Pediatricians have a central role in addressing the impact to children caused by armed conflict, including diagnosing and managing health conditions resulting from exposure to associated violence, according to a new American Academy of Pediatrics policy statement.

captain_galaxy/Thinkstock

The recommendation, published in Pediatrics, emphasizes the need for child health professionals to understand the prevalence of armed conflict and its pervasive effects on children and to respond both domestically and globally to the problem. The AAP defines armed conflict as any organized dispute that involves the use of weapons, violence, or force, such as international wars, civil wars, ethnic conflicts, and violence associated with gangs and drug trafficking. Children effected by armed conflict may include refugees forcibly displaced from their countries, unaccompanied immigrant children, and former child combatants, known as child soldiers.

The policy details the various health effects triggered by armed conflict, including physical, mental, developmental, and behavioral health conditions in children as well as indirect effects through deprivation and toxic stress. Children affected by armed conflict, for example, are at increased risk for PTSD, depression, anxiety, and behavioral and psychosomatic problems, which can continue well into adulthood, according to the policy statement.

To address these effects, pediatricians should receive training on trauma-informed care that enables them to recognize the dynamics of traumatic life experiences among children exposed to armed conflict and provide optimal responses, the policy advises.

Child health professionals who undergo trauma-informed care training are more sensitive in their responses to effected children and can work to mitigate the effects of trauma, according to the policy. The AAP recommends that child health professionals be prepared to diagnose and offer initial management for conditions associated with exposure to armed conflict as well as partner with community mental and behavioral health providers to establish collaborative care networks, when possible. Other AAP recommendations in the policy statement include that child health professionals:

• Be trained to provide “culturally effective care,” defined as “the delivery of care within the context of appropriate physician knowledge, understanding, and appreciation of all cultural distinctions, leading to optimal health outcomes.”
• Collaborate with local refugee resettlement groups and other public and private sector organizations, such as schools, health systems, and social services, to “facilitate the integration of children and families into their communities and to help families meet unmet needs.”‍
• Receive special preparation before working with refugees in camps or in conflict settings to become familiar with recognized standards for child protection and to better manage the physical, sexual, and psychological injuries caused by armed conflict.

The policy statement goes on to offer recommendations for systems that serve children exposed to armed conflict, advising that such systems should protect exposed children from abuse and exploitation, and offer access to physical, mental, behavioral, developmental, oral, and rehabilitation health services.

Finally, the AAP stressed its support of policies that advance the health, development, well-being, and rights of children affected by armed conflict and displacement. The AAP states that children should not be separated from their families during displacement and resettlement, emphasizing that “an intact family is the optimal environment for children’s health and well-being” and that “in the event of separation, family reunification should be prioritized.”

In addition, the AAP strongly advocates that children affected by armed conflict have access to educational opportunities, noting that pediatricians can act as a voice toward this end.

“There is strong evidence to suggest that education for boys and girls at all levels reduces most forms of political violence,” the authors wrote. “However, education currently receives less than 2% of all humanitarian funding, and girls are more likely than boys to be excluded from education. Because education is a priority for many children‍ and essential for their well-being, child health providers may advocate for their educational rights and access, especially during humanitarian emergencies.”

SOURCE: Shenoda S et al. Pediatrics. 2018 Nov 5. doi: 10.1542/peds.2018.2586.

Pediatricians have a central role in addressing the impact to children caused by armed conflict, including diagnosing and managing health conditions resulting from exposure to associated violence, according to a new American Academy of Pediatrics policy statement.

captain_galaxy/Thinkstock

The recommendation, published in Pediatrics, emphasizes the need for child health professionals to understand the prevalence of armed conflict and its pervasive effects on children and to respond both domestically and globally to the problem. The AAP defines armed conflict as any organized dispute that involves the use of weapons, violence, or force, such as international wars, civil wars, ethnic conflicts, and violence associated with gangs and drug trafficking. Children effected by armed conflict may include refugees forcibly displaced from their countries, unaccompanied immigrant children, and former child combatants, known as child soldiers.

The policy details the various health effects triggered by armed conflict, including physical, mental, developmental, and behavioral health conditions in children as well as indirect effects through deprivation and toxic stress. Children affected by armed conflict, for example, are at increased risk for PTSD, depression, anxiety, and behavioral and psychosomatic problems, which can continue well into adulthood, according to the policy statement.

To address these effects, pediatricians should receive training on trauma-informed care that enables them to recognize the dynamics of traumatic life experiences among children exposed to armed conflict and provide optimal responses, the policy advises.

Child health professionals who undergo trauma-informed care training are more sensitive in their responses to effected children and can work to mitigate the effects of trauma, according to the policy. The AAP recommends that child health professionals be prepared to diagnose and offer initial management for conditions associated with exposure to armed conflict as well as partner with community mental and behavioral health providers to establish collaborative care networks, when possible. Other AAP recommendations in the policy statement include that child health professionals:

• Be trained to provide “culturally effective care,” defined as “the delivery of care within the context of appropriate physician knowledge, understanding, and appreciation of all cultural distinctions, leading to optimal health outcomes.”
• Collaborate with local refugee resettlement groups and other public and private sector organizations, such as schools, health systems, and social services, to “facilitate the integration of children and families into their communities and to help families meet unmet needs.”‍
• Receive special preparation before working with refugees in camps or in conflict settings to become familiar with recognized standards for child protection and to better manage the physical, sexual, and psychological injuries caused by armed conflict.

The policy statement goes on to offer recommendations for systems that serve children exposed to armed conflict, advising that such systems should protect exposed children from abuse and exploitation, and offer access to physical, mental, behavioral, developmental, oral, and rehabilitation health services.

Finally, the AAP stressed its support of policies that advance the health, development, well-being, and rights of children affected by armed conflict and displacement. The AAP states that children should not be separated from their families during displacement and resettlement, emphasizing that “an intact family is the optimal environment for children’s health and well-being” and that “in the event of separation, family reunification should be prioritized.”

In addition, the AAP strongly advocates that children affected by armed conflict have access to educational opportunities, noting that pediatricians can act as a voice toward this end.

“There is strong evidence to suggest that education for boys and girls at all levels reduces most forms of political violence,” the authors wrote. “However, education currently receives less than 2% of all humanitarian funding, and girls are more likely than boys to be excluded from education. Because education is a priority for many children‍ and essential for their well-being, child health providers may advocate for their educational rights and access, especially during humanitarian emergencies.”

SOURCE: Shenoda S et al. Pediatrics. 2018 Nov 5. doi: 10.1542/peds.2018.2586.

Pediatricians have a central role in addressing the impact to children caused by armed conflict, including diagnosing and managing health conditions resulting from exposure to associated violence, according to a new American Academy of Pediatrics policy statement.

captain_galaxy/Thinkstock

The recommendation, published in Pediatrics, emphasizes the need for child health professionals to understand the prevalence of armed conflict and its pervasive effects on children and to respond both domestically and globally to the problem. The AAP defines armed conflict as any organized dispute that involves the use of weapons, violence, or force, such as international wars, civil wars, ethnic conflicts, and violence associated with gangs and drug trafficking. Children effected by armed conflict may include refugees forcibly displaced from their countries, unaccompanied immigrant children, and former child combatants, known as child soldiers.

The policy details the various health effects triggered by armed conflict, including physical, mental, developmental, and behavioral health conditions in children as well as indirect effects through deprivation and toxic stress. Children affected by armed conflict, for example, are at increased risk for PTSD, depression, anxiety, and behavioral and psychosomatic problems, which can continue well into adulthood, according to the policy statement.

To address these effects, pediatricians should receive training on trauma-informed care that enables them to recognize the dynamics of traumatic life experiences among children exposed to armed conflict and provide optimal responses, the policy advises.

Child health professionals who undergo trauma-informed care training are more sensitive in their responses to effected children and can work to mitigate the effects of trauma, according to the policy. The AAP recommends that child health professionals be prepared to diagnose and offer initial management for conditions associated with exposure to armed conflict as well as partner with community mental and behavioral health providers to establish collaborative care networks, when possible. Other AAP recommendations in the policy statement include that child health professionals:

• Be trained to provide “culturally effective care,” defined as “the delivery of care within the context of appropriate physician knowledge, understanding, and appreciation of all cultural distinctions, leading to optimal health outcomes.”
• Collaborate with local refugee resettlement groups and other public and private sector organizations, such as schools, health systems, and social services, to “facilitate the integration of children and families into their communities and to help families meet unmet needs.”‍
• Receive special preparation before working with refugees in camps or in conflict settings to become familiar with recognized standards for child protection and to better manage the physical, sexual, and psychological injuries caused by armed conflict.

The policy statement goes on to offer recommendations for systems that serve children exposed to armed conflict, advising that such systems should protect exposed children from abuse and exploitation, and offer access to physical, mental, behavioral, developmental, oral, and rehabilitation health services.

Finally, the AAP stressed its support of policies that advance the health, development, well-being, and rights of children affected by armed conflict and displacement. The AAP states that children should not be separated from their families during displacement and resettlement, emphasizing that “an intact family is the optimal environment for children’s health and well-being” and that “in the event of separation, family reunification should be prioritized.”

In addition, the AAP strongly advocates that children affected by armed conflict have access to educational opportunities, noting that pediatricians can act as a voice toward this end.

“There is strong evidence to suggest that education for boys and girls at all levels reduces most forms of political violence,” the authors wrote. “However, education currently receives less than 2% of all humanitarian funding, and girls are more likely than boys to be excluded from education. Because education is a priority for many children‍ and essential for their well-being, child health providers may advocate for their educational rights and access, especially during humanitarian emergencies.”

SOURCE: Shenoda S et al. Pediatrics. 2018 Nov 5. doi: 10.1542/peds.2018.2586.

While the American Medical Association (AMA) is the oldest and largest national medical association, many physicians, both CHEST members and nonmembers, have limited understanding of the policies, processes, and strategic foci of the AMA. It is our goal to inform our membership about the workings of the AMA and how those interact with the goals of CHEST and our members. We hope to do this by publishing periodic articles in CHEST Physician. One of the authors (DRM) was the CHEST delegate to the AMA for more than 20 years, and the other (NRD) is CHEST’s new AMA delegate. 

The American Medical Association (AMA) had its Annual Meeting of the House of Delegates (HOD) from May 9-13.  This meeting was attended by over 1,000 physicians who  are delegates from all geographic societies, ie, state societies and specialties and subspecialties, as well as the uniformed services. 

Policy and resolutions 

Process: 
Policies originate via resolutions submitted by individuals or societies.  These resolutions then go to one of several Reference Committees for open discussion.  These committees then report their recommendations back to the HOD, which then discusses and votes on the recommendations. In some instances, the question is referred for further studies by one of several Councils, which reports go to the Board of Trustees or back to the House.  The diagram below explains the flow of resolutions to policies.

Chest/Allergy Section Council  (which is composed of CHEST, ATS, SCCM, AASM, and several allergy specialty organizations) meets prior to the voting in the House to discuss the pending business. The Specialty and Service Society (SSS) is the largest caucus in the AMA’s House of Delegates and is composed of all the delegates from the specialty societies, as well as the uniformed services.  
There are two categories of groups in the SSS: those societies that have seats in the HOD and those seeking admission to the house.

SSS groups in the HOD include:
•    119 national medical specialties
•    2 professional interest medical associations
•    5 military or uniformed service groups (the Public Health Service is “uniformed” but not “military” or “armed”)

The compendium of policies covers the entire range of topics impacting the practice of medicine – ethics, legislation, regulation, public health, individual health, and medical education, among them.  The full range of policies can be found in the AMA’s Policy Manual available on the web site, AMA-assn.org

Some of the issues discussed at the HOD are as follows:
•    Health care as a “right.”  In response to a resolution asking the AMA to support health care as a “right,” the Board of Trustees reaffirmed current policy supporting expanded access to health care for all but stopped short of calling health care a “right.”
•    POLST forms. The Board of Trustees will work with state organizations and others to recognize Physician Orders for Life Sustaining Treatment (POLST) forms and allow for reciprocity between states.
•    Influenza vaccination. The HOD enacted as AMA policy that no health-care worker should be terminated from employment due solely to their refusal to be vaccinated for influenza. 
•    e-Cigarettes and tobacco.

A.    The AMA was instructed to urge federal officials, including but not limited to the US Food and Drug Administration (FDA), to prohibit the sale of any e-cigarette cartridge that does not include a complete list of ingredients on its packaging, in the order of prevalence (similar to food labeling). We will also urge federal officials, including but not limited to the FDA, to require that accurate nicotine content of e-cigarettes be prominently displayed on the product alongside a warning of the addictive quality of nicotine (new HOD policy). 

B.    Develop a report on the individual health and public health implications of a low nicotine standard for cigarettes. Such a report should consider and make recommendations on scientific criteria for selection of a nicotine standard that is nonaddictive, regulatory strategies to ensure compliance with an established standard, and how a low-nicotine standard should work with other nicotine products in a well-regulated nicotine market. American Medical Association consider joining other medical organizations in an amicus brief supporting the American Academy of Pediatrics legal action to compel the US Food and Drug Administration to take timely action to establish effective regulation of e-cigarettes, cigars, and other nicotine tobacco products (Directive to Take Action).

•    Prior authorization for durable medical equipment.  The AMA will advocate that denials of prior authorization for durable medical equipment must be based on true medical necessity not arbitrary time limits or other paperwork issues and will continue to work to improve the prior authorization process for Medicare Managed Care Plans (Directive to Take Action).
•    Medical training (including IMG, Medical students, Residents, and Fellows). 

A.    EHR and Business training during Med Ed and residency 

B.    Fellowship Start Date.  The AMA will survey physicians who have experienced a fellowship start date of August 1 to further evaluate the benefits and drawbacks from this transition (Directive to Take Action).

•    Opioid abuse. Surgeon General Jerome Adams addressed the HOD about several topics but focused on opioid crisis.
•    Physician Burnout and Organizational efficiency. Physician burnout is a health-care crisis in all specialties, and critical care has a very high rate of physician burnout. The AMA has several tools available that can help with physician burnout both in the ICU and outpatient medicine. (https://www.stepsforward.org)

This is just a small sampling of the activities at the HOD.  More information, including reports from the various Councils, are available on the AMA website, http://ama-assn.org. 

While the American Medical Association (AMA) is the oldest and largest national medical association, many physicians, both CHEST members and nonmembers, have limited understanding of the policies, processes, and strategic foci of the AMA. It is our goal to inform our membership about the workings of the AMA and how those interact with the goals of CHEST and our members. We hope to do this by publishing periodic articles in CHEST Physician. One of the authors (DRM) was the CHEST delegate to the AMA for more than 20 years, and the other (NRD) is CHEST’s new AMA delegate. 

The American Medical Association (AMA) had its Annual Meeting of the House of Delegates (HOD) from May 9-13.  This meeting was attended by over 1,000 physicians who  are delegates from all geographic societies, ie, state societies and specialties and subspecialties, as well as the uniformed services. 

Policy and resolutions 

Process: 
Policies originate via resolutions submitted by individuals or societies.  These resolutions then go to one of several Reference Committees for open discussion.  These committees then report their recommendations back to the HOD, which then discusses and votes on the recommendations. In some instances, the question is referred for further studies by one of several Councils, which reports go to the Board of Trustees or back to the House.  The diagram below explains the flow of resolutions to policies.

Chest/Allergy Section Council  (which is composed of CHEST, ATS, SCCM, AASM, and several allergy specialty organizations) meets prior to the voting in the House to discuss the pending business. The Specialty and Service Society (SSS) is the largest caucus in the AMA’s House of Delegates and is composed of all the delegates from the specialty societies, as well as the uniformed services.  
There are two categories of groups in the SSS: those societies that have seats in the HOD and those seeking admission to the house.

SSS groups in the HOD include:
•    119 national medical specialties
•    2 professional interest medical associations
•    5 military or uniformed service groups (the Public Health Service is “uniformed” but not “military” or “armed”)

The compendium of policies covers the entire range of topics impacting the practice of medicine – ethics, legislation, regulation, public health, individual health, and medical education, among them.  The full range of policies can be found in the AMA’s Policy Manual available on the web site, AMA-assn.org

Some of the issues discussed at the HOD are as follows:
•    Health care as a “right.”  In response to a resolution asking the AMA to support health care as a “right,” the Board of Trustees reaffirmed current policy supporting expanded access to health care for all but stopped short of calling health care a “right.”
•    POLST forms. The Board of Trustees will work with state organizations and others to recognize Physician Orders for Life Sustaining Treatment (POLST) forms and allow for reciprocity between states.
•    Influenza vaccination. The HOD enacted as AMA policy that no health-care worker should be terminated from employment due solely to their refusal to be vaccinated for influenza. 
•    e-Cigarettes and tobacco.

A.    The AMA was instructed to urge federal officials, including but not limited to the US Food and Drug Administration (FDA), to prohibit the sale of any e-cigarette cartridge that does not include a complete list of ingredients on its packaging, in the order of prevalence (similar to food labeling). We will also urge federal officials, including but not limited to the FDA, to require that accurate nicotine content of e-cigarettes be prominently displayed on the product alongside a warning of the addictive quality of nicotine (new HOD policy). 

B.    Develop a report on the individual health and public health implications of a low nicotine standard for cigarettes. Such a report should consider and make recommendations on scientific criteria for selection of a nicotine standard that is nonaddictive, regulatory strategies to ensure compliance with an established standard, and how a low-nicotine standard should work with other nicotine products in a well-regulated nicotine market. American Medical Association consider joining other medical organizations in an amicus brief supporting the American Academy of Pediatrics legal action to compel the US Food and Drug Administration to take timely action to establish effective regulation of e-cigarettes, cigars, and other nicotine tobacco products (Directive to Take Action).

•    Prior authorization for durable medical equipment.  The AMA will advocate that denials of prior authorization for durable medical equipment must be based on true medical necessity not arbitrary time limits or other paperwork issues and will continue to work to improve the prior authorization process for Medicare Managed Care Plans (Directive to Take Action).
•    Medical training (including IMG, Medical students, Residents, and Fellows). 

A.    EHR and Business training during Med Ed and residency 

B.    Fellowship Start Date.  The AMA will survey physicians who have experienced a fellowship start date of August 1 to further evaluate the benefits and drawbacks from this transition (Directive to Take Action).

•    Opioid abuse. Surgeon General Jerome Adams addressed the HOD about several topics but focused on opioid crisis.
•    Physician Burnout and Organizational efficiency. Physician burnout is a health-care crisis in all specialties, and critical care has a very high rate of physician burnout. The AMA has several tools available that can help with physician burnout both in the ICU and outpatient medicine. (https://www.stepsforward.org)

This is just a small sampling of the activities at the HOD.  More information, including reports from the various Councils, are available on the AMA website, http://ama-assn.org. 

While the American Medical Association (AMA) is the oldest and largest national medical association, many physicians, both CHEST members and nonmembers, have limited understanding of the policies, processes, and strategic foci of the AMA. It is our goal to inform our membership about the workings of the AMA and how those interact with the goals of CHEST and our members. We hope to do this by publishing periodic articles in CHEST Physician. One of the authors (DRM) was the CHEST delegate to the AMA for more than 20 years, and the other (NRD) is CHEST’s new AMA delegate. 

The American Medical Association (AMA) had its Annual Meeting of the House of Delegates (HOD) from May 9-13.  This meeting was attended by over 1,000 physicians who  are delegates from all geographic societies, ie, state societies and specialties and subspecialties, as well as the uniformed services. 

Policy and resolutions 

Process: 
Policies originate via resolutions submitted by individuals or societies.  These resolutions then go to one of several Reference Committees for open discussion.  These committees then report their recommendations back to the HOD, which then discusses and votes on the recommendations. In some instances, the question is referred for further studies by one of several Councils, which reports go to the Board of Trustees or back to the House.  The diagram below explains the flow of resolutions to policies.

Chest/Allergy Section Council  (which is composed of CHEST, ATS, SCCM, AASM, and several allergy specialty organizations) meets prior to the voting in the House to discuss the pending business. The Specialty and Service Society (SSS) is the largest caucus in the AMA’s House of Delegates and is composed of all the delegates from the specialty societies, as well as the uniformed services.  
There are two categories of groups in the SSS: those societies that have seats in the HOD and those seeking admission to the house.

SSS groups in the HOD include:
•    119 national medical specialties
•    2 professional interest medical associations
•    5 military or uniformed service groups (the Public Health Service is “uniformed” but not “military” or “armed”)

The compendium of policies covers the entire range of topics impacting the practice of medicine – ethics, legislation, regulation, public health, individual health, and medical education, among them.  The full range of policies can be found in the AMA’s Policy Manual available on the web site, AMA-assn.org

Some of the issues discussed at the HOD are as follows:
•    Health care as a “right.”  In response to a resolution asking the AMA to support health care as a “right,” the Board of Trustees reaffirmed current policy supporting expanded access to health care for all but stopped short of calling health care a “right.”
•    POLST forms. The Board of Trustees will work with state organizations and others to recognize Physician Orders for Life Sustaining Treatment (POLST) forms and allow for reciprocity between states.
•    Influenza vaccination. The HOD enacted as AMA policy that no health-care worker should be terminated from employment due solely to their refusal to be vaccinated for influenza. 
•    e-Cigarettes and tobacco.

A.    The AMA was instructed to urge federal officials, including but not limited to the US Food and Drug Administration (FDA), to prohibit the sale of any e-cigarette cartridge that does not include a complete list of ingredients on its packaging, in the order of prevalence (similar to food labeling). We will also urge federal officials, including but not limited to the FDA, to require that accurate nicotine content of e-cigarettes be prominently displayed on the product alongside a warning of the addictive quality of nicotine (new HOD policy). 

B.    Develop a report on the individual health and public health implications of a low nicotine standard for cigarettes. Such a report should consider and make recommendations on scientific criteria for selection of a nicotine standard that is nonaddictive, regulatory strategies to ensure compliance with an established standard, and how a low-nicotine standard should work with other nicotine products in a well-regulated nicotine market. American Medical Association consider joining other medical organizations in an amicus brief supporting the American Academy of Pediatrics legal action to compel the US Food and Drug Administration to take timely action to establish effective regulation of e-cigarettes, cigars, and other nicotine tobacco products (Directive to Take Action).

•    Prior authorization for durable medical equipment.  The AMA will advocate that denials of prior authorization for durable medical equipment must be based on true medical necessity not arbitrary time limits or other paperwork issues and will continue to work to improve the prior authorization process for Medicare Managed Care Plans (Directive to Take Action).
•    Medical training (including IMG, Medical students, Residents, and Fellows). 

A.    EHR and Business training during Med Ed and residency 

B.    Fellowship Start Date.  The AMA will survey physicians who have experienced a fellowship start date of August 1 to further evaluate the benefits and drawbacks from this transition (Directive to Take Action).

•    Opioid abuse. Surgeon General Jerome Adams addressed the HOD about several topics but focused on opioid crisis.
•    Physician Burnout and Organizational efficiency. Physician burnout is a health-care crisis in all specialties, and critical care has a very high rate of physician burnout. The AMA has several tools available that can help with physician burnout both in the ICU and outpatient medicine. (https://www.stepsforward.org)

This is just a small sampling of the activities at the HOD.  More information, including reports from the various Councils, are available on the AMA website, http://ama-assn.org. 

Unless someone has already had a heart attack or other cardiovascular event, daily low-dose aspirin does not prolong healthy independent living, according to the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

The study began in 2010, enrolling 19,114 adults aged ≥ 65 years. The participants were treated with 100 mg/d of aspirin or placebo and followed for an average of 4.7 years. Of participants randomly assigned aspirin, 90.3% were still alive at the end of the treatment without persistent physical disability or dementia, as were 90.5% of those on placebo. Rates of dementia were almost identical in both groups. Major cardiovascular events were similar: 448 in the aspirin group and 474 in the placebo group.

The aspirin group had a slightly higher risk of death (5.9% vs 5.2%). The researchers advise interpreting this cautiously: Most of the deaths were due to cancer. A small increase in new cases of cancer was reported for the aspirin group but may have been due to chance. Heart disease accounted for 19% of deaths and major bleeding for 5%. People taking aspirin were more likely to have significant bleeding (3.8% vs 2.7%).

The researchers emphasize that, study findings notwithstanding, older adults should follow their physician’s advice about daily aspirin use. The new findings do not apply to people with an indication for aspirin, including stroke, heart attack, or other cardiovascular disease.

Unless someone has already had a heart attack or other cardiovascular event, daily low-dose aspirin does not prolong healthy independent living, according to the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

The study began in 2010, enrolling 19,114 adults aged ≥ 65 years. The participants were treated with 100 mg/d of aspirin or placebo and followed for an average of 4.7 years. Of participants randomly assigned aspirin, 90.3% were still alive at the end of the treatment without persistent physical disability or dementia, as were 90.5% of those on placebo. Rates of dementia were almost identical in both groups. Major cardiovascular events were similar: 448 in the aspirin group and 474 in the placebo group.

The aspirin group had a slightly higher risk of death (5.9% vs 5.2%). The researchers advise interpreting this cautiously: Most of the deaths were due to cancer. A small increase in new cases of cancer was reported for the aspirin group but may have been due to chance. Heart disease accounted for 19% of deaths and major bleeding for 5%. People taking aspirin were more likely to have significant bleeding (3.8% vs 2.7%).

The researchers emphasize that, study findings notwithstanding, older adults should follow their physician’s advice about daily aspirin use. The new findings do not apply to people with an indication for aspirin, including stroke, heart attack, or other cardiovascular disease.

Unless someone has already had a heart attack or other cardiovascular event, daily low-dose aspirin does not prolong healthy independent living, according to the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

The study began in 2010, enrolling 19,114 adults aged ≥ 65 years. The participants were treated with 100 mg/d of aspirin or placebo and followed for an average of 4.7 years. Of participants randomly assigned aspirin, 90.3% were still alive at the end of the treatment without persistent physical disability or dementia, as were 90.5% of those on placebo. Rates of dementia were almost identical in both groups. Major cardiovascular events were similar: 448 in the aspirin group and 474 in the placebo group.

The aspirin group had a slightly higher risk of death (5.9% vs 5.2%). The researchers advise interpreting this cautiously: Most of the deaths were due to cancer. A small increase in new cases of cancer was reported for the aspirin group but may have been due to chance. Heart disease accounted for 19% of deaths and major bleeding for 5%. People taking aspirin were more likely to have significant bleeding (3.8% vs 2.7%).

The researchers emphasize that, study findings notwithstanding, older adults should follow their physician’s advice about daily aspirin use. The new findings do not apply to people with an indication for aspirin, including stroke, heart attack, or other cardiovascular disease.

follicular lymphoma

The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.

Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.

In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.

Most of the responses were ongoing at the time of data cutoff.

“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.

She and her colleagues reported these results in The New England Journal of Medicine.

The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).

The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).

All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.

Patients received rituximab at 375 mg/m² weekly starting on the second week of the first cycle and then monthly for cycles two through six.

Results

The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).

Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).

For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).

Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).

The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.

Ten of 11 responders (91%) were still in response at the time of data cutoff.

The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.

The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.

follicular lymphoma

The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.

Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.

In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.

Most of the responses were ongoing at the time of data cutoff.

“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.

She and her colleagues reported these results in The New England Journal of Medicine.

The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).

The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).

All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.

Patients received rituximab at 375 mg/m² weekly starting on the second week of the first cycle and then monthly for cycles two through six.

Results

The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).

Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).

For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).

Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).

The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.

Ten of 11 responders (91%) were still in response at the time of data cutoff.

The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.

The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.

follicular lymphoma

The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.

Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.

In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.

Most of the responses were ongoing at the time of data cutoff.

“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.

She and her colleagues reported these results in The New England Journal of Medicine.

The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).

The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).

All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.

Patients received rituximab at 375 mg/m² weekly starting on the second week of the first cycle and then monthly for cycles two through six.

Results

The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).

Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).

For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).

Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).

The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.

Ten of 11 responders (91%) were still in response at the time of data cutoff.

The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.

The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.

AML cells

New research suggests relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT) is related to changes in immune-related gene expression that may be reversible.

Researchers observed downregulation of major histocompatibility complex (MHC) class II genes in samples from patients who relapsed after HSCT.

However, interferon-gamma “rapidly reversed this phenotype” in vitro, according to the researchers.

Matthew J. Christopher, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri, and his colleagues reported these findings in The New England Journal of Medicine.

The researchers set out to determine how genetic and epigenetic changes after HSCT may allow leukemic cells to avoid the graft-vs-leukemia effect and to see whether immune-related genes are affected by HSCT.

The team analyzed paired samples obtained at diagnosis and relapse from 15 AML patients who relapsed after HSCT and 20 AML patients who relapsed after chemotherapy. The team also analyzed additional samples from patients who relapsed after HSCT to validate initial findings.

Methods of analysis included enhanced exome sequencing, RNA sequencing, flow cytometry, and immunohistochemical analysis.

Findings

The researchers first looked for relapse-specific mutations but found no driver mutations associated with relapse after HSCT.

The mutations seen post-HSCT relapse were generally similar to those seen both before treatment and after relapse in patients who had undergone chemotherapy, and the researchers could not identify any patterns of mutations related to relapse.

They then looked for, but did not find, relapse-specific mutations in genes involved in modulation of immune checkpoints, antigen presentation, or cytokine signaling.

The researchers did, however, find evidence of epigenetic changes that were more common in the samples from patients with post-transplant relapses.

RNA sequencing showed that MHC class II genes (HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) were downregulated three- to 12-fold after transplant.

Flow cytometry and immunohistochemical analysis confirmed that MHC class II expression was decreased at relapse after HSCT in 17 of 34 samples evaluated.

The researchers said there was no association between the downregulation of MHC class II and donor type or use of immunosuppression.

To see whether the downregulation of MHC class II genes was reversible, the researchers treated three post-HSCT relapse samples with interferon-gamma, which is known to upregulate MHC class II on certain cells.

Culturing patient cells with interferon-gamma “rapidly induced MHC class II protein expression on leukemic blasts,” the researchers said. They observed “essentially full restoration of MHC class II protein expression in nearly all AML blasts after 72 hours.”

This study was supported by the National Institutes of Health, Leukemia and Lymphoma Society, and the Barnes-Jewish Hospital Foundation.

Several study authors reported personal fees and/or research support from industry outside the submitted work.

AML cells

New research suggests relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT) is related to changes in immune-related gene expression that may be reversible.

Researchers observed downregulation of major histocompatibility complex (MHC) class II genes in samples from patients who relapsed after HSCT.

However, interferon-gamma “rapidly reversed this phenotype” in vitro, according to the researchers.

Matthew J. Christopher, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri, and his colleagues reported these findings in The New England Journal of Medicine.

The researchers set out to determine how genetic and epigenetic changes after HSCT may allow leukemic cells to avoid the graft-vs-leukemia effect and to see whether immune-related genes are affected by HSCT.

The team analyzed paired samples obtained at diagnosis and relapse from 15 AML patients who relapsed after HSCT and 20 AML patients who relapsed after chemotherapy. The team also analyzed additional samples from patients who relapsed after HSCT to validate initial findings.

Methods of analysis included enhanced exome sequencing, RNA sequencing, flow cytometry, and immunohistochemical analysis.

Findings

The researchers first looked for relapse-specific mutations but found no driver mutations associated with relapse after HSCT.

The mutations seen post-HSCT relapse were generally similar to those seen both before treatment and after relapse in patients who had undergone chemotherapy, and the researchers could not identify any patterns of mutations related to relapse.

They then looked for, but did not find, relapse-specific mutations in genes involved in modulation of immune checkpoints, antigen presentation, or cytokine signaling.

The researchers did, however, find evidence of epigenetic changes that were more common in the samples from patients with post-transplant relapses.

RNA sequencing showed that MHC class II genes (HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) were downregulated three- to 12-fold after transplant.

Flow cytometry and immunohistochemical analysis confirmed that MHC class II expression was decreased at relapse after HSCT in 17 of 34 samples evaluated.

The researchers said there was no association between the downregulation of MHC class II and donor type or use of immunosuppression.

To see whether the downregulation of MHC class II genes was reversible, the researchers treated three post-HSCT relapse samples with interferon-gamma, which is known to upregulate MHC class II on certain cells.

Culturing patient cells with interferon-gamma “rapidly induced MHC class II protein expression on leukemic blasts,” the researchers said. They observed “essentially full restoration of MHC class II protein expression in nearly all AML blasts after 72 hours.”

This study was supported by the National Institutes of Health, Leukemia and Lymphoma Society, and the Barnes-Jewish Hospital Foundation.

Several study authors reported personal fees and/or research support from industry outside the submitted work.

AML cells

New research suggests relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT) is related to changes in immune-related gene expression that may be reversible.

Researchers observed downregulation of major histocompatibility complex (MHC) class II genes in samples from patients who relapsed after HSCT.

However, interferon-gamma “rapidly reversed this phenotype” in vitro, according to the researchers.

Matthew J. Christopher, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri, and his colleagues reported these findings in The New England Journal of Medicine.

The researchers set out to determine how genetic and epigenetic changes after HSCT may allow leukemic cells to avoid the graft-vs-leukemia effect and to see whether immune-related genes are affected by HSCT.

The team analyzed paired samples obtained at diagnosis and relapse from 15 AML patients who relapsed after HSCT and 20 AML patients who relapsed after chemotherapy. The team also analyzed additional samples from patients who relapsed after HSCT to validate initial findings.

Methods of analysis included enhanced exome sequencing, RNA sequencing, flow cytometry, and immunohistochemical analysis.

Findings

The researchers first looked for relapse-specific mutations but found no driver mutations associated with relapse after HSCT.

The mutations seen post-HSCT relapse were generally similar to those seen both before treatment and after relapse in patients who had undergone chemotherapy, and the researchers could not identify any patterns of mutations related to relapse.

They then looked for, but did not find, relapse-specific mutations in genes involved in modulation of immune checkpoints, antigen presentation, or cytokine signaling.

The researchers did, however, find evidence of epigenetic changes that were more common in the samples from patients with post-transplant relapses.

RNA sequencing showed that MHC class II genes (HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) were downregulated three- to 12-fold after transplant.

Flow cytometry and immunohistochemical analysis confirmed that MHC class II expression was decreased at relapse after HSCT in 17 of 34 samples evaluated.

The researchers said there was no association between the downregulation of MHC class II and donor type or use of immunosuppression.

To see whether the downregulation of MHC class II genes was reversible, the researchers treated three post-HSCT relapse samples with interferon-gamma, which is known to upregulate MHC class II on certain cells.

Culturing patient cells with interferon-gamma “rapidly induced MHC class II protein expression on leukemic blasts,” the researchers said. They observed “essentially full restoration of MHC class II protein expression in nearly all AML blasts after 72 hours.”

This study was supported by the National Institutes of Health, Leukemia and Lymphoma Society, and the Barnes-Jewish Hospital Foundation.

Several study authors reported personal fees and/or research support from industry outside the submitted work.

Vials and a syringe

Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.

GP2013 (Rixathon, Riximyo) is already approved outside the U.S.

Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.

In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.

At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.

“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.

“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”

The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.

The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.

At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.

Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.

The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.

Vials and a syringe

Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.

GP2013 (Rixathon, Riximyo) is already approved outside the U.S.

Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.

In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.

At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.

“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.

“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”

The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.

The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.

At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.

Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.

The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.

Vials and a syringe

Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.

GP2013 (Rixathon, Riximyo) is already approved outside the U.S.

Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.

In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.

At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.

“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.

“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”

The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.

The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.

At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.

Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.

The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.

Micrograph showing myelofibrosis

The U.S. Food and Drug Administration (FDA) has granted fast track designation to CPI-0610 for the treatment of myelofibrosis (MF).

CPI-0610 is a BET inhibitor being developed by Constellation Pharmaceuticals, Inc.

The company said results from preclinical studies and translational insights from the first-in-human study of CPI-0610 led to the prioritization of CPI-0610 as a potential treatment for MF.

The company is now enrolling patients in the phase 2 portion of the phase 1/2 MANIFEST trial (NCT02158858).

In this trial, researchers are testing CPI-0610 alone or in combination with ruxolitinib in the following patient groups:

• Transfusion-dependent or -independent MF patients who have previously received a JAK inhibitor and are ineligible for or cannot tolerate additional JAK inhibitor therapy, lost response to a JAK inhibitor, or are resistant or refractory to JAK inhibition
• MF patients who are transfusion-dependent or -independent whose disease is not being adequately controlled by ruxolitinib
• MF patients who are anemic and have not previously received a JAK inhibitor.

According to Constellation Pharmaceuticals, CPI-0610 demonstrated clinical activity in the first four patients treated on this trial, all of whom previously received a JAK inhibitor.

The researchers observed reductions in spleen volume and improvements in hemoglobin levels in patients who received monotherapy (n=2) or CPI-0610 plus ruxolitinib (n=2).

One patient treated with the combination experienced resolution of thrombocytosis and became transfusion-independent.

The company said proof-of-concept data from this trial are expected in mid-2019.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Micrograph showing myelofibrosis

The U.S. Food and Drug Administration (FDA) has granted fast track designation to CPI-0610 for the treatment of myelofibrosis (MF).

CPI-0610 is a BET inhibitor being developed by Constellation Pharmaceuticals, Inc.

The company said results from preclinical studies and translational insights from the first-in-human study of CPI-0610 led to the prioritization of CPI-0610 as a potential treatment for MF.

The company is now enrolling patients in the phase 2 portion of the phase 1/2 MANIFEST trial (NCT02158858).

In this trial, researchers are testing CPI-0610 alone or in combination with ruxolitinib in the following patient groups:

• Transfusion-dependent or -independent MF patients who have previously received a JAK inhibitor and are ineligible for or cannot tolerate additional JAK inhibitor therapy, lost response to a JAK inhibitor, or are resistant or refractory to JAK inhibition
• MF patients who are transfusion-dependent or -independent whose disease is not being adequately controlled by ruxolitinib
• MF patients who are anemic and have not previously received a JAK inhibitor.

According to Constellation Pharmaceuticals, CPI-0610 demonstrated clinical activity in the first four patients treated on this trial, all of whom previously received a JAK inhibitor.

The researchers observed reductions in spleen volume and improvements in hemoglobin levels in patients who received monotherapy (n=2) or CPI-0610 plus ruxolitinib (n=2).

One patient treated with the combination experienced resolution of thrombocytosis and became transfusion-independent.

The company said proof-of-concept data from this trial are expected in mid-2019.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Micrograph showing myelofibrosis

The U.S. Food and Drug Administration (FDA) has granted fast track designation to CPI-0610 for the treatment of myelofibrosis (MF).

CPI-0610 is a BET inhibitor being developed by Constellation Pharmaceuticals, Inc.

The company said results from preclinical studies and translational insights from the first-in-human study of CPI-0610 led to the prioritization of CPI-0610 as a potential treatment for MF.

The company is now enrolling patients in the phase 2 portion of the phase 1/2 MANIFEST trial (NCT02158858).

In this trial, researchers are testing CPI-0610 alone or in combination with ruxolitinib in the following patient groups:

• Transfusion-dependent or -independent MF patients who have previously received a JAK inhibitor and are ineligible for or cannot tolerate additional JAK inhibitor therapy, lost response to a JAK inhibitor, or are resistant or refractory to JAK inhibition
• MF patients who are transfusion-dependent or -independent whose disease is not being adequately controlled by ruxolitinib
• MF patients who are anemic and have not previously received a JAK inhibitor.

According to Constellation Pharmaceuticals, CPI-0610 demonstrated clinical activity in the first four patients treated on this trial, all of whom previously received a JAK inhibitor.

The researchers observed reductions in spleen volume and improvements in hemoglobin levels in patients who received monotherapy (n=2) or CPI-0610 plus ruxolitinib (n=2).

One patient treated with the combination experienced resolution of thrombocytosis and became transfusion-independent.

The company said proof-of-concept data from this trial are expected in mid-2019.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

SEATTLE – Mindfulness exercises can ease stress for low-income parents and improve mental health measures in their children, results of a small pilot study presented at the American Academy of Child and Adolescent Psychiatry indicate.

The researchers credit the location of the mindfulness intervention, an early childhood developmental center, and the focus on the child rather than the parent for the success of the program. The intervention is designed to help the child, and that is the major message to the parent. “Every parent will do things to help their child, even though not every parent will do things to help themselves,” said Matthew G. Biel, MD, of Georgetown University, Washington, who presented the study at a poster session.

Mindfulness has gained traction among adults and children, but its application to parenting is new, he said. The study was open label and included 33 caregivers of children aged 0-5 years (85% female, 82% African American, 85% with household income less than $50,000/year). All subjects participated in a weekly mindfulness session lasting 60-90 minutes, which was led by an experienced instructor who had strong cultural knowledge of the local community. Sessions were conducted in a circle and included mindfulness practices and parent sharing of experiences. Focal points for mindfulness practices included breathing, body awareness, mindful movement, thoughts, emotions, and mindful listening and speaking.

The intervention was associated with statistically significant improvements in a range of measures, including sleep disturbance (effect size, 0.50; P = .005), parenting stress (ES, 0.33; P = .012), mindful discipline (ES, 0.21; P = .043), parental support (ES, 0.44; P = .007), child autonomy (ES, 032; P = .033), positive affect in parents (ES, 0.28; P = .046) and negative affect in parents (ES, 0.49; P = .028), and overall parental mental health (ES, 0.55; P = .020). “Across the board we’re seeing a positive impact,” said Dr. Biel.

The researchers are now implementing the program in another school and planning an intervention study with a waiting list control.

Satyani McPherson, a coauthor of the study and a mindfulness expert who has been teaching since the 1980s, explained that mindfulness really needs to be experienced to be understood. “You can talk about this all day, and no one gets it until they experience it. As soon as people have their mindfulness practice, they come out of it and they say, ‘Aaah, I feel so much better,’ ” she said in an interview.

The key to success lies in repetition and practice, and parents who did their mindfulness “homework” between sessions saw more benefit in the pilot study, said Ms. McPherson. The good news is that mindfulness can be incorporated into all sorts of daily activities, whether it’s showering, eating, or being stopped at a red light. It can even be used as a sort of time-out for patients. “Go into the restroom, lock the door, and observe your breath for one minute, or just one breath or three breaths. It helps you to ground yourself,” said Ms. McPherson.

Ms McPherson is an employee of Minds Incorporated. Dr. Biel receives research support from the Bainum Family Foundation, Chan-Zuckerberg Initiative, DC Health, Marriott Foundation, and self-funds his research.

SOURCE: AACAP 2018. Abstract 1.40.

SEATTLE – Mindfulness exercises can ease stress for low-income parents and improve mental health measures in their children, results of a small pilot study presented at the American Academy of Child and Adolescent Psychiatry indicate.

The researchers credit the location of the mindfulness intervention, an early childhood developmental center, and the focus on the child rather than the parent for the success of the program. The intervention is designed to help the child, and that is the major message to the parent. “Every parent will do things to help their child, even though not every parent will do things to help themselves,” said Matthew G. Biel, MD, of Georgetown University, Washington, who presented the study at a poster session.

Mindfulness has gained traction among adults and children, but its application to parenting is new, he said. The study was open label and included 33 caregivers of children aged 0-5 years (85% female, 82% African American, 85% with household income less than $50,000/year). All subjects participated in a weekly mindfulness session lasting 60-90 minutes, which was led by an experienced instructor who had strong cultural knowledge of the local community. Sessions were conducted in a circle and included mindfulness practices and parent sharing of experiences. Focal points for mindfulness practices included breathing, body awareness, mindful movement, thoughts, emotions, and mindful listening and speaking.

The intervention was associated with statistically significant improvements in a range of measures, including sleep disturbance (effect size, 0.50; P = .005), parenting stress (ES, 0.33; P = .012), mindful discipline (ES, 0.21; P = .043), parental support (ES, 0.44; P = .007), child autonomy (ES, 032; P = .033), positive affect in parents (ES, 0.28; P = .046) and negative affect in parents (ES, 0.49; P = .028), and overall parental mental health (ES, 0.55; P = .020). “Across the board we’re seeing a positive impact,” said Dr. Biel.

The researchers are now implementing the program in another school and planning an intervention study with a waiting list control.

Satyani McPherson, a coauthor of the study and a mindfulness expert who has been teaching since the 1980s, explained that mindfulness really needs to be experienced to be understood. “You can talk about this all day, and no one gets it until they experience it. As soon as people have their mindfulness practice, they come out of it and they say, ‘Aaah, I feel so much better,’ ” she said in an interview.

The key to success lies in repetition and practice, and parents who did their mindfulness “homework” between sessions saw more benefit in the pilot study, said Ms. McPherson. The good news is that mindfulness can be incorporated into all sorts of daily activities, whether it’s showering, eating, or being stopped at a red light. It can even be used as a sort of time-out for patients. “Go into the restroom, lock the door, and observe your breath for one minute, or just one breath or three breaths. It helps you to ground yourself,” said Ms. McPherson.

Ms McPherson is an employee of Minds Incorporated. Dr. Biel receives research support from the Bainum Family Foundation, Chan-Zuckerberg Initiative, DC Health, Marriott Foundation, and self-funds his research.

SOURCE: AACAP 2018. Abstract 1.40.

SEATTLE – Mindfulness exercises can ease stress for low-income parents and improve mental health measures in their children, results of a small pilot study presented at the American Academy of Child and Adolescent Psychiatry indicate.

The researchers credit the location of the mindfulness intervention, an early childhood developmental center, and the focus on the child rather than the parent for the success of the program. The intervention is designed to help the child, and that is the major message to the parent. “Every parent will do things to help their child, even though not every parent will do things to help themselves,” said Matthew G. Biel, MD, of Georgetown University, Washington, who presented the study at a poster session.

Mindfulness has gained traction among adults and children, but its application to parenting is new, he said. The study was open label and included 33 caregivers of children aged 0-5 years (85% female, 82% African American, 85% with household income less than $50,000/year). All subjects participated in a weekly mindfulness session lasting 60-90 minutes, which was led by an experienced instructor who had strong cultural knowledge of the local community. Sessions were conducted in a circle and included mindfulness practices and parent sharing of experiences. Focal points for mindfulness practices included breathing, body awareness, mindful movement, thoughts, emotions, and mindful listening and speaking.

The intervention was associated with statistically significant improvements in a range of measures, including sleep disturbance (effect size, 0.50; P = .005), parenting stress (ES, 0.33; P = .012), mindful discipline (ES, 0.21; P = .043), parental support (ES, 0.44; P = .007), child autonomy (ES, 032; P = .033), positive affect in parents (ES, 0.28; P = .046) and negative affect in parents (ES, 0.49; P = .028), and overall parental mental health (ES, 0.55; P = .020). “Across the board we’re seeing a positive impact,” said Dr. Biel.

The researchers are now implementing the program in another school and planning an intervention study with a waiting list control.

Satyani McPherson, a coauthor of the study and a mindfulness expert who has been teaching since the 1980s, explained that mindfulness really needs to be experienced to be understood. “You can talk about this all day, and no one gets it until they experience it. As soon as people have their mindfulness practice, they come out of it and they say, ‘Aaah, I feel so much better,’ ” she said in an interview.

The key to success lies in repetition and practice, and parents who did their mindfulness “homework” between sessions saw more benefit in the pilot study, said Ms. McPherson. The good news is that mindfulness can be incorporated into all sorts of daily activities, whether it’s showering, eating, or being stopped at a red light. It can even be used as a sort of time-out for patients. “Go into the restroom, lock the door, and observe your breath for one minute, or just one breath or three breaths. It helps you to ground yourself,” said Ms. McPherson.

Ms McPherson is an employee of Minds Incorporated. Dr. Biel receives research support from the Bainum Family Foundation, Chan-Zuckerberg Initiative, DC Health, Marriott Foundation, and self-funds his research.

SOURCE: AACAP 2018. Abstract 1.40.

Researchers did not find any difference in number of self-reported premenstrual syndrome (PMS) symptoms between migraineurs with and without menstrual migraine (MM), according to a recent study. A total of 237 women from the general population who self-reported migraine in at least 50% of their menstrual periods were invited to a clinical interview and diagnosed by a neurologist. All women were asked to complete a self-administered form containing 11 questions about PMS symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS). They found:

• 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n=61) or because they did not fulfill the ICHD-criteria for migraine (n=6).
• Among the remaining 126 migraineurs, 78 had MM and 48 had non-menstrually related migraine.
• PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs 5.9).
• Women with MM reported more migraine days/month, longer lasting migraine attacks, and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Vetvik KG, MacGregor EA, Lundqyist C, Russell MB. Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine. [Published online ahead of print October 17, 2018]. J Headache Pain. doi:10.1186/s10194-018-0931-6.

Researchers did not find any difference in number of self-reported premenstrual syndrome (PMS) symptoms between migraineurs with and without menstrual migraine (MM), according to a recent study. A total of 237 women from the general population who self-reported migraine in at least 50% of their menstrual periods were invited to a clinical interview and diagnosed by a neurologist. All women were asked to complete a self-administered form containing 11 questions about PMS symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS). They found:

• 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n=61) or because they did not fulfill the ICHD-criteria for migraine (n=6).
• Among the remaining 126 migraineurs, 78 had MM and 48 had non-menstrually related migraine.
• PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs 5.9).
• Women with MM reported more migraine days/month, longer lasting migraine attacks, and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Vetvik KG, MacGregor EA, Lundqyist C, Russell MB. Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine. [Published online ahead of print October 17, 2018]. J Headache Pain. doi:10.1186/s10194-018-0931-6.

Researchers did not find any difference in number of self-reported premenstrual syndrome (PMS) symptoms between migraineurs with and without menstrual migraine (MM), according to a recent study. A total of 237 women from the general population who self-reported migraine in at least 50% of their menstrual periods were invited to a clinical interview and diagnosed by a neurologist. All women were asked to complete a self-administered form containing 11 questions about PMS symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS). They found:

• 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n=61) or because they did not fulfill the ICHD-criteria for migraine (n=6).
• Among the remaining 126 migraineurs, 78 had MM and 48 had non-menstrually related migraine.
• PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs 5.9).
• Women with MM reported more migraine days/month, longer lasting migraine attacks, and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Vetvik KG, MacGregor EA, Lundqyist C, Russell MB. Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine. [Published online ahead of print October 17, 2018]. J Headache Pain. doi:10.1186/s10194-018-0931-6.

Typical aura without headache, a rare subtype of migraine, occurs exclusively in 4% patients with migraine, and may take place at some point in 38% of patients with migraine with aura, according to recent study. Furthermore, typical aura without headache, also known as migraine aura without headache or acephalgic migraine, commonly presents with visual aura without headache, brainstem aura without headache, and can also develop later in life, known as late-onset migraine accompaniment. Its pathophysiology is suggested to be similar to classic migraines, with cortical spreading depression leading to aura formation but without an associated headache. Presently, no clinical trials have been performed to evaluate treatment options, but case reports suggest that most patients will respond to the traditional treatments for migraine with aura.

Shah DR, Dilwali S, Friedman DI. Migraine aura without headache. Curr Pain Headache Rep. 2018;22:77. doi:10.1007/s11916-018-0725-1.

Typical aura without headache, a rare subtype of migraine, occurs exclusively in 4% patients with migraine, and may take place at some point in 38% of patients with migraine with aura, according to recent study. Furthermore, typical aura without headache, also known as migraine aura without headache or acephalgic migraine, commonly presents with visual aura without headache, brainstem aura without headache, and can also develop later in life, known as late-onset migraine accompaniment. Its pathophysiology is suggested to be similar to classic migraines, with cortical spreading depression leading to aura formation but without an associated headache. Presently, no clinical trials have been performed to evaluate treatment options, but case reports suggest that most patients will respond to the traditional treatments for migraine with aura.

Shah DR, Dilwali S, Friedman DI. Migraine aura without headache. Curr Pain Headache Rep. 2018;22:77. doi:10.1007/s11916-018-0725-1.

Typical aura without headache, a rare subtype of migraine, occurs exclusively in 4% patients with migraine, and may take place at some point in 38% of patients with migraine with aura, according to recent study. Furthermore, typical aura without headache, also known as migraine aura without headache or acephalgic migraine, commonly presents with visual aura without headache, brainstem aura without headache, and can also develop later in life, known as late-onset migraine accompaniment. Its pathophysiology is suggested to be similar to classic migraines, with cortical spreading depression leading to aura formation but without an associated headache. Presently, no clinical trials have been performed to evaluate treatment options, but case reports suggest that most patients will respond to the traditional treatments for migraine with aura.

Shah DR, Dilwali S, Friedman DI. Migraine aura without headache. Curr Pain Headache Rep. 2018;22:77. doi:10.1007/s11916-018-0725-1.