consisting of at least 98% IgG. The recombinant human hyaluronidase increases the dispersion and absorption of the immune globulin.

In a phase 3 trial, HyQvia compared well with intravenous human immune globulin 10% (IVIG).

Researchers compared the treatments at different time periods in a cohort of PI patients with a median age of 35 (range, 4-78 years). All 87 patients studied received IVIG, and 83 of the patients received at least 1 dose of HyQvia.

Patients received HyQvia for a median of 366 days and IVIG for a median of 91 days. The median ratio (HyQvia:IVIG) for the IgG dosage administered was 1.088 (range, 0.986–1.382).

Trough IgG concentrations, the incidence of infection, and rates of adverse events were generally similar during the HyQvia treatment period and the IVIG treatment period.

For patients aged 12 years and older, the median IgG C_trough values with HyQvia were approximately the same as with IVIG. The median trough ratio (HyQvia:IVIG) was 0.985.

For patients younger than 12 (n=11), the median IgG C_trough values were 10.0 and 9.6 g/L after HyQvia and IVIG, respectively, with a median trough ratio of 1.038.

The overall infection rates were 2.97 per patient-year with HyQvia and 4.51 per patient-year with IVIG.

During the HyQvia treatment period, the rate of acute serious bacterial infection (SBI) was 0.025 per patient-year. The rate of acute SBIs occurring during IVIG treatment was not reported.

In patients age 18 and older (n=59), the rate of acute SBIs was 0.00 per patient-year, and the overall infection rate was 3.20 per patient-year.

For this same patient group, the local adverse reaction rate was 0.286 per infusion.

The rate of systemic adverse events temporally related to an infusion was 0.20 per infusion with HyQvia and 0.33 per infusion with IVIG. There were no serious adverse events reported in these patients with either treatment.

HyQvia was approved in Europe in 2013 for adults with PI syndromes and myeloma or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections.

For more details on HyQvia, see the prescribing information.

HyQvia

Credit: Baxter

The US Food and Drug Administration (FDA) has approved a subcutaneous immune globulin product for use in adults with primary immunodeficiency (PI).

The product, HyQvia, is an immune globulin with a recombinant human hyaluronidase. It requires a single infusion every 3 to 4 weeks and 1 injection site per infusion to deliver a full therapeutic dose of immune globulin.

Current therapies require weekly or bi-weekly treatment with multiple infusion sites per treatment.

Baxter International Inc. expects to launch HyQvia in the US in the coming weeks. The product has been FDA-approved with a black-box warning detailing the risk of thrombosis associated with immune globulin products.

The immune globulin component of HyQvia is a 10% solution prepared from large pools of human plasma consisting of at least 98% IgG. The recombinant human hyaluronidase increases the dispersion and absorption of the immune globulin.

In a phase 3 trial, HyQvia compared well with intravenous human immune globulin 10% (IVIG).

Researchers compared the treatments at different time periods in a cohort of PI patients with a median age of 35 (range, 4-78 years). All 87 patients studied received IVIG, and 83 of the patients received at least 1 dose of HyQvia.

Patients received HyQvia for a median of 366 days and IVIG for a median of 91 days. The median ratio (HyQvia:IVIG) for the IgG dosage administered was 1.088 (range, 0.986–1.382).

Trough IgG concentrations, the incidence of infection, and rates of adverse events were generally similar during the HyQvia treatment period and the IVIG treatment period.

For patients aged 12 years and older, the median IgG C_trough values with HyQvia were approximately the same as with IVIG. The median trough ratio (HyQvia:IVIG) was 0.985.

For patients younger than 12 (n=11), the median IgG C_trough values were 10.0 and 9.6 g/L after HyQvia and IVIG, respectively, with a median trough ratio of 1.038.

The overall infection rates were 2.97 per patient-year with HyQvia and 4.51 per patient-year with IVIG.

During the HyQvia treatment period, the rate of acute serious bacterial infection (SBI) was 0.025 per patient-year. The rate of acute SBIs occurring during IVIG treatment was not reported.

In patients age 18 and older (n=59), the rate of acute SBIs was 0.00 per patient-year, and the overall infection rate was 3.20 per patient-year.

For this same patient group, the local adverse reaction rate was 0.286 per infusion.

The rate of systemic adverse events temporally related to an infusion was 0.20 per infusion with HyQvia and 0.33 per infusion with IVIG. There were no serious adverse events reported in these patients with either treatment.

HyQvia was approved in Europe in 2013 for adults with PI syndromes and myeloma or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections.

For more details on HyQvia, see the prescribing information.

Mark Klein, MD, and his team of fellow researchers came to the 2014 AVAHO Meeting to present their poster presentation, Incorporation of Palliative Care with Chemotherapy and Radiation in Patients Treated for Head and Neck Cancer.

To hear Dr. Klein discuss his research, watch the video below.

Mark Klein, MD, and his team of fellow researchers came to the 2014 AVAHO Meeting to present their poster presentation, Incorporation of Palliative Care with Chemotherapy and Radiation in Patients Treated for Head and Neck Cancer.

To hear Dr. Klein discuss his research, watch the video below.

Mark Klein, MD, and his team of fellow researchers came to the 2014 AVAHO Meeting to present their poster presentation, Incorporation of Palliative Care with Chemotherapy and Radiation in Patients Treated for Head and Neck Cancer.

To hear Dr. Klein discuss his research, watch the video below.

Michael Kelley, MD, presented a session on how an improved understanding of lung cancer screening in the VA Health Care System can help physicians better identify the inherent biases associated with uncontrolled trials. According to Kelley—who works as the national program director of oncology for the Durham VAMC in North Carolina—patients with lung cancer can often face biases such as the healthy volunteer bias, the lead-time bias, and the overdiagnosis bias. These can often lead to a misidentification and failure to send the right candidates for screening.

Dr. Kelley’s presentation discussed a limited pilot study being conducted by the VA known as the National Lung Screening Trial. This aim of the trial is to collect data to help identify the right candidates for screening and to determine if additional tests, such as CT scans, can help identify barriers in lung cancer treatment. Dr. Kelley hopes that the inclusion of this data during lung cancer screening can reduce and eventually eliminate lung cancer-associated mortality in the VA.

Michael Kelley, MD, presented a session on how an improved understanding of lung cancer screening in the VA Health Care System can help physicians better identify the inherent biases associated with uncontrolled trials. According to Kelley—who works as the national program director of oncology for the Durham VAMC in North Carolina—patients with lung cancer can often face biases such as the healthy volunteer bias, the lead-time bias, and the overdiagnosis bias. These can often lead to a misidentification and failure to send the right candidates for screening.

Dr. Kelley’s presentation discussed a limited pilot study being conducted by the VA known as the National Lung Screening Trial. This aim of the trial is to collect data to help identify the right candidates for screening and to determine if additional tests, such as CT scans, can help identify barriers in lung cancer treatment. Dr. Kelley hopes that the inclusion of this data during lung cancer screening can reduce and eventually eliminate lung cancer-associated mortality in the VA.

Michael Kelley, MD, presented a session on how an improved understanding of lung cancer screening in the VA Health Care System can help physicians better identify the inherent biases associated with uncontrolled trials. According to Kelley—who works as the national program director of oncology for the Durham VAMC in North Carolina—patients with lung cancer can often face biases such as the healthy volunteer bias, the lead-time bias, and the overdiagnosis bias. These can often lead to a misidentification and failure to send the right candidates for screening.

Dr. Kelley’s presentation discussed a limited pilot study being conducted by the VA known as the National Lung Screening Trial. This aim of the trial is to collect data to help identify the right candidates for screening and to determine if additional tests, such as CT scans, can help identify barriers in lung cancer treatment. Dr. Kelley hopes that the inclusion of this data during lung cancer screening can reduce and eventually eliminate lung cancer-associated mortality in the VA.

Anemia testing device

Credit: Gary Meek

A simple device could provide more rapid diagnosis of anemia and allow for inexpensive at-home monitoring, according to a paper published in The Journal of Clinical Investigation.

The disposable device analyzes a single droplet of blood using a chemical reagent that produces visible color changes corresponding to different levels of anemia.

The test produces results in about 60 seconds, and a smartphone application can correlate the visual results to specific hemoglobin levels.

“Our goal is to get this device into patients’ hands so they can diagnose and monitor anemia themselves,” said Wilbur Lam, MD, PhD, of the Georgia Institute of Technology and Emory University in Atlanta.

“Patients could use this device in a way that’s very similar to how diabetics use glucose-monitoring devices, but this will be even simpler because this is a visual-based test that doesn’t require an additional electrical device to analyze the results.”

The device was developed through a collaboration between Emory University, Children’s Healthcare of Atlanta, and Georgia Tech. It grew out of a 2011 undergraduate senior design project in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Using a 2-piece prototype device, the test works this way: A patient sticks a finger with a lance to produce a droplet of blood. The device’s cap, a small vial, is touched to the droplet, drawing in a precise amount of blood using capillary action.

The cap containing the blood sample is then placed onto the body of the clear plastic test kit, which contains the chemical reagent. After the cap is closed, the device is briefly shaken to mix the blood and reagent.

“When the capillary is filled, we have a very precise volume of blood, about 5 microliters, which is less than a droplet—much less than what is required by other anemia tests,” explained Erika Tyburski, the paper’s first author and leader of the team that developed the device.

Hemoglobin then serves as a catalyst for a reduction-oxidation reaction that takes place in the device. After about 45 seconds, the reaction is complete, and the user sees a color ranging from green-blue to red, indicating the degree of anemia.

A label on the device helps with interpretation of the color, or patients could use a smartphone app that automatically correlates the color to a specific hemoglobin level.

To evaluate sensitivity and specificity of the device, Tyburski studied blood taken from 238 pediatric and adult patients. Each blood sample was tested 4 times using the device, and the results were compared to reports provided by conventional hematology analyzers.

The results of the 1-minute test were consistent with those of the conventional analyses. The smartphone app produced the best results for measuring severe anemia.

“The test doesn’t require a skilled technician or a draw of venous blood, and you see the results immediately,” Dr Lam said. “We think this is an empowering system, both for the general public and for our patients.”

Tyburski and Dr Lam have teamed up with 2 other partners to launch a startup company called Sanguina to commercialize the test, which will be known as AnemoCheck™.

The test will require approval from the US Food and Drug Administration, but the researchers believe the device could be on pharmacy shelves sometime in 2016.

The team also plans to study how the test may be applied to sickle cell anemia and other diseases.

Anemia testing device

Credit: Gary Meek

A simple device could provide more rapid diagnosis of anemia and allow for inexpensive at-home monitoring, according to a paper published in The Journal of Clinical Investigation.

The disposable device analyzes a single droplet of blood using a chemical reagent that produces visible color changes corresponding to different levels of anemia.

The test produces results in about 60 seconds, and a smartphone application can correlate the visual results to specific hemoglobin levels.

“Our goal is to get this device into patients’ hands so they can diagnose and monitor anemia themselves,” said Wilbur Lam, MD, PhD, of the Georgia Institute of Technology and Emory University in Atlanta.

“Patients could use this device in a way that’s very similar to how diabetics use glucose-monitoring devices, but this will be even simpler because this is a visual-based test that doesn’t require an additional electrical device to analyze the results.”

The device was developed through a collaboration between Emory University, Children’s Healthcare of Atlanta, and Georgia Tech. It grew out of a 2011 undergraduate senior design project in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Using a 2-piece prototype device, the test works this way: A patient sticks a finger with a lance to produce a droplet of blood. The device’s cap, a small vial, is touched to the droplet, drawing in a precise amount of blood using capillary action.

The cap containing the blood sample is then placed onto the body of the clear plastic test kit, which contains the chemical reagent. After the cap is closed, the device is briefly shaken to mix the blood and reagent.

“When the capillary is filled, we have a very precise volume of blood, about 5 microliters, which is less than a droplet—much less than what is required by other anemia tests,” explained Erika Tyburski, the paper’s first author and leader of the team that developed the device.

Hemoglobin then serves as a catalyst for a reduction-oxidation reaction that takes place in the device. After about 45 seconds, the reaction is complete, and the user sees a color ranging from green-blue to red, indicating the degree of anemia.

A label on the device helps with interpretation of the color, or patients could use a smartphone app that automatically correlates the color to a specific hemoglobin level.

To evaluate sensitivity and specificity of the device, Tyburski studied blood taken from 238 pediatric and adult patients. Each blood sample was tested 4 times using the device, and the results were compared to reports provided by conventional hematology analyzers.

The results of the 1-minute test were consistent with those of the conventional analyses. The smartphone app produced the best results for measuring severe anemia.

“The test doesn’t require a skilled technician or a draw of venous blood, and you see the results immediately,” Dr Lam said. “We think this is an empowering system, both for the general public and for our patients.”

Tyburski and Dr Lam have teamed up with 2 other partners to launch a startup company called Sanguina to commercialize the test, which will be known as AnemoCheck™.

The test will require approval from the US Food and Drug Administration, but the researchers believe the device could be on pharmacy shelves sometime in 2016.

The team also plans to study how the test may be applied to sickle cell anemia and other diseases.

Anemia testing device

Credit: Gary Meek

A simple device could provide more rapid diagnosis of anemia and allow for inexpensive at-home monitoring, according to a paper published in The Journal of Clinical Investigation.

The disposable device analyzes a single droplet of blood using a chemical reagent that produces visible color changes corresponding to different levels of anemia.

The test produces results in about 60 seconds, and a smartphone application can correlate the visual results to specific hemoglobin levels.

“Our goal is to get this device into patients’ hands so they can diagnose and monitor anemia themselves,” said Wilbur Lam, MD, PhD, of the Georgia Institute of Technology and Emory University in Atlanta.

“Patients could use this device in a way that’s very similar to how diabetics use glucose-monitoring devices, but this will be even simpler because this is a visual-based test that doesn’t require an additional electrical device to analyze the results.”

The device was developed through a collaboration between Emory University, Children’s Healthcare of Atlanta, and Georgia Tech. It grew out of a 2011 undergraduate senior design project in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Using a 2-piece prototype device, the test works this way: A patient sticks a finger with a lance to produce a droplet of blood. The device’s cap, a small vial, is touched to the droplet, drawing in a precise amount of blood using capillary action.

The cap containing the blood sample is then placed onto the body of the clear plastic test kit, which contains the chemical reagent. After the cap is closed, the device is briefly shaken to mix the blood and reagent.

“When the capillary is filled, we have a very precise volume of blood, about 5 microliters, which is less than a droplet—much less than what is required by other anemia tests,” explained Erika Tyburski, the paper’s first author and leader of the team that developed the device.

Hemoglobin then serves as a catalyst for a reduction-oxidation reaction that takes place in the device. After about 45 seconds, the reaction is complete, and the user sees a color ranging from green-blue to red, indicating the degree of anemia.

A label on the device helps with interpretation of the color, or patients could use a smartphone app that automatically correlates the color to a specific hemoglobin level.

To evaluate sensitivity and specificity of the device, Tyburski studied blood taken from 238 pediatric and adult patients. Each blood sample was tested 4 times using the device, and the results were compared to reports provided by conventional hematology analyzers.

The results of the 1-minute test were consistent with those of the conventional analyses. The smartphone app produced the best results for measuring severe anemia.

“The test doesn’t require a skilled technician or a draw of venous blood, and you see the results immediately,” Dr Lam said. “We think this is an empowering system, both for the general public and for our patients.”

Tyburski and Dr Lam have teamed up with 2 other partners to launch a startup company called Sanguina to commercialize the test, which will be known as AnemoCheck™.

The test will require approval from the US Food and Drug Administration, but the researchers believe the device could be on pharmacy shelves sometime in 2016.

The team also plans to study how the test may be applied to sickle cell anemia and other diseases.

Vial of heparin

Hospira Inc. has initiated a US-wide recall of 1 lot of heparin sodium, following a customer report of particulate in a single unit.

The recall affects lot 41-046-JT of 1000 USP Heparin Units/500 mL (2 USP Heparin Units/mL), in 0.9% Sodium Chloride Injection, 500 mL (NDC 0409-7620-03; expiration date November 1, 2015).

The foreign particle found in a unit from this lot was a human hair sealed between the tube and the film at the round seal of the unused administrative port on the non-print side of the container.

To date, Hospira has not received reports of any adverse events associated with this issue. The root cause has not been determined and is under investigation.

Heparin sodium injection is indicated as an anticoagulant to maintain catheter patency. In the event that a particulate breaks and pieces are able to pass through the intravenous catheter, injected particulate material may result in local inflammation, phlebitis, and/or low-level allergic response.

Capillaries may become occluded. Patients with a pre-existing condition of trauma or another medical condition that adversely affects the microvascular blood supply are at an increased risk.

The lot of heparin affected by this recall was distributed nationwide between June 2014 and August 2014 to wholesalers/distributors, hospitals, and pharmacies.

Anyone with existing inventory should stop use and distribution and quarantine the product immediately. Customers should also inform potential users of this product about the recall.

Hospira will be notifying its direct distributors/customers via a recall letter and will arrange for the impacted product to be returned to Stericycle. For additional assistance, call Stericycle at 1-855-201-4337 between the hours of 8 am and 5pm ET, Monday through Friday.

For clinical inquiries, contact Hospira. To report adverse events or product complaints, call 1-800-441-4100 (8 am to 5 pm CT, Monday through Friday) or email [email protected].

For medical inquiries, call 1-800-615-0187 (available 24 hours a day, 7 days per week) or email [email protected].

Adverse reactions or quality problems associated with this product can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vial of heparin

Hospira Inc. has initiated a US-wide recall of 1 lot of heparin sodium, following a customer report of particulate in a single unit.

The recall affects lot 41-046-JT of 1000 USP Heparin Units/500 mL (2 USP Heparin Units/mL), in 0.9% Sodium Chloride Injection, 500 mL (NDC 0409-7620-03; expiration date November 1, 2015).

The foreign particle found in a unit from this lot was a human hair sealed between the tube and the film at the round seal of the unused administrative port on the non-print side of the container.

To date, Hospira has not received reports of any adverse events associated with this issue. The root cause has not been determined and is under investigation.

Heparin sodium injection is indicated as an anticoagulant to maintain catheter patency. In the event that a particulate breaks and pieces are able to pass through the intravenous catheter, injected particulate material may result in local inflammation, phlebitis, and/or low-level allergic response.

Capillaries may become occluded. Patients with a pre-existing condition of trauma or another medical condition that adversely affects the microvascular blood supply are at an increased risk.

The lot of heparin affected by this recall was distributed nationwide between June 2014 and August 2014 to wholesalers/distributors, hospitals, and pharmacies.

Anyone with existing inventory should stop use and distribution and quarantine the product immediately. Customers should also inform potential users of this product about the recall.

Hospira will be notifying its direct distributors/customers via a recall letter and will arrange for the impacted product to be returned to Stericycle. For additional assistance, call Stericycle at 1-855-201-4337 between the hours of 8 am and 5pm ET, Monday through Friday.

For clinical inquiries, contact Hospira. To report adverse events or product complaints, call 1-800-441-4100 (8 am to 5 pm CT, Monday through Friday) or email [email protected].

For medical inquiries, call 1-800-615-0187 (available 24 hours a day, 7 days per week) or email [email protected].

Adverse reactions or quality problems associated with this product can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vial of heparin

Hospira Inc. has initiated a US-wide recall of 1 lot of heparin sodium, following a customer report of particulate in a single unit.

The recall affects lot 41-046-JT of 1000 USP Heparin Units/500 mL (2 USP Heparin Units/mL), in 0.9% Sodium Chloride Injection, 500 mL (NDC 0409-7620-03; expiration date November 1, 2015).

The foreign particle found in a unit from this lot was a human hair sealed between the tube and the film at the round seal of the unused administrative port on the non-print side of the container.

To date, Hospira has not received reports of any adverse events associated with this issue. The root cause has not been determined and is under investigation.

Heparin sodium injection is indicated as an anticoagulant to maintain catheter patency. In the event that a particulate breaks and pieces are able to pass through the intravenous catheter, injected particulate material may result in local inflammation, phlebitis, and/or low-level allergic response.

Capillaries may become occluded. Patients with a pre-existing condition of trauma or another medical condition that adversely affects the microvascular blood supply are at an increased risk.

The lot of heparin affected by this recall was distributed nationwide between June 2014 and August 2014 to wholesalers/distributors, hospitals, and pharmacies.

Anyone with existing inventory should stop use and distribution and quarantine the product immediately. Customers should also inform potential users of this product about the recall.

Hospira will be notifying its direct distributors/customers via a recall letter and will arrange for the impacted product to be returned to Stericycle. For additional assistance, call Stericycle at 1-855-201-4337 between the hours of 8 am and 5pm ET, Monday through Friday.

For clinical inquiries, contact Hospira. To report adverse events or product complaints, call 1-800-441-4100 (8 am to 5 pm CT, Monday through Friday) or email [email protected].

For medical inquiries, call 1-800-615-0187 (available 24 hours a day, 7 days per week) or email [email protected].

Adverse reactions or quality problems associated with this product can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Ever since the 2001 attack on the World Trade Center, I have associated a bright, sunny day with disaster. I vividly remember what a beautiful morning that was -- a crystal blue cloudless sky, low humidity, and a cool, comfortable temperature. Who could be unhappy on such a marvelous day?

On the other hand, my experience living in a northern climate taught me that winter was another story. Getting up in the dark to go to school or work was a miserable experience, followed by coming home in the dark and endless hours of biting cold and bitter nights. I was not surprised to learn later in my residency training about seasonal affective disorder and about the effects of light on mood. With this background, I felt primed to write a column about a new study, "Direct Effect of Sunshine on Suicide" (JAMA Psychiatry 2014 Sept. 10 [doi:10.1001/jamapsychiatry.2014.1198]).

In this study, investigators looked at public records of confirmed suicides in Austria between January 1970 and May 2010.They gathered 40 years of daily sunlight data from 86 meteorological stations. The amount of sunlight was defined as the duration of time that light intensity was higher than 120 watts per square meter, which apparently is the amount of light typically seen just after sunrise or just before sunset. Using this information, they compared daily suicide rates with the average daily duration of sunshine. Since sunlight varies in both duration and intensity over the seasons, the researchers used statistical methods to compensate for this, which distinguished this work from previous similar suicide studies. The authors then compared suicide rates by gender and method.

There were 69,462 suicide deaths, the majority through violent means such as hanging, drowning, shooting, or jumping. Only a quarter of the deaths were through nonviolent means such as poisoning. A significant correlation was found between the daily suicide rate and the daily duration of sunshine, but the surprising result was that sunshine appeared to have both a provocative and a palliative effect. Suicide rates climbed with increasing sunshine during the 10 days leading up to a suicide for suicides as a whole, for suicide through violent means, and for women. Sunlight had no effect on suicides for nonviolent deaths.

As a group, there was a negative correlation with deaths for the 14-60 days prior to a given suicide. Violent suicides were less likely during this time. The effects of sunshine also were specific to gender. There was a negative correlation, or apparently a protective effect, for men but not for women in the preceding 14-60 days.

Many physiologic reasons explain why light can affect mood, such as disruption of circadian rhythms and altered melatonin levels, or disturbances in serotonin or monoamine systems. There have also been social explanations for why suicides show seasonal variation. The "winter blues" have been explained by the stress of holiday preparation and its associated high expectations, family conflict, and increased alcohol use around this time. The authors concluded that one reason sunlight may increase suicide rates is that sunlight may improve motivation before lifting mood, giving a person the impetus to act on self-destructive impulses.

How this relates to the use of light boxes to treat seasonal affective disorder remains to be seen. Traditionally, this intervention is favored because of the relatively few associated hazards and side effects compared to pharmacotherapy. This risk-benefit ratio may need to be reassessed as more studies address the sunlight-suicide connection. Still, given that these devices are not Food and Drug Administration‑regulated or approved, I doubt we will be seeing the equivalent of a “black box” warning anytime in the near future.

Dr. Hanson is a forensic psychiatrist and coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work.” The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson's employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Ever since the 2001 attack on the World Trade Center, I have associated a bright, sunny day with disaster. I vividly remember what a beautiful morning that was -- a crystal blue cloudless sky, low humidity, and a cool, comfortable temperature. Who could be unhappy on such a marvelous day?

On the other hand, my experience living in a northern climate taught me that winter was another story. Getting up in the dark to go to school or work was a miserable experience, followed by coming home in the dark and endless hours of biting cold and bitter nights. I was not surprised to learn later in my residency training about seasonal affective disorder and about the effects of light on mood. With this background, I felt primed to write a column about a new study, "Direct Effect of Sunshine on Suicide" (JAMA Psychiatry 2014 Sept. 10 [doi:10.1001/jamapsychiatry.2014.1198]).

In this study, investigators looked at public records of confirmed suicides in Austria between January 1970 and May 2010.They gathered 40 years of daily sunlight data from 86 meteorological stations. The amount of sunlight was defined as the duration of time that light intensity was higher than 120 watts per square meter, which apparently is the amount of light typically seen just after sunrise or just before sunset. Using this information, they compared daily suicide rates with the average daily duration of sunshine. Since sunlight varies in both duration and intensity over the seasons, the researchers used statistical methods to compensate for this, which distinguished this work from previous similar suicide studies. The authors then compared suicide rates by gender and method.

There were 69,462 suicide deaths, the majority through violent means such as hanging, drowning, shooting, or jumping. Only a quarter of the deaths were through nonviolent means such as poisoning. A significant correlation was found between the daily suicide rate and the daily duration of sunshine, but the surprising result was that sunshine appeared to have both a provocative and a palliative effect. Suicide rates climbed with increasing sunshine during the 10 days leading up to a suicide for suicides as a whole, for suicide through violent means, and for women. Sunlight had no effect on suicides for nonviolent deaths.

As a group, there was a negative correlation with deaths for the 14-60 days prior to a given suicide. Violent suicides were less likely during this time. The effects of sunshine also were specific to gender. There was a negative correlation, or apparently a protective effect, for men but not for women in the preceding 14-60 days.

Many physiologic reasons explain why light can affect mood, such as disruption of circadian rhythms and altered melatonin levels, or disturbances in serotonin or monoamine systems. There have also been social explanations for why suicides show seasonal variation. The "winter blues" have been explained by the stress of holiday preparation and its associated high expectations, family conflict, and increased alcohol use around this time. The authors concluded that one reason sunlight may increase suicide rates is that sunlight may improve motivation before lifting mood, giving a person the impetus to act on self-destructive impulses.

How this relates to the use of light boxes to treat seasonal affective disorder remains to be seen. Traditionally, this intervention is favored because of the relatively few associated hazards and side effects compared to pharmacotherapy. This risk-benefit ratio may need to be reassessed as more studies address the sunlight-suicide connection. Still, given that these devices are not Food and Drug Administration‑regulated or approved, I doubt we will be seeing the equivalent of a “black box” warning anytime in the near future.

Dr. Hanson is a forensic psychiatrist and coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work.” The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson's employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Ever since the 2001 attack on the World Trade Center, I have associated a bright, sunny day with disaster. I vividly remember what a beautiful morning that was -- a crystal blue cloudless sky, low humidity, and a cool, comfortable temperature. Who could be unhappy on such a marvelous day?

On the other hand, my experience living in a northern climate taught me that winter was another story. Getting up in the dark to go to school or work was a miserable experience, followed by coming home in the dark and endless hours of biting cold and bitter nights. I was not surprised to learn later in my residency training about seasonal affective disorder and about the effects of light on mood. With this background, I felt primed to write a column about a new study, "Direct Effect of Sunshine on Suicide" (JAMA Psychiatry 2014 Sept. 10 [doi:10.1001/jamapsychiatry.2014.1198]).

In this study, investigators looked at public records of confirmed suicides in Austria between January 1970 and May 2010.They gathered 40 years of daily sunlight data from 86 meteorological stations. The amount of sunlight was defined as the duration of time that light intensity was higher than 120 watts per square meter, which apparently is the amount of light typically seen just after sunrise or just before sunset. Using this information, they compared daily suicide rates with the average daily duration of sunshine. Since sunlight varies in both duration and intensity over the seasons, the researchers used statistical methods to compensate for this, which distinguished this work from previous similar suicide studies. The authors then compared suicide rates by gender and method.

There were 69,462 suicide deaths, the majority through violent means such as hanging, drowning, shooting, or jumping. Only a quarter of the deaths were through nonviolent means such as poisoning. A significant correlation was found between the daily suicide rate and the daily duration of sunshine, but the surprising result was that sunshine appeared to have both a provocative and a palliative effect. Suicide rates climbed with increasing sunshine during the 10 days leading up to a suicide for suicides as a whole, for suicide through violent means, and for women. Sunlight had no effect on suicides for nonviolent deaths.

As a group, there was a negative correlation with deaths for the 14-60 days prior to a given suicide. Violent suicides were less likely during this time. The effects of sunshine also were specific to gender. There was a negative correlation, or apparently a protective effect, for men but not for women in the preceding 14-60 days.

Many physiologic reasons explain why light can affect mood, such as disruption of circadian rhythms and altered melatonin levels, or disturbances in serotonin or monoamine systems. There have also been social explanations for why suicides show seasonal variation. The "winter blues" have been explained by the stress of holiday preparation and its associated high expectations, family conflict, and increased alcohol use around this time. The authors concluded that one reason sunlight may increase suicide rates is that sunlight may improve motivation before lifting mood, giving a person the impetus to act on self-destructive impulses.

How this relates to the use of light boxes to treat seasonal affective disorder remains to be seen. Traditionally, this intervention is favored because of the relatively few associated hazards and side effects compared to pharmacotherapy. This risk-benefit ratio may need to be reassessed as more studies address the sunlight-suicide connection. Still, given that these devices are not Food and Drug Administration‑regulated or approved, I doubt we will be seeing the equivalent of a “black box” warning anytime in the near future.

Dr. Hanson is a forensic psychiatrist and coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work.” The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson's employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Plasmodium oocysts

(blue) in mosquito gut

Credit: Antoine Nicot

and Jacques Denoyelle

Experiments in canaries have shown that Plasmodium parasites react when non-infected mosquitoes bite their hosts, and the parasite responses increase transmission to the mosquito.

Like many other parasites, Plasmodium goes through a phase of chronic infection during which most of the parasites are in a dormant stage, and parasite numbers in the blood are very low.

Every now and then, however, the parasites “relapse,” and numbers increase, but the cause of this is not well understood.

So researchers set out to determine whether bites from non-infected mosquitoes can trigger relapses in Plasmodium during chronic infections, and whether relapses are associated with higher rates of transmission to the vector, ie, infection of the mosquitoes.

Sylvain Gandon, PhD, of the Université de Montpellier in France, and his colleagues described this research in PLOS Pathogens.

Specifically, the researchers studied the interaction between Plasmodium relictum, the parasite responsible for most cases of bird malaria in European songbirds, and its natural vector, a mosquito called Culex pipiens.

The team infected domestic canaries with P relictum and tested whether bites from uninfected Culex mosquitoes could trigger malaria relapses during chronic infection.

Indeed, parasite numbers in the blood routinely increased after the canaries were bitten. Moreover, the higher parasite loads following mosquito bites translated into higher infection rates in the mosquitoes.

The researchers therefore concluded that P relictum has the ability to boost its own transmission during the chronic phase of the vertebrate infection after being exposed to mosquito bites.

Although it is unclear if this also occurs in humans, the team suggested that better understanding of this phenomenon could eventually improve malaria control.

They also pointed out that many other pathogens alternate between acute and dormant phases. So better understanding of the ecological determinants and evolutionary forces governing parasite relapses could have wide-ranging applications.

Plasmodium oocysts

(blue) in mosquito gut

Credit: Antoine Nicot

and Jacques Denoyelle

Experiments in canaries have shown that Plasmodium parasites react when non-infected mosquitoes bite their hosts, and the parasite responses increase transmission to the mosquito.

Like many other parasites, Plasmodium goes through a phase of chronic infection during which most of the parasites are in a dormant stage, and parasite numbers in the blood are very low.

Every now and then, however, the parasites “relapse,” and numbers increase, but the cause of this is not well understood.

So researchers set out to determine whether bites from non-infected mosquitoes can trigger relapses in Plasmodium during chronic infections, and whether relapses are associated with higher rates of transmission to the vector, ie, infection of the mosquitoes.

Sylvain Gandon, PhD, of the Université de Montpellier in France, and his colleagues described this research in PLOS Pathogens.

Specifically, the researchers studied the interaction between Plasmodium relictum, the parasite responsible for most cases of bird malaria in European songbirds, and its natural vector, a mosquito called Culex pipiens.

The team infected domestic canaries with P relictum and tested whether bites from uninfected Culex mosquitoes could trigger malaria relapses during chronic infection.

Indeed, parasite numbers in the blood routinely increased after the canaries were bitten. Moreover, the higher parasite loads following mosquito bites translated into higher infection rates in the mosquitoes.

The researchers therefore concluded that P relictum has the ability to boost its own transmission during the chronic phase of the vertebrate infection after being exposed to mosquito bites.

Although it is unclear if this also occurs in humans, the team suggested that better understanding of this phenomenon could eventually improve malaria control.

They also pointed out that many other pathogens alternate between acute and dormant phases. So better understanding of the ecological determinants and evolutionary forces governing parasite relapses could have wide-ranging applications.

Plasmodium oocysts

(blue) in mosquito gut

Credit: Antoine Nicot

and Jacques Denoyelle

Experiments in canaries have shown that Plasmodium parasites react when non-infected mosquitoes bite their hosts, and the parasite responses increase transmission to the mosquito.

Like many other parasites, Plasmodium goes through a phase of chronic infection during which most of the parasites are in a dormant stage, and parasite numbers in the blood are very low.

Every now and then, however, the parasites “relapse,” and numbers increase, but the cause of this is not well understood.

So researchers set out to determine whether bites from non-infected mosquitoes can trigger relapses in Plasmodium during chronic infections, and whether relapses are associated with higher rates of transmission to the vector, ie, infection of the mosquitoes.

Sylvain Gandon, PhD, of the Université de Montpellier in France, and his colleagues described this research in PLOS Pathogens.

Specifically, the researchers studied the interaction between Plasmodium relictum, the parasite responsible for most cases of bird malaria in European songbirds, and its natural vector, a mosquito called Culex pipiens.

The team infected domestic canaries with P relictum and tested whether bites from uninfected Culex mosquitoes could trigger malaria relapses during chronic infection.

Indeed, parasite numbers in the blood routinely increased after the canaries were bitten. Moreover, the higher parasite loads following mosquito bites translated into higher infection rates in the mosquitoes.

The researchers therefore concluded that P relictum has the ability to boost its own transmission during the chronic phase of the vertebrate infection after being exposed to mosquito bites.

Although it is unclear if this also occurs in humans, the team suggested that better understanding of this phenomenon could eventually improve malaria control.

They also pointed out that many other pathogens alternate between acute and dormant phases. So better understanding of the ecological determinants and evolutionary forces governing parasite relapses could have wide-ranging applications.

Aspergillus fumigatus

WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.

Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).

The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.

Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).

Patient characteristics and safety outcomes

Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.

In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).

Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.

The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.

The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.

However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.

Response and mortality

All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.

All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.

For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.

In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.

“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.

ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.

The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.

Aspergillus fumigatus

WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.

Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).

The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.

Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).

Patient characteristics and safety outcomes

Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.

In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).

Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.

The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.

The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.

However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.

Response and mortality

All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.

All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.

For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.

In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.

“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.

ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.

The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.

Aspergillus fumigatus

WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.

Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).

The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.

Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).

Patient characteristics and safety outcomes

Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.

In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).

Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.

The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.

The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.

However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.

Response and mortality

All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.

All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.

For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.

In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.

“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.

ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.

The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.

Skin biopsy showing GVHD

Credit: PLOS ONE

Results of a retrospective study have revealed factors that appear to increase the risk of vitiligo and alopecia areata (AA) in patients who develop chronic graft-vs-host disease (cGVHD) after a stem cell transplant.

Multivariable analysis suggested that a female donor to male recipient sex mismatch and positive test results for anticardiolipin immunoglobulin G (ACA-IgG) were both significantly associated with vitiligo and/or AA.

This research was published in JAMA Dermatology.

Edward W. Cowen, MD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues conducted the study in 282 adult and pediatric patients with cGVHD.

Fifteen of the patients (5.3%) had vitiligo and/or AA. One patient had only AA, 1 had vitiligo and AA, and the rest had vitiligo alone. The median age of these patients at enrollment was 38 years (range, 9-69 years), and most were male (n=10).

Most patients had received a transplant to treat chronic myelogenous leukemia (n=5) or acute leukemia/myelodysplastic syndrome (n=5). Most patients (n=13) had an HLA-identical donor and received a peripheral blood stem cell transplant (n=9).

Eleven patients had concomitant skin cGVHD at the time of evaluation, and it was most often sclerotic-type cGVHD (n=9).

For the 5 vitiligo patients in whom the onset of skin depigmentation was documented, pigment changes occurred at a median of 41 months (range, 24-84) after transplant.

Depigmentation was classic periorbital, perioral, acrofacial involvement in 6 patients, generalized in 6 patients, and torso-predominant in 2 patients. Trichrome vitiligo was present in 3 patients, and poliosis occurred in 5 patients. In both AA patients, hair loss was localized to the scalp.

The researchers evaluated demographic, clinical, and laboratory data from these patients, and used univariate and multivariable logistic regression analyses to identify risk factors for vitiligo and AA.

Univariate analysis suggested the following factors were significantly associated with vitiligo and/or AA: female donor to male recipient sex mismatch (P=0.003), positive test results for ACA-IgG (P=0.03) or antiparietal antibody (P=0.049), elevated CD19 (P=0.045), and normal or elevated IgG (P=0.02).

However, only positive ACA-IgG results and female donor to male recipient mismatch retained significance in multivariable analysis (P=0.01 and P=0.003, respectively).

The researchers said additional studies are needed to clarify whether these risk factors can lead to a better understanding of the pathomechanisms of cGVHD.

Skin biopsy showing GVHD

Credit: PLOS ONE

Results of a retrospective study have revealed factors that appear to increase the risk of vitiligo and alopecia areata (AA) in patients who develop chronic graft-vs-host disease (cGVHD) after a stem cell transplant.

Multivariable analysis suggested that a female donor to male recipient sex mismatch and positive test results for anticardiolipin immunoglobulin G (ACA-IgG) were both significantly associated with vitiligo and/or AA.

This research was published in JAMA Dermatology.

Edward W. Cowen, MD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues conducted the study in 282 adult and pediatric patients with cGVHD.

Fifteen of the patients (5.3%) had vitiligo and/or AA. One patient had only AA, 1 had vitiligo and AA, and the rest had vitiligo alone. The median age of these patients at enrollment was 38 years (range, 9-69 years), and most were male (n=10).

Most patients had received a transplant to treat chronic myelogenous leukemia (n=5) or acute leukemia/myelodysplastic syndrome (n=5). Most patients (n=13) had an HLA-identical donor and received a peripheral blood stem cell transplant (n=9).

Eleven patients had concomitant skin cGVHD at the time of evaluation, and it was most often sclerotic-type cGVHD (n=9).

For the 5 vitiligo patients in whom the onset of skin depigmentation was documented, pigment changes occurred at a median of 41 months (range, 24-84) after transplant.

Depigmentation was classic periorbital, perioral, acrofacial involvement in 6 patients, generalized in 6 patients, and torso-predominant in 2 patients. Trichrome vitiligo was present in 3 patients, and poliosis occurred in 5 patients. In both AA patients, hair loss was localized to the scalp.

The researchers evaluated demographic, clinical, and laboratory data from these patients, and used univariate and multivariable logistic regression analyses to identify risk factors for vitiligo and AA.

Univariate analysis suggested the following factors were significantly associated with vitiligo and/or AA: female donor to male recipient sex mismatch (P=0.003), positive test results for ACA-IgG (P=0.03) or antiparietal antibody (P=0.049), elevated CD19 (P=0.045), and normal or elevated IgG (P=0.02).

However, only positive ACA-IgG results and female donor to male recipient mismatch retained significance in multivariable analysis (P=0.01 and P=0.003, respectively).

The researchers said additional studies are needed to clarify whether these risk factors can lead to a better understanding of the pathomechanisms of cGVHD.

Skin biopsy showing GVHD

Credit: PLOS ONE

Results of a retrospective study have revealed factors that appear to increase the risk of vitiligo and alopecia areata (AA) in patients who develop chronic graft-vs-host disease (cGVHD) after a stem cell transplant.

Multivariable analysis suggested that a female donor to male recipient sex mismatch and positive test results for anticardiolipin immunoglobulin G (ACA-IgG) were both significantly associated with vitiligo and/or AA.

This research was published in JAMA Dermatology.

Edward W. Cowen, MD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues conducted the study in 282 adult and pediatric patients with cGVHD.

Fifteen of the patients (5.3%) had vitiligo and/or AA. One patient had only AA, 1 had vitiligo and AA, and the rest had vitiligo alone. The median age of these patients at enrollment was 38 years (range, 9-69 years), and most were male (n=10).

Most patients had received a transplant to treat chronic myelogenous leukemia (n=5) or acute leukemia/myelodysplastic syndrome (n=5). Most patients (n=13) had an HLA-identical donor and received a peripheral blood stem cell transplant (n=9).

Eleven patients had concomitant skin cGVHD at the time of evaluation, and it was most often sclerotic-type cGVHD (n=9).

For the 5 vitiligo patients in whom the onset of skin depigmentation was documented, pigment changes occurred at a median of 41 months (range, 24-84) after transplant.

Depigmentation was classic periorbital, perioral, acrofacial involvement in 6 patients, generalized in 6 patients, and torso-predominant in 2 patients. Trichrome vitiligo was present in 3 patients, and poliosis occurred in 5 patients. In both AA patients, hair loss was localized to the scalp.

The researchers evaluated demographic, clinical, and laboratory data from these patients, and used univariate and multivariable logistic regression analyses to identify risk factors for vitiligo and AA.

Univariate analysis suggested the following factors were significantly associated with vitiligo and/or AA: female donor to male recipient sex mismatch (P=0.003), positive test results for ACA-IgG (P=0.03) or antiparietal antibody (P=0.049), elevated CD19 (P=0.045), and normal or elevated IgG (P=0.02).

However, only positive ACA-IgG results and female donor to male recipient mismatch retained significance in multivariable analysis (P=0.01 and P=0.003, respectively).

The researchers said additional studies are needed to clarify whether these risk factors can lead to a better understanding of the pathomechanisms of cGVHD. dermatology