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Donor EBV status affects recipient graft-vs-host disease risk
In allogeneic hematopoietic stem-cell transplantation, the donor’s status regarding Epstein-Barr virus affects the recipient’s risk of developing graft-vs-host disease – a “completely new and striking” finding, according to a report published online April 18 in the Journal of Clinical Oncology.
Approximately 80% of the general population has been infected with EBV and carries persistent virus in memory B cells. When viral material is transmitted to stem-cell recipients, it is known to cause posttransplantation lymphoproliferative disorder. Until now, however, no data were available to examine EBV serology’s effect on other posttransplantation outcomes, said Dr. Jan Styczynski of the department of pediatric hematology and oncology at Nicolaus Copernicus University, Bydgoszcz, Poland, and his associates.
They analyzed information in the European Society of Blood and Marrow Transplantation database for 11,364 patients with acute lymphoblastic leukemia or acute myeloblastic leukemia who underwent stem-cell transplantation between 1997 and 2012 and who were followed for approximately 5 years. Most of the donors (82%) were seropositive for EBV. Acute graft-vs-host disease (GVHD) developed in 32% and chronic GVHD developed in 40% of these stem cell–transplant recipients.
The incidence of chronic GVHD was significantly higher when the donor was EBV-seropositive (41%) than when the donor was EBV-seronegative (31%). Similarly, the incidence of acute GVHD was significantly higher when the donor was EBV-seropositive (32% vs 30%), but the magnitude of the difference between the two groups was smaller. The risk for GVHD increased even though patients receiving transplants from EBV-seropositive donors underwent more intensive GVHD prophylaxis than did those who had seronegative donors, the investigators said (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2015.64.2405).
In contrast, the transplant recipients’ EBV status did not affect their risk of developing GVHD.
“Despite the effect of donor EBV serostatus on GVHD, we did not observe a corresponding GVHD-related death rate, and as a result, there was no effect on overall survival, relapse-free survival, relapse incidence, and nonrelapse mortality. However, it should be kept in mind that many other pre- and posttransplantation factors play a role in contributing to final transplantation outcomes,” Dr. Styczynski and his associates noted.
The current recommendation to monitor transplantation recipients for EBV and to give them “preemptive” rituximab to stave off the development of posttransplantation lymphoproliferative disorder might prove useful in also preventing GVHD, they added.
The findings of Dr. Styczynski and his associates raise the possibility that we may be able to prevent or treat GVHD in transplant recipients by controlling EBV infection.
Selecting only EBV-negative donors would be one way to accomplish this, but that would be impractical given the high seroprevalence of EBV in the general population. Depleting memory B cells, the reservoir of EBV infection, using monoclonal antibodies may prove helpful, and these agents might provide additional therapeutic effects. And novel antivirals such as retroviral integrase inhibitors may be more specific at targeting EBV than acyclovir and related agents, which have limited activity against latently infected B cells. These novel drugs, however, are not without risks and adverse effects.
A promising alternative might be to boost immunity to EBV using vaccination or adoptive transfer of ex vivo expanded EBV-specific cytotoxic T cells.
Dr. Katayoun Rezvani and Dr. Richard E. Champlin are with the University of Texas MD Andersen Cancer Center, Houston. Their financial disclosures are available at www.jco.org. They made these remarks in an editorial accompanying Dr. Styczynski’s report (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2016.66.6099).
The findings of Dr. Styczynski and his associates raise the possibility that we may be able to prevent or treat GVHD in transplant recipients by controlling EBV infection.
Selecting only EBV-negative donors would be one way to accomplish this, but that would be impractical given the high seroprevalence of EBV in the general population. Depleting memory B cells, the reservoir of EBV infection, using monoclonal antibodies may prove helpful, and these agents might provide additional therapeutic effects. And novel antivirals such as retroviral integrase inhibitors may be more specific at targeting EBV than acyclovir and related agents, which have limited activity against latently infected B cells. These novel drugs, however, are not without risks and adverse effects.
A promising alternative might be to boost immunity to EBV using vaccination or adoptive transfer of ex vivo expanded EBV-specific cytotoxic T cells.
Dr. Katayoun Rezvani and Dr. Richard E. Champlin are with the University of Texas MD Andersen Cancer Center, Houston. Their financial disclosures are available at www.jco.org. They made these remarks in an editorial accompanying Dr. Styczynski’s report (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2016.66.6099).
The findings of Dr. Styczynski and his associates raise the possibility that we may be able to prevent or treat GVHD in transplant recipients by controlling EBV infection.
Selecting only EBV-negative donors would be one way to accomplish this, but that would be impractical given the high seroprevalence of EBV in the general population. Depleting memory B cells, the reservoir of EBV infection, using monoclonal antibodies may prove helpful, and these agents might provide additional therapeutic effects. And novel antivirals such as retroviral integrase inhibitors may be more specific at targeting EBV than acyclovir and related agents, which have limited activity against latently infected B cells. These novel drugs, however, are not without risks and adverse effects.
A promising alternative might be to boost immunity to EBV using vaccination or adoptive transfer of ex vivo expanded EBV-specific cytotoxic T cells.
Dr. Katayoun Rezvani and Dr. Richard E. Champlin are with the University of Texas MD Andersen Cancer Center, Houston. Their financial disclosures are available at www.jco.org. They made these remarks in an editorial accompanying Dr. Styczynski’s report (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2016.66.6099).
In allogeneic hematopoietic stem-cell transplantation, the donor’s status regarding Epstein-Barr virus affects the recipient’s risk of developing graft-vs-host disease – a “completely new and striking” finding, according to a report published online April 18 in the Journal of Clinical Oncology.
Approximately 80% of the general population has been infected with EBV and carries persistent virus in memory B cells. When viral material is transmitted to stem-cell recipients, it is known to cause posttransplantation lymphoproliferative disorder. Until now, however, no data were available to examine EBV serology’s effect on other posttransplantation outcomes, said Dr. Jan Styczynski of the department of pediatric hematology and oncology at Nicolaus Copernicus University, Bydgoszcz, Poland, and his associates.
They analyzed information in the European Society of Blood and Marrow Transplantation database for 11,364 patients with acute lymphoblastic leukemia or acute myeloblastic leukemia who underwent stem-cell transplantation between 1997 and 2012 and who were followed for approximately 5 years. Most of the donors (82%) were seropositive for EBV. Acute graft-vs-host disease (GVHD) developed in 32% and chronic GVHD developed in 40% of these stem cell–transplant recipients.
The incidence of chronic GVHD was significantly higher when the donor was EBV-seropositive (41%) than when the donor was EBV-seronegative (31%). Similarly, the incidence of acute GVHD was significantly higher when the donor was EBV-seropositive (32% vs 30%), but the magnitude of the difference between the two groups was smaller. The risk for GVHD increased even though patients receiving transplants from EBV-seropositive donors underwent more intensive GVHD prophylaxis than did those who had seronegative donors, the investigators said (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2015.64.2405).
In contrast, the transplant recipients’ EBV status did not affect their risk of developing GVHD.
“Despite the effect of donor EBV serostatus on GVHD, we did not observe a corresponding GVHD-related death rate, and as a result, there was no effect on overall survival, relapse-free survival, relapse incidence, and nonrelapse mortality. However, it should be kept in mind that many other pre- and posttransplantation factors play a role in contributing to final transplantation outcomes,” Dr. Styczynski and his associates noted.
The current recommendation to monitor transplantation recipients for EBV and to give them “preemptive” rituximab to stave off the development of posttransplantation lymphoproliferative disorder might prove useful in also preventing GVHD, they added.
In allogeneic hematopoietic stem-cell transplantation, the donor’s status regarding Epstein-Barr virus affects the recipient’s risk of developing graft-vs-host disease – a “completely new and striking” finding, according to a report published online April 18 in the Journal of Clinical Oncology.
Approximately 80% of the general population has been infected with EBV and carries persistent virus in memory B cells. When viral material is transmitted to stem-cell recipients, it is known to cause posttransplantation lymphoproliferative disorder. Until now, however, no data were available to examine EBV serology’s effect on other posttransplantation outcomes, said Dr. Jan Styczynski of the department of pediatric hematology and oncology at Nicolaus Copernicus University, Bydgoszcz, Poland, and his associates.
They analyzed information in the European Society of Blood and Marrow Transplantation database for 11,364 patients with acute lymphoblastic leukemia or acute myeloblastic leukemia who underwent stem-cell transplantation between 1997 and 2012 and who were followed for approximately 5 years. Most of the donors (82%) were seropositive for EBV. Acute graft-vs-host disease (GVHD) developed in 32% and chronic GVHD developed in 40% of these stem cell–transplant recipients.
The incidence of chronic GVHD was significantly higher when the donor was EBV-seropositive (41%) than when the donor was EBV-seronegative (31%). Similarly, the incidence of acute GVHD was significantly higher when the donor was EBV-seropositive (32% vs 30%), but the magnitude of the difference between the two groups was smaller. The risk for GVHD increased even though patients receiving transplants from EBV-seropositive donors underwent more intensive GVHD prophylaxis than did those who had seronegative donors, the investigators said (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2015.64.2405).
In contrast, the transplant recipients’ EBV status did not affect their risk of developing GVHD.
“Despite the effect of donor EBV serostatus on GVHD, we did not observe a corresponding GVHD-related death rate, and as a result, there was no effect on overall survival, relapse-free survival, relapse incidence, and nonrelapse mortality. However, it should be kept in mind that many other pre- and posttransplantation factors play a role in contributing to final transplantation outcomes,” Dr. Styczynski and his associates noted.
The current recommendation to monitor transplantation recipients for EBV and to give them “preemptive” rituximab to stave off the development of posttransplantation lymphoproliferative disorder might prove useful in also preventing GVHD, they added.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: In allogeneic hematopoietic stem-cell transplantation, the donor’s EBV status affects the recipient’s risk of developing GVHD.
Major finding: Chronic GVHD was significantly more likely to develop when the donor was EBV-seropositive (41%) than EBV-seronegative (31%).
Data source: A retrospective analysis of data regarding 11,364 European patients with acute leukemia who underwent stem-cell transplantation and were followed for 5 years.
Disclosures: No study sponsor was identified. Dr. Styczynski reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
Targeting T and B Cells as a Therapeutic Approach for Multiple Sclerosis
Immunotherapies that target abnormally activated T and B cells may represent a unique combination and promising DMT strategy for patients with RRMS and have the greatest potential for long-term success. Targeting T cells in MS may help attenuate initiation and maintenance of inflammatory attacks by reducing the production of pro-inflammatory cytokines, recruitment of innate immune cells, stimulation of antibody production, and direct attack of myelin. Targeting B cells in MS may attenuate secretion of autoantibodies and pro-inflammatory cytokines, as well as presentation of self-antigen to T cells.
Click here to read the digital edition.
Immunotherapies that target abnormally activated T and B cells may represent a unique combination and promising DMT strategy for patients with RRMS and have the greatest potential for long-term success. Targeting T cells in MS may help attenuate initiation and maintenance of inflammatory attacks by reducing the production of pro-inflammatory cytokines, recruitment of innate immune cells, stimulation of antibody production, and direct attack of myelin. Targeting B cells in MS may attenuate secretion of autoantibodies and pro-inflammatory cytokines, as well as presentation of self-antigen to T cells.
Click here to read the digital edition.
Immunotherapies that target abnormally activated T and B cells may represent a unique combination and promising DMT strategy for patients with RRMS and have the greatest potential for long-term success. Targeting T cells in MS may help attenuate initiation and maintenance of inflammatory attacks by reducing the production of pro-inflammatory cytokines, recruitment of innate immune cells, stimulation of antibody production, and direct attack of myelin. Targeting B cells in MS may attenuate secretion of autoantibodies and pro-inflammatory cytokines, as well as presentation of self-antigen to T cells.
Click here to read the digital edition.
U.S. flu activity down again, except in New Jersey
Overall activity of influenza-like illness (ILI) in the United States continued to fall, but New Jersey took a turn for the worse during the week ending April 9, 2016, according to the Centers for Disease Control and Prevention.
New Jersey’s ILI activity level went from 8 the previous week to 10 on the CDC’s 1-10 scale. For the week ending April 9, it was the only U.S. state in the “high” range, with Hawaii the next highest at level 6 – the only state in the “moderate” range, the CDC reported.
Nationwide, the proportion of outpatient visits for ILI was 2.1%, which is at the national baseline of 2.1% and down from 2.5% the week before. That number has now dropped for 4 consecutive weeks since hitting a season high of 3.7% for the week ending March 12. The CDC also reported a cumulative rate of 26.6 influenza-associated hospitalizations per 100,000 population.
Ten flu-related pediatric deaths were reported during the week, of which only one occurred during the week. A total of 50 flu-related pediatric deaths have been reported during the 2015-2016 season, the CDC said. The overall proportion of deaths attributed to pneumonia and influenza was below the system-specific threshold in the National Center for Health Statistics Mortality Surveillance System, but above the system-specific threshold in the 122 Cities Mortality Reporting System.
Overall activity of influenza-like illness (ILI) in the United States continued to fall, but New Jersey took a turn for the worse during the week ending April 9, 2016, according to the Centers for Disease Control and Prevention.
New Jersey’s ILI activity level went from 8 the previous week to 10 on the CDC’s 1-10 scale. For the week ending April 9, it was the only U.S. state in the “high” range, with Hawaii the next highest at level 6 – the only state in the “moderate” range, the CDC reported.
Nationwide, the proportion of outpatient visits for ILI was 2.1%, which is at the national baseline of 2.1% and down from 2.5% the week before. That number has now dropped for 4 consecutive weeks since hitting a season high of 3.7% for the week ending March 12. The CDC also reported a cumulative rate of 26.6 influenza-associated hospitalizations per 100,000 population.
Ten flu-related pediatric deaths were reported during the week, of which only one occurred during the week. A total of 50 flu-related pediatric deaths have been reported during the 2015-2016 season, the CDC said. The overall proportion of deaths attributed to pneumonia and influenza was below the system-specific threshold in the National Center for Health Statistics Mortality Surveillance System, but above the system-specific threshold in the 122 Cities Mortality Reporting System.
Overall activity of influenza-like illness (ILI) in the United States continued to fall, but New Jersey took a turn for the worse during the week ending April 9, 2016, according to the Centers for Disease Control and Prevention.
New Jersey’s ILI activity level went from 8 the previous week to 10 on the CDC’s 1-10 scale. For the week ending April 9, it was the only U.S. state in the “high” range, with Hawaii the next highest at level 6 – the only state in the “moderate” range, the CDC reported.
Nationwide, the proportion of outpatient visits for ILI was 2.1%, which is at the national baseline of 2.1% and down from 2.5% the week before. That number has now dropped for 4 consecutive weeks since hitting a season high of 3.7% for the week ending March 12. The CDC also reported a cumulative rate of 26.6 influenza-associated hospitalizations per 100,000 population.
Ten flu-related pediatric deaths were reported during the week, of which only one occurred during the week. A total of 50 flu-related pediatric deaths have been reported during the 2015-2016 season, the CDC said. The overall proportion of deaths attributed to pneumonia and influenza was below the system-specific threshold in the National Center for Health Statistics Mortality Surveillance System, but above the system-specific threshold in the 122 Cities Mortality Reporting System.
Pregnancy Considerations for Women With Epilepsy—The WEPOD Study
VANCOUVER—Women with epilepsy seeking pregnancy had comparable likelihood of achieving pregnancy, time to achieve pregnancy, and pregnancy outcomes, compared with a group of healthy peers, according to study findings presented at the 68th Annual Meeting of the American Academy of Neurology. "These findings should reassure women with epilepsy and clinicians when counseling women with epilepsy who are planning pregnancy," said Page B. Pennell, MD, Associate Professor of Neurology at Brigham and Women's Hospital and Harvard Medical School in Boston, and her research colleagues.
Page B. Pennell, MD, Associate Professor of Neurology at Brigham and Women's Hospital and Harvard Medical School in Boston, and her research colleagues.
Previous studies suggested that women with epilepsy have lower fertility compared with healthy controls. Dr. Pennell and colleagues sought to compare time to pregnancy and outcomes (eg, live birth, miscarriage) among women with epilepsy and healthy controls. The Women with Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study was a multicenter, prospective, observational study of women with epilepsy and healthy controls.
Dr. Pennell and colleagues enrolled and prospectively followed women with epilepsy and healthy controls, ages 18 to 41, seeking pregnancy within six months of discontinuing contraception. The customized WEPOD electronicdiary captured medication use, seizures, sexual activity, and menstrual bleeding. Pregnancy tests were performed if there was no menses by cycle day 35. Outcomes included proportions of women who achieved pregnancy and time to pregnancy from cessation of birth control. The researchers used a proportional hazard model to evaluate the association between time to pregnancy and certain baseline characteristics.
Enrolled in the study were 88 women with epilepsy and 109 healthy controls with similar demographic characteristics. Among women with epilepsy, 61.4% achieved pregnancy versus 60.6% for healthy controls. Median time to pregnancy was six months in women with epilepsy, compared with nine months for healthy controls. Time to pregnancy was no different across the two groups after controlling for age, BMI, parity, and race. Race and parity were significantly associated with time to pregnancy.
Of the pregnancies that occurred, a similar proportion resulted in miscarriage (12.9% among women with epilepsy and 19.7% among controls), live birth (80.0% among women with epilepsy and 80.3% controls) or other outcome (5.0% versus 0.0%).
The WEPOD study was supported by the Epilepsy Foundation.
VANCOUVER—Women with epilepsy seeking pregnancy had comparable likelihood of achieving pregnancy, time to achieve pregnancy, and pregnancy outcomes, compared with a group of healthy peers, according to study findings presented at the 68th Annual Meeting of the American Academy of Neurology. "These findings should reassure women with epilepsy and clinicians when counseling women with epilepsy who are planning pregnancy," said Page B. Pennell, MD, Associate Professor of Neurology at Brigham and Women's Hospital and Harvard Medical School in Boston, and her research colleagues.
Page B. Pennell, MD, Associate Professor of Neurology at Brigham and Women's Hospital and Harvard Medical School in Boston, and her research colleagues.
Previous studies suggested that women with epilepsy have lower fertility compared with healthy controls. Dr. Pennell and colleagues sought to compare time to pregnancy and outcomes (eg, live birth, miscarriage) among women with epilepsy and healthy controls. The Women with Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study was a multicenter, prospective, observational study of women with epilepsy and healthy controls.
Dr. Pennell and colleagues enrolled and prospectively followed women with epilepsy and healthy controls, ages 18 to 41, seeking pregnancy within six months of discontinuing contraception. The customized WEPOD electronicdiary captured medication use, seizures, sexual activity, and menstrual bleeding. Pregnancy tests were performed if there was no menses by cycle day 35. Outcomes included proportions of women who achieved pregnancy and time to pregnancy from cessation of birth control. The researchers used a proportional hazard model to evaluate the association between time to pregnancy and certain baseline characteristics.
Enrolled in the study were 88 women with epilepsy and 109 healthy controls with similar demographic characteristics. Among women with epilepsy, 61.4% achieved pregnancy versus 60.6% for healthy controls. Median time to pregnancy was six months in women with epilepsy, compared with nine months for healthy controls. Time to pregnancy was no different across the two groups after controlling for age, BMI, parity, and race. Race and parity were significantly associated with time to pregnancy.
Of the pregnancies that occurred, a similar proportion resulted in miscarriage (12.9% among women with epilepsy and 19.7% among controls), live birth (80.0% among women with epilepsy and 80.3% controls) or other outcome (5.0% versus 0.0%).
The WEPOD study was supported by the Epilepsy Foundation.
VANCOUVER—Women with epilepsy seeking pregnancy had comparable likelihood of achieving pregnancy, time to achieve pregnancy, and pregnancy outcomes, compared with a group of healthy peers, according to study findings presented at the 68th Annual Meeting of the American Academy of Neurology. "These findings should reassure women with epilepsy and clinicians when counseling women with epilepsy who are planning pregnancy," said Page B. Pennell, MD, Associate Professor of Neurology at Brigham and Women's Hospital and Harvard Medical School in Boston, and her research colleagues.
Page B. Pennell, MD, Associate Professor of Neurology at Brigham and Women's Hospital and Harvard Medical School in Boston, and her research colleagues.
Previous studies suggested that women with epilepsy have lower fertility compared with healthy controls. Dr. Pennell and colleagues sought to compare time to pregnancy and outcomes (eg, live birth, miscarriage) among women with epilepsy and healthy controls. The Women with Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study was a multicenter, prospective, observational study of women with epilepsy and healthy controls.
Dr. Pennell and colleagues enrolled and prospectively followed women with epilepsy and healthy controls, ages 18 to 41, seeking pregnancy within six months of discontinuing contraception. The customized WEPOD electronicdiary captured medication use, seizures, sexual activity, and menstrual bleeding. Pregnancy tests were performed if there was no menses by cycle day 35. Outcomes included proportions of women who achieved pregnancy and time to pregnancy from cessation of birth control. The researchers used a proportional hazard model to evaluate the association between time to pregnancy and certain baseline characteristics.
Enrolled in the study were 88 women with epilepsy and 109 healthy controls with similar demographic characteristics. Among women with epilepsy, 61.4% achieved pregnancy versus 60.6% for healthy controls. Median time to pregnancy was six months in women with epilepsy, compared with nine months for healthy controls. Time to pregnancy was no different across the two groups after controlling for age, BMI, parity, and race. Race and parity were significantly associated with time to pregnancy.
Of the pregnancies that occurred, a similar proportion resulted in miscarriage (12.9% among women with epilepsy and 19.7% among controls), live birth (80.0% among women with epilepsy and 80.3% controls) or other outcome (5.0% versus 0.0%).
The WEPOD study was supported by the Epilepsy Foundation.
VRIC is Just Around the Corner
The Vascular Research Initiatives Conference - VRIC - is less than three weeks away. The one-day conference, on May 4 in Nashville, focuses on translational research. This year’s theme is “Outside In: Paradigm Shifts in Vascular Disease.”
VRIC takes place the day before the American Heart Association’s Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) Scientific Sessions, and at the same venue in Nashville. VRIC is considered a key event for meeting and reconnecting with vascular research collaborators.
The Vascular Research Initiatives Conference - VRIC - is less than three weeks away. The one-day conference, on May 4 in Nashville, focuses on translational research. This year’s theme is “Outside In: Paradigm Shifts in Vascular Disease.”
VRIC takes place the day before the American Heart Association’s Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) Scientific Sessions, and at the same venue in Nashville. VRIC is considered a key event for meeting and reconnecting with vascular research collaborators.
The Vascular Research Initiatives Conference - VRIC - is less than three weeks away. The one-day conference, on May 4 in Nashville, focuses on translational research. This year’s theme is “Outside In: Paradigm Shifts in Vascular Disease.”
VRIC takes place the day before the American Heart Association’s Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) Scientific Sessions, and at the same venue in Nashville. VRIC is considered a key event for meeting and reconnecting with vascular research collaborators.
PCORI to Fund Pragmatic Trials and Studies
The Patient-Centered Outcomes Research Institute (PCORI) has announced new funding for pragmatic clinical trials, large simple trials or large-scale observational studies that compare the relative effectiveness of two or more alternatives for improving patient-centered outcomes.
Up to $1 million in direct costs for each study will be available through the initiative, “Pragmatic Clinical Studies to Evaluate Patient-Centered Outcomes.”
PCORI has a list of priority topics, though any study that addresses critical choices faced by patients, caregivers, clinicians and/or delivery systems will be considered.
Deadline for letters of intent is May 4. Application deadline is Aug. 8, and awards will be announced in January 2017.
The Patient-Centered Outcomes Research Institute (PCORI) has announced new funding for pragmatic clinical trials, large simple trials or large-scale observational studies that compare the relative effectiveness of two or more alternatives for improving patient-centered outcomes.
Up to $1 million in direct costs for each study will be available through the initiative, “Pragmatic Clinical Studies to Evaluate Patient-Centered Outcomes.”
PCORI has a list of priority topics, though any study that addresses critical choices faced by patients, caregivers, clinicians and/or delivery systems will be considered.
Deadline for letters of intent is May 4. Application deadline is Aug. 8, and awards will be announced in January 2017.
The Patient-Centered Outcomes Research Institute (PCORI) has announced new funding for pragmatic clinical trials, large simple trials or large-scale observational studies that compare the relative effectiveness of two or more alternatives for improving patient-centered outcomes.
Up to $1 million in direct costs for each study will be available through the initiative, “Pragmatic Clinical Studies to Evaluate Patient-Centered Outcomes.”
PCORI has a list of priority topics, though any study that addresses critical choices faced by patients, caregivers, clinicians and/or delivery systems will be considered.
Deadline for letters of intent is May 4. Application deadline is Aug. 8, and awards will be announced in January 2017.
Register for VAM Hands-On Workshops
SVS members have plenty of chances to learn by doing at hands-on workshops at the Vascular Annual Meeting. Twelve topics will be offered in four separate 90-minute sessions on Wednesday, June 8.
The workshops are $100 each (preregistration is required) and are not included in the VAM registration fee. Simply add the desired workshops when registering. Already registered? Just return to the registration page and add the workshops separately. The workshops are not eligible for CME credit.
Visit the VAM website for more information.
SVS members have plenty of chances to learn by doing at hands-on workshops at the Vascular Annual Meeting. Twelve topics will be offered in four separate 90-minute sessions on Wednesday, June 8.
The workshops are $100 each (preregistration is required) and are not included in the VAM registration fee. Simply add the desired workshops when registering. Already registered? Just return to the registration page and add the workshops separately. The workshops are not eligible for CME credit.
Visit the VAM website for more information.
SVS members have plenty of chances to learn by doing at hands-on workshops at the Vascular Annual Meeting. Twelve topics will be offered in four separate 90-minute sessions on Wednesday, June 8.
The workshops are $100 each (preregistration is required) and are not included in the VAM registration fee. Simply add the desired workshops when registering. Already registered? Just return to the registration page and add the workshops separately. The workshops are not eligible for CME credit.
Visit the VAM website for more information.
Edoxban has Advantages over Warfarin for Patients with Venous Thromboembolism
NEW YORK (Reuters Health) - Edoxaban (Savaysa, Daiichi-Sankyo) shows advantages over warfarin in long-term treatment of patients with venous thromboembolism (VTE), according to a post-hoc analysis of multinational trial data.
As Dr. Gary Raskob told Reuters Health by email, "Our results indicate that once-daily edoxaban provides an effective
and more convenient alternative to warfarin, with lower major bleeding risk, for patients who require extended treatment
beyond three months to prevent recurrent venous thromboembolism."
In a March 22 online paper in the Lancet Haematology, Dr.Raskob, of the University of Oklahoma, Oklahoma City, and colleagues note that guidelines recommend anticoagulant treatment for at least three months. However, "The risk of recurrence is substantial for patients with unprovoked venous thromboembolism or continuing risk factors and many of these
patients need extended anticoagulation therapy beyond three months."
To shed more light on longer term effects, the team examined outcome after three to 12 months in 3,633 patients treated with heparin and edoxaban and 3,594 treated with heparin and warfarin who took part in a randomized, double-blind trial. Median treatment duration was close to 9 months.
At three months, recurrent VTE was seen in 1.1% of the edoxaban group and 1.2% of the warfarin patients. At three to six months, the corresponding proportions were 0.7% and 0.5%. At more than six but less than 12 months, they were 0.2% and 0.8%.
Among other findings was that the cumulative incidence of major bleeding was 0.3% in the edoxaban-treated group and 0.7%
in the warfarin-treated patients. Intention-to-treat analysis gave similar results to these per-protocol findings.
Use of edoxaban, Dr. Raskob concluded, "may enable more patients to stay on extended anticoagulant treatment and help reduce the burden from recurrent venous thromboembolism."
Commenting on the findings by email, Dr. Jerrold H. Levy, coauthor of an accompanying editorial, told Reuters Health, "This post-hoc analysis reports that edoxaban is an alternative to warfarin for extended use in the secondary prevention of venous thromboembolism."
Dr. Levy, of Duke University Hospital, Durham, North Carolina, concluded, "The only other study where a direct oral anticoagulant was compared with warfarin for extended use in this setting was the RE-MEDY trial that compared dabigatran with warfarin in patients for six to 36 months and found dabigatran was similar to warfarin for efficacy with a lower incidence of clinically relevant major bleeding."
This study was funded by Daiichi-Sankyo. Dr. Raskob received fees from the company during the study. Other coauthors
also have ties to the company and a number are employees of Daiichi-Sankyo.
NEW YORK (Reuters Health) - Edoxaban (Savaysa, Daiichi-Sankyo) shows advantages over warfarin in long-term treatment of patients with venous thromboembolism (VTE), according to a post-hoc analysis of multinational trial data.
As Dr. Gary Raskob told Reuters Health by email, "Our results indicate that once-daily edoxaban provides an effective
and more convenient alternative to warfarin, with lower major bleeding risk, for patients who require extended treatment
beyond three months to prevent recurrent venous thromboembolism."
In a March 22 online paper in the Lancet Haematology, Dr.Raskob, of the University of Oklahoma, Oklahoma City, and colleagues note that guidelines recommend anticoagulant treatment for at least three months. However, "The risk of recurrence is substantial for patients with unprovoked venous thromboembolism or continuing risk factors and many of these
patients need extended anticoagulation therapy beyond three months."
To shed more light on longer term effects, the team examined outcome after three to 12 months in 3,633 patients treated with heparin and edoxaban and 3,594 treated with heparin and warfarin who took part in a randomized, double-blind trial. Median treatment duration was close to 9 months.
At three months, recurrent VTE was seen in 1.1% of the edoxaban group and 1.2% of the warfarin patients. At three to six months, the corresponding proportions were 0.7% and 0.5%. At more than six but less than 12 months, they were 0.2% and 0.8%.
Among other findings was that the cumulative incidence of major bleeding was 0.3% in the edoxaban-treated group and 0.7%
in the warfarin-treated patients. Intention-to-treat analysis gave similar results to these per-protocol findings.
Use of edoxaban, Dr. Raskob concluded, "may enable more patients to stay on extended anticoagulant treatment and help reduce the burden from recurrent venous thromboembolism."
Commenting on the findings by email, Dr. Jerrold H. Levy, coauthor of an accompanying editorial, told Reuters Health, "This post-hoc analysis reports that edoxaban is an alternative to warfarin for extended use in the secondary prevention of venous thromboembolism."
Dr. Levy, of Duke University Hospital, Durham, North Carolina, concluded, "The only other study where a direct oral anticoagulant was compared with warfarin for extended use in this setting was the RE-MEDY trial that compared dabigatran with warfarin in patients for six to 36 months and found dabigatran was similar to warfarin for efficacy with a lower incidence of clinically relevant major bleeding."
This study was funded by Daiichi-Sankyo. Dr. Raskob received fees from the company during the study. Other coauthors
also have ties to the company and a number are employees of Daiichi-Sankyo.
NEW YORK (Reuters Health) - Edoxaban (Savaysa, Daiichi-Sankyo) shows advantages over warfarin in long-term treatment of patients with venous thromboembolism (VTE), according to a post-hoc analysis of multinational trial data.
As Dr. Gary Raskob told Reuters Health by email, "Our results indicate that once-daily edoxaban provides an effective
and more convenient alternative to warfarin, with lower major bleeding risk, for patients who require extended treatment
beyond three months to prevent recurrent venous thromboembolism."
In a March 22 online paper in the Lancet Haematology, Dr.Raskob, of the University of Oklahoma, Oklahoma City, and colleagues note that guidelines recommend anticoagulant treatment for at least three months. However, "The risk of recurrence is substantial for patients with unprovoked venous thromboembolism or continuing risk factors and many of these
patients need extended anticoagulation therapy beyond three months."
To shed more light on longer term effects, the team examined outcome after three to 12 months in 3,633 patients treated with heparin and edoxaban and 3,594 treated with heparin and warfarin who took part in a randomized, double-blind trial. Median treatment duration was close to 9 months.
At three months, recurrent VTE was seen in 1.1% of the edoxaban group and 1.2% of the warfarin patients. At three to six months, the corresponding proportions were 0.7% and 0.5%. At more than six but less than 12 months, they were 0.2% and 0.8%.
Among other findings was that the cumulative incidence of major bleeding was 0.3% in the edoxaban-treated group and 0.7%
in the warfarin-treated patients. Intention-to-treat analysis gave similar results to these per-protocol findings.
Use of edoxaban, Dr. Raskob concluded, "may enable more patients to stay on extended anticoagulant treatment and help reduce the burden from recurrent venous thromboembolism."
Commenting on the findings by email, Dr. Jerrold H. Levy, coauthor of an accompanying editorial, told Reuters Health, "This post-hoc analysis reports that edoxaban is an alternative to warfarin for extended use in the secondary prevention of venous thromboembolism."
Dr. Levy, of Duke University Hospital, Durham, North Carolina, concluded, "The only other study where a direct oral anticoagulant was compared with warfarin for extended use in this setting was the RE-MEDY trial that compared dabigatran with warfarin in patients for six to 36 months and found dabigatran was similar to warfarin for efficacy with a lower incidence of clinically relevant major bleeding."
This study was funded by Daiichi-Sankyo. Dr. Raskob received fees from the company during the study. Other coauthors
also have ties to the company and a number are employees of Daiichi-Sankyo.
Hybrid drug could treat resistant malaria
Photo by James Gathany
A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.
With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.
For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.
One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.
Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).
In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.
The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.
The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.
Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.
Photo by James Gathany
A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.
With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.
For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.
One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.
Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).
In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.
The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.
The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.
Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.
Photo by James Gathany
A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.
With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.
For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.
One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.
Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).
In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.
The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.
The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.
Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.
Patients may be uninformed about risks of warfarin
ATHENS—A study of patients taking warfarin suggests many do not fully understand the risks associated with the drug.
Researchers asked patients to complete a questionnaire on warfarin use and found that, on average, patients answered 64% of the questions correctly.
The patients tended to be the least informed about food and drug interactions and which side effects necessitate a call or visit to the doctor.
Kjersti Oterhals, RN, PhD, of Haukeland University Hospital in Bergen, Norway, and her colleagues presented these findings at EuroHeartCare 2016 (abstract 36).
“The stroke and bleeding complications from warfarin can be fatal,” Dr Oterhals noted. “Worldwide, warfarin causes the most deaths from drug-related side effects. Patients need to know what foods and drugs have an impact on how warfarin works and what to do if they have symptoms of an overdose or underdose.”
Dr Oterhals and her colleagues evaluated warfarin knowledge in 404 patients with aortic stenosis. The patients’ mean age was 68, and 70% were male.
Nearly two-thirds of the patients (63%) were taking warfarin because they had a mechanical valve, and 24% were taking the drug because they had atrial fibrillation. The remaining patients were taking the drug for unknown reasons (6%) or “other” reasons (7%).
The patients received a postal questionnaire with 28 multiple-choice questions about warfarin. On average, patients answered 18 of the 28 questions correctly. However, 22% of patients answered less than half of the questions correctly.
The questions that were most often answered incorrectly were those concerning food and drug interactions and when to call or see a doctor.
For example, patients were asked which of the following foods would interfere with warfarin: celery, carrots, coleslaw, or green beans. Only 25% correctly said coleslaw. Most patients answered green beans.
“Patients often think green vegetables have the most vitamin K, but that’s not true,” Dr Oterhals said. “Brassica vegetables such as cabbage, broccoli, and cauliflower are rich sources.”
“Patients do not have to avoid these foods, but they should eat an equal amount every week because the vitamin K will decrease their INR and put them at increased risk of thrombosis or embolism. Patients who like to eat a lot of vitamin K-containing foods can take a higher warfarin dosage, but they need to be consistent.”
Dr Oterhals and her colleagues also found that 80% of patients knew they should go directly to the emergency room if they had nose bleeding that would not stop. However, only 45% of patients correctly said diarrhea for more than one day necessitates a visit to the doctor.
The study also showed that increased age was associated with a decrease in correct answers.
“We can only speculate why,” Dr Oterhals said. “Younger people tend to seek out information about how to manage their disease, while the older generation wants the doctor to tell them what to do.”
“Motivated patients should be offered an INR testing kit so that they can monitor their levels and adjust the warfarin dose themselves, just as patients with diabetes who use insulin do. It enables patients to travel and try new foods without having to find a clinic to get tested. Patients tell me that hot weather increases their INR, while another found out while in Asia that nori decreased his INR.”
“Warfarin is a life-saving drug but can be deadly if not used carefully. Health professionals have a responsibility to educate patients, but, unfortunately, even cardiac nurses do not know enough. There is an urgent need to improve health professionals’ warfarin knowledge so they can educate patients.”
ATHENS—A study of patients taking warfarin suggests many do not fully understand the risks associated with the drug.
Researchers asked patients to complete a questionnaire on warfarin use and found that, on average, patients answered 64% of the questions correctly.
The patients tended to be the least informed about food and drug interactions and which side effects necessitate a call or visit to the doctor.
Kjersti Oterhals, RN, PhD, of Haukeland University Hospital in Bergen, Norway, and her colleagues presented these findings at EuroHeartCare 2016 (abstract 36).
“The stroke and bleeding complications from warfarin can be fatal,” Dr Oterhals noted. “Worldwide, warfarin causes the most deaths from drug-related side effects. Patients need to know what foods and drugs have an impact on how warfarin works and what to do if they have symptoms of an overdose or underdose.”
Dr Oterhals and her colleagues evaluated warfarin knowledge in 404 patients with aortic stenosis. The patients’ mean age was 68, and 70% were male.
Nearly two-thirds of the patients (63%) were taking warfarin because they had a mechanical valve, and 24% were taking the drug because they had atrial fibrillation. The remaining patients were taking the drug for unknown reasons (6%) or “other” reasons (7%).
The patients received a postal questionnaire with 28 multiple-choice questions about warfarin. On average, patients answered 18 of the 28 questions correctly. However, 22% of patients answered less than half of the questions correctly.
The questions that were most often answered incorrectly were those concerning food and drug interactions and when to call or see a doctor.
For example, patients were asked which of the following foods would interfere with warfarin: celery, carrots, coleslaw, or green beans. Only 25% correctly said coleslaw. Most patients answered green beans.
“Patients often think green vegetables have the most vitamin K, but that’s not true,” Dr Oterhals said. “Brassica vegetables such as cabbage, broccoli, and cauliflower are rich sources.”
“Patients do not have to avoid these foods, but they should eat an equal amount every week because the vitamin K will decrease their INR and put them at increased risk of thrombosis or embolism. Patients who like to eat a lot of vitamin K-containing foods can take a higher warfarin dosage, but they need to be consistent.”
Dr Oterhals and her colleagues also found that 80% of patients knew they should go directly to the emergency room if they had nose bleeding that would not stop. However, only 45% of patients correctly said diarrhea for more than one day necessitates a visit to the doctor.
The study also showed that increased age was associated with a decrease in correct answers.
“We can only speculate why,” Dr Oterhals said. “Younger people tend to seek out information about how to manage their disease, while the older generation wants the doctor to tell them what to do.”
“Motivated patients should be offered an INR testing kit so that they can monitor their levels and adjust the warfarin dose themselves, just as patients with diabetes who use insulin do. It enables patients to travel and try new foods without having to find a clinic to get tested. Patients tell me that hot weather increases their INR, while another found out while in Asia that nori decreased his INR.”
“Warfarin is a life-saving drug but can be deadly if not used carefully. Health professionals have a responsibility to educate patients, but, unfortunately, even cardiac nurses do not know enough. There is an urgent need to improve health professionals’ warfarin knowledge so they can educate patients.”
ATHENS—A study of patients taking warfarin suggests many do not fully understand the risks associated with the drug.
Researchers asked patients to complete a questionnaire on warfarin use and found that, on average, patients answered 64% of the questions correctly.
The patients tended to be the least informed about food and drug interactions and which side effects necessitate a call or visit to the doctor.
Kjersti Oterhals, RN, PhD, of Haukeland University Hospital in Bergen, Norway, and her colleagues presented these findings at EuroHeartCare 2016 (abstract 36).
“The stroke and bleeding complications from warfarin can be fatal,” Dr Oterhals noted. “Worldwide, warfarin causes the most deaths from drug-related side effects. Patients need to know what foods and drugs have an impact on how warfarin works and what to do if they have symptoms of an overdose or underdose.”
Dr Oterhals and her colleagues evaluated warfarin knowledge in 404 patients with aortic stenosis. The patients’ mean age was 68, and 70% were male.
Nearly two-thirds of the patients (63%) were taking warfarin because they had a mechanical valve, and 24% were taking the drug because they had atrial fibrillation. The remaining patients were taking the drug for unknown reasons (6%) or “other” reasons (7%).
The patients received a postal questionnaire with 28 multiple-choice questions about warfarin. On average, patients answered 18 of the 28 questions correctly. However, 22% of patients answered less than half of the questions correctly.
The questions that were most often answered incorrectly were those concerning food and drug interactions and when to call or see a doctor.
For example, patients were asked which of the following foods would interfere with warfarin: celery, carrots, coleslaw, or green beans. Only 25% correctly said coleslaw. Most patients answered green beans.
“Patients often think green vegetables have the most vitamin K, but that’s not true,” Dr Oterhals said. “Brassica vegetables such as cabbage, broccoli, and cauliflower are rich sources.”
“Patients do not have to avoid these foods, but they should eat an equal amount every week because the vitamin K will decrease their INR and put them at increased risk of thrombosis or embolism. Patients who like to eat a lot of vitamin K-containing foods can take a higher warfarin dosage, but they need to be consistent.”
Dr Oterhals and her colleagues also found that 80% of patients knew they should go directly to the emergency room if they had nose bleeding that would not stop. However, only 45% of patients correctly said diarrhea for more than one day necessitates a visit to the doctor.
The study also showed that increased age was associated with a decrease in correct answers.
“We can only speculate why,” Dr Oterhals said. “Younger people tend to seek out information about how to manage their disease, while the older generation wants the doctor to tell them what to do.”
“Motivated patients should be offered an INR testing kit so that they can monitor their levels and adjust the warfarin dose themselves, just as patients with diabetes who use insulin do. It enables patients to travel and try new foods without having to find a clinic to get tested. Patients tell me that hot weather increases their INR, while another found out while in Asia that nori decreased his INR.”
“Warfarin is a life-saving drug but can be deadly if not used carefully. Health professionals have a responsibility to educate patients, but, unfortunately, even cardiac nurses do not know enough. There is an urgent need to improve health professionals’ warfarin knowledge so they can educate patients.”