And remember: you must never, under any circumstances, despair. To hope and to act, these are our duties in misfortune.

—Boris Pasternak, Doctor Zhivago

This editorial is being written on Veterans Day. Likely you will read it when the stores and streets are lined with holiday decorations. Thanksgiving will have come and gone. All these celebrations have the common themes of giving and gratitude, and among the many requests clamoring for your attention at this season are care package collections for active-duty service members and donations for disadvantaged veterans. These efforts are well intentioned on the part of givers and appreciated on the part of those who receive them. Yet these themes remind me of the hackneyed saying we likely have all heard, and many of us have said: Thank you for your service.

Many of you may recall the controversy that emerged surrounding this seemingly innocuous cliché. It has had an Internet resurgence on this day set out to honor those who wore or are in uniform.¹ For those who don’t remember the phenomenon, I will briefly summarize. A journalist was interviewing a combat veteran from Afghanistan on a different subject but knowing he had been in the military and the reporter thinking he was being kind and respectful, like so many of us, thanked him for his service. The astute journalist could tell from the expression on the veteran’s face that the comment had touched a wound he never expected to open. But he cared enough to try and understand how the veteran heard these words from out of the depths of his memories of war.

The emotions that emerged from the interview and the online blogs and comments that followed reflect the toll that war takes: anger, anguish, alienation, which these “have a nice day” words seem to evoke, even though they are never meant to create distance, dismissal, or dishonor. This interaction was a painful one for the veteran, and even for the journalist, and created what psychologists call cognitive dissonance, “a condition of conflict or anxiety resulting from inconsistency between belief and action.”²

The reason those 5 words strike a raw nerve in some—but by no means all—who were or are in the armed forces is that those to whom they are spoken know in a deep and personal way, that we who say them usually do not know what we are talking about. I can see this reaction when I watch several of my VA colleagues who actually are combat veterans say the words but from a different theory of mind, a theory of mind they share. Theory of mind is another psychological concept that is at the core of interpersonal and communication skills, the ability to see and feel the world as another person sees it. When someone who has never fought or even served says “thank you for your service,” some veterans feel that their individual experience of combat or even of being in the military is being expressed inauthentically, even perhaps insincerely.

“To these vets, thanking soldiers for their service symbolizes the ease of sending a volunteer army to wage war at great distance—physically, spiritually, economically,” journalist Matt Richtel writes. “It raises questions of the meaning of patriotism, shared purpose and, pointedly, what you’re supposed to say to those who put their lives on the line and are uncomfortable about being thanked for it.”²

My father, a World War II combat veteran and career army physician, told me when I was young that there were 3 experiences that could never be understood unless you lived them: pregnancy, medical school, and combat. I’m not sure why or how he chose these although I am sure they were not original, but having gone through the second, I believe it was because these events are of such personal intensity, such immediate contact with the human condition in all its suffering and resilience that they cannot be faithfully replicated in any in vitro simulation but only in vivo.

Which brings me to the title of the column. How can we say thank you to our friends and family members, our coworkers, and our patients who went to war and returned, who enlisted ready to go into combat even if the fates did not send them? Reading the comments of these men and women in response to the superficial phrase with which we habitually acknowledge their sacrifice leaves me wondering what to say to express our obligation to those who struggled through foreign tribulations while we remained safe at home. Their reflections offer some surprising suggestions that seem prophetic as we as a country process the results of the recent election with grief, triumph, or indifference.

We can say thank you through voting, donations, or advocacy as long as we act to promote the most fundamental good for humanity. We say thank you when we act to help a veteran to live a decent and rewarding life, to have a safe place to live, to grow through education, to share life with companions, and to find a job or another way to contribute to society. Actions to improve the living conditions of veterans now and a better future for those who leave the ranks are seeds of gratitude that come to fruition long after the empty phrases are forgotten.

We say thank you when we think and question long and hard until it hurts, until we too experience cognitive dissonance, until our theory of mind is stretched beyond its comfortable boundaries about the purpose of war in general and the justification for any particular conflict in which our government contemplates sending the young and brave to fight and die. Acting and thinking honor sacrifice as words never can.

And remember: you must never, under any circumstances, despair. To hope and to act, these are our duties in misfortune.

—Boris Pasternak, Doctor Zhivago

This editorial is being written on Veterans Day. Likely you will read it when the stores and streets are lined with holiday decorations. Thanksgiving will have come and gone. All these celebrations have the common themes of giving and gratitude, and among the many requests clamoring for your attention at this season are care package collections for active-duty service members and donations for disadvantaged veterans. These efforts are well intentioned on the part of givers and appreciated on the part of those who receive them. Yet these themes remind me of the hackneyed saying we likely have all heard, and many of us have said: Thank you for your service.

Many of you may recall the controversy that emerged surrounding this seemingly innocuous cliché. It has had an Internet resurgence on this day set out to honor those who wore or are in uniform.¹ For those who don’t remember the phenomenon, I will briefly summarize. A journalist was interviewing a combat veteran from Afghanistan on a different subject but knowing he had been in the military and the reporter thinking he was being kind and respectful, like so many of us, thanked him for his service. The astute journalist could tell from the expression on the veteran’s face that the comment had touched a wound he never expected to open. But he cared enough to try and understand how the veteran heard these words from out of the depths of his memories of war.

The emotions that emerged from the interview and the online blogs and comments that followed reflect the toll that war takes: anger, anguish, alienation, which these “have a nice day” words seem to evoke, even though they are never meant to create distance, dismissal, or dishonor. This interaction was a painful one for the veteran, and even for the journalist, and created what psychologists call cognitive dissonance, “a condition of conflict or anxiety resulting from inconsistency between belief and action.”²

The reason those 5 words strike a raw nerve in some—but by no means all—who were or are in the armed forces is that those to whom they are spoken know in a deep and personal way, that we who say them usually do not know what we are talking about. I can see this reaction when I watch several of my VA colleagues who actually are combat veterans say the words but from a different theory of mind, a theory of mind they share. Theory of mind is another psychological concept that is at the core of interpersonal and communication skills, the ability to see and feel the world as another person sees it. When someone who has never fought or even served says “thank you for your service,” some veterans feel that their individual experience of combat or even of being in the military is being expressed inauthentically, even perhaps insincerely.

“To these vets, thanking soldiers for their service symbolizes the ease of sending a volunteer army to wage war at great distance—physically, spiritually, economically,” journalist Matt Richtel writes. “It raises questions of the meaning of patriotism, shared purpose and, pointedly, what you’re supposed to say to those who put their lives on the line and are uncomfortable about being thanked for it.”²

My father, a World War II combat veteran and career army physician, told me when I was young that there were 3 experiences that could never be understood unless you lived them: pregnancy, medical school, and combat. I’m not sure why or how he chose these although I am sure they were not original, but having gone through the second, I believe it was because these events are of such personal intensity, such immediate contact with the human condition in all its suffering and resilience that they cannot be faithfully replicated in any in vitro simulation but only in vivo.

Which brings me to the title of the column. How can we say thank you to our friends and family members, our coworkers, and our patients who went to war and returned, who enlisted ready to go into combat even if the fates did not send them? Reading the comments of these men and women in response to the superficial phrase with which we habitually acknowledge their sacrifice leaves me wondering what to say to express our obligation to those who struggled through foreign tribulations while we remained safe at home. Their reflections offer some surprising suggestions that seem prophetic as we as a country process the results of the recent election with grief, triumph, or indifference.

We can say thank you through voting, donations, or advocacy as long as we act to promote the most fundamental good for humanity. We say thank you when we act to help a veteran to live a decent and rewarding life, to have a safe place to live, to grow through education, to share life with companions, and to find a job or another way to contribute to society. Actions to improve the living conditions of veterans now and a better future for those who leave the ranks are seeds of gratitude that come to fruition long after the empty phrases are forgotten.

We say thank you when we think and question long and hard until it hurts, until we too experience cognitive dissonance, until our theory of mind is stretched beyond its comfortable boundaries about the purpose of war in general and the justification for any particular conflict in which our government contemplates sending the young and brave to fight and die. Acting and thinking honor sacrifice as words never can.

And remember: you must never, under any circumstances, despair. To hope and to act, these are our duties in misfortune.

—Boris Pasternak, Doctor Zhivago

This editorial is being written on Veterans Day. Likely you will read it when the stores and streets are lined with holiday decorations. Thanksgiving will have come and gone. All these celebrations have the common themes of giving and gratitude, and among the many requests clamoring for your attention at this season are care package collections for active-duty service members and donations for disadvantaged veterans. These efforts are well intentioned on the part of givers and appreciated on the part of those who receive them. Yet these themes remind me of the hackneyed saying we likely have all heard, and many of us have said: Thank you for your service.

Many of you may recall the controversy that emerged surrounding this seemingly innocuous cliché. It has had an Internet resurgence on this day set out to honor those who wore or are in uniform.¹ For those who don’t remember the phenomenon, I will briefly summarize. A journalist was interviewing a combat veteran from Afghanistan on a different subject but knowing he had been in the military and the reporter thinking he was being kind and respectful, like so many of us, thanked him for his service. The astute journalist could tell from the expression on the veteran’s face that the comment had touched a wound he never expected to open. But he cared enough to try and understand how the veteran heard these words from out of the depths of his memories of war.

The emotions that emerged from the interview and the online blogs and comments that followed reflect the toll that war takes: anger, anguish, alienation, which these “have a nice day” words seem to evoke, even though they are never meant to create distance, dismissal, or dishonor. This interaction was a painful one for the veteran, and even for the journalist, and created what psychologists call cognitive dissonance, “a condition of conflict or anxiety resulting from inconsistency between belief and action.”²

The reason those 5 words strike a raw nerve in some—but by no means all—who were or are in the armed forces is that those to whom they are spoken know in a deep and personal way, that we who say them usually do not know what we are talking about. I can see this reaction when I watch several of my VA colleagues who actually are combat veterans say the words but from a different theory of mind, a theory of mind they share. Theory of mind is another psychological concept that is at the core of interpersonal and communication skills, the ability to see and feel the world as another person sees it. When someone who has never fought or even served says “thank you for your service,” some veterans feel that their individual experience of combat or even of being in the military is being expressed inauthentically, even perhaps insincerely.

“To these vets, thanking soldiers for their service symbolizes the ease of sending a volunteer army to wage war at great distance—physically, spiritually, economically,” journalist Matt Richtel writes. “It raises questions of the meaning of patriotism, shared purpose and, pointedly, what you’re supposed to say to those who put their lives on the line and are uncomfortable about being thanked for it.”²

My father, a World War II combat veteran and career army physician, told me when I was young that there were 3 experiences that could never be understood unless you lived them: pregnancy, medical school, and combat. I’m not sure why or how he chose these although I am sure they were not original, but having gone through the second, I believe it was because these events are of such personal intensity, such immediate contact with the human condition in all its suffering and resilience that they cannot be faithfully replicated in any in vitro simulation but only in vivo.

Which brings me to the title of the column. How can we say thank you to our friends and family members, our coworkers, and our patients who went to war and returned, who enlisted ready to go into combat even if the fates did not send them? Reading the comments of these men and women in response to the superficial phrase with which we habitually acknowledge their sacrifice leaves me wondering what to say to express our obligation to those who struggled through foreign tribulations while we remained safe at home. Their reflections offer some surprising suggestions that seem prophetic as we as a country process the results of the recent election with grief, triumph, or indifference.

We can say thank you through voting, donations, or advocacy as long as we act to promote the most fundamental good for humanity. We say thank you when we act to help a veteran to live a decent and rewarding life, to have a safe place to live, to grow through education, to share life with companions, and to find a job or another way to contribute to society. Actions to improve the living conditions of veterans now and a better future for those who leave the ranks are seeds of gratitude that come to fruition long after the empty phrases are forgotten.

We say thank you when we think and question long and hard until it hurts, until we too experience cognitive dissonance, until our theory of mind is stretched beyond its comfortable boundaries about the purpose of war in general and the justification for any particular conflict in which our government contemplates sending the young and brave to fight and die. Acting and thinking honor sacrifice as words never can.

Click here to access the December 2016 Digital Edition

Table of Contents

• How Can We Say Thank You?
• How Well Does the Braden Nutrition Subscale Agree With the VA Nutrition Classification Scheme Related to Pressure Ulcer Risk?
• Proton Pump Inhibitor-Associated Hypomagnesemia
• Simulation Training, Coaching, and Cue Cards Improve Delirium Care
• Memory Skills Classes for Older Veterans With a History of Posttraumatic Stress Disorder
• Neurosurgical Subspecialty Bedside Nursing Guide Improves Confidence
• A Primary Care Approach to Managing Chronic Noncancer Pain
• "Where’s the Music?" Using Music Therapy for Pain Management

Click here to access the December 2016 Digital Edition

Table of Contents

• How Can We Say Thank You?
• How Well Does the Braden Nutrition Subscale Agree With the VA Nutrition Classification Scheme Related to Pressure Ulcer Risk?
• Proton Pump Inhibitor-Associated Hypomagnesemia
• Simulation Training, Coaching, and Cue Cards Improve Delirium Care
• Memory Skills Classes for Older Veterans With a History of Posttraumatic Stress Disorder
• Neurosurgical Subspecialty Bedside Nursing Guide Improves Confidence
• A Primary Care Approach to Managing Chronic Noncancer Pain
• "Where’s the Music?" Using Music Therapy for Pain Management

Click here to access the December 2016 Digital Edition

Table of Contents

• How Can We Say Thank You?
• How Well Does the Braden Nutrition Subscale Agree With the VA Nutrition Classification Scheme Related to Pressure Ulcer Risk?
• Proton Pump Inhibitor-Associated Hypomagnesemia
• Simulation Training, Coaching, and Cue Cards Improve Delirium Care
• Memory Skills Classes for Older Veterans With a History of Posttraumatic Stress Disorder
• Neurosurgical Subspecialty Bedside Nursing Guide Improves Confidence
• A Primary Care Approach to Managing Chronic Noncancer Pain
• "Where’s the Music?" Using Music Therapy for Pain Management

Not all cancers are the same, and quality of life (QOL) for cancer survivors is not the same across the board. Researchers from Fudan University in Shanghai, China, say the effects of exercise for cancer survivors are different, too.

The researchers surveyed 3,392 cancer survivors (colorectal, lung, ovarian, cervical, liver, and endometrial). They asked the patients about the type of physical activity (PA) they engaged in (eg, vigorous walking, table tennis, tai chi) for at least 30 minutes once a week in the previous month. They also asked about frequency (1 – 4 times a week and 5 or more times a week). They used a 27-item self-reporting instrument to measure QOL, with questions on functional status, symptoms, and emotional and social well-being.

Related: Exercise Lowers Risk of Some Cancers

Liver cancer survivors had the poorest QOL in several areas, including the highest level of appetite loss, worst emotional well-being, and worst financial difficulties. Lung cancer survivors reported worse physical functioning than did gynecologic or colorectal cancer survivors, as well as higher scores for dyspnea. Colorectal cancer survivors had the second highest scores on appetite loss and the most serious diarrhea.

However, survivors of all cancer types who engaged in PA reported statistically significant higher scores in physical functioning than did their counterparts. Survivors of lung, gynecologic, and colorectal cancer reported significantly better cognitive functioning. The association was not observed among liver cancer survivors.

Physically active survivors also generally reported lower symptom levels—although only insomnia was significantly lower (among liver cancer survivors). Physically active survivors did not show statistically significant improvements in constipation or diarrhea.

Related: Improving the Quality of Life and Care for Cancer Survivors

Physically active survivors of lung, gynecologic, and colorectal cancer received significantly higher scores on well-being scales. The relationship between PA and QOL was not statistically significant among liver cancer survivors.

The researchers did not observe associations between increased frequency of PA and physical functioning or physical well-being among gynecologic or liver cancer survivors. In fact, gynecologic cancer survivors with more frequent PA reported poorer QOL in role functioning, social functioning, and global health status, as well as lower scores on many symptom scales. The researchers found similar results among colorectal and liver cancer survivors; they say this may be because higher PA frequency is related to poorer QOL conditions for some measures.

Related: The Impact of Obesity on the Recovery of Patients With Cancer

Finally, the researchers were not able to define a statistically significant association between PA frequency and QOL. Based on their findings, they “cautiously advocate” for not “strongly” suggesting a higher frequency of PA to gynecologic, colorectal, or liver cancer survivors.

Source:
Tang F, Wang J, Tang Z, Kang M, Deng Q, Yu J. PLoS ONE. 2016;11(11):e0164971.

Not all cancers are the same, and quality of life (QOL) for cancer survivors is not the same across the board. Researchers from Fudan University in Shanghai, China, say the effects of exercise for cancer survivors are different, too.

The researchers surveyed 3,392 cancer survivors (colorectal, lung, ovarian, cervical, liver, and endometrial). They asked the patients about the type of physical activity (PA) they engaged in (eg, vigorous walking, table tennis, tai chi) for at least 30 minutes once a week in the previous month. They also asked about frequency (1 – 4 times a week and 5 or more times a week). They used a 27-item self-reporting instrument to measure QOL, with questions on functional status, symptoms, and emotional and social well-being.

Related: Exercise Lowers Risk of Some Cancers

Liver cancer survivors had the poorest QOL in several areas, including the highest level of appetite loss, worst emotional well-being, and worst financial difficulties. Lung cancer survivors reported worse physical functioning than did gynecologic or colorectal cancer survivors, as well as higher scores for dyspnea. Colorectal cancer survivors had the second highest scores on appetite loss and the most serious diarrhea.

However, survivors of all cancer types who engaged in PA reported statistically significant higher scores in physical functioning than did their counterparts. Survivors of lung, gynecologic, and colorectal cancer reported significantly better cognitive functioning. The association was not observed among liver cancer survivors.

Physically active survivors also generally reported lower symptom levels—although only insomnia was significantly lower (among liver cancer survivors). Physically active survivors did not show statistically significant improvements in constipation or diarrhea.

Related: Improving the Quality of Life and Care for Cancer Survivors

Physically active survivors of lung, gynecologic, and colorectal cancer received significantly higher scores on well-being scales. The relationship between PA and QOL was not statistically significant among liver cancer survivors.

The researchers did not observe associations between increased frequency of PA and physical functioning or physical well-being among gynecologic or liver cancer survivors. In fact, gynecologic cancer survivors with more frequent PA reported poorer QOL in role functioning, social functioning, and global health status, as well as lower scores on many symptom scales. The researchers found similar results among colorectal and liver cancer survivors; they say this may be because higher PA frequency is related to poorer QOL conditions for some measures.

Related: The Impact of Obesity on the Recovery of Patients With Cancer

Finally, the researchers were not able to define a statistically significant association between PA frequency and QOL. Based on their findings, they “cautiously advocate” for not “strongly” suggesting a higher frequency of PA to gynecologic, colorectal, or liver cancer survivors.

Source:
Tang F, Wang J, Tang Z, Kang M, Deng Q, Yu J. PLoS ONE. 2016;11(11):e0164971.

Not all cancers are the same, and quality of life (QOL) for cancer survivors is not the same across the board. Researchers from Fudan University in Shanghai, China, say the effects of exercise for cancer survivors are different, too.

The researchers surveyed 3,392 cancer survivors (colorectal, lung, ovarian, cervical, liver, and endometrial). They asked the patients about the type of physical activity (PA) they engaged in (eg, vigorous walking, table tennis, tai chi) for at least 30 minutes once a week in the previous month. They also asked about frequency (1 – 4 times a week and 5 or more times a week). They used a 27-item self-reporting instrument to measure QOL, with questions on functional status, symptoms, and emotional and social well-being.

Related: Exercise Lowers Risk of Some Cancers

Liver cancer survivors had the poorest QOL in several areas, including the highest level of appetite loss, worst emotional well-being, and worst financial difficulties. Lung cancer survivors reported worse physical functioning than did gynecologic or colorectal cancer survivors, as well as higher scores for dyspnea. Colorectal cancer survivors had the second highest scores on appetite loss and the most serious diarrhea.

However, survivors of all cancer types who engaged in PA reported statistically significant higher scores in physical functioning than did their counterparts. Survivors of lung, gynecologic, and colorectal cancer reported significantly better cognitive functioning. The association was not observed among liver cancer survivors.

Physically active survivors also generally reported lower symptom levels—although only insomnia was significantly lower (among liver cancer survivors). Physically active survivors did not show statistically significant improvements in constipation or diarrhea.

Related: Improving the Quality of Life and Care for Cancer Survivors

Physically active survivors of lung, gynecologic, and colorectal cancer received significantly higher scores on well-being scales. The relationship between PA and QOL was not statistically significant among liver cancer survivors.

The researchers did not observe associations between increased frequency of PA and physical functioning or physical well-being among gynecologic or liver cancer survivors. In fact, gynecologic cancer survivors with more frequent PA reported poorer QOL in role functioning, social functioning, and global health status, as well as lower scores on many symptom scales. The researchers found similar results among colorectal and liver cancer survivors; they say this may be because higher PA frequency is related to poorer QOL conditions for some measures.

Related: The Impact of Obesity on the Recovery of Patients With Cancer

Finally, the researchers were not able to define a statistically significant association between PA frequency and QOL. Based on their findings, they “cautiously advocate” for not “strongly” suggesting a higher frequency of PA to gynecologic, colorectal, or liver cancer survivors.

Source:
Tang F, Wang J, Tang Z, Kang M, Deng Q, Yu J. PLoS ONE. 2016;11(11):e0164971.

Lab mice

Photo by Aaron Logan

Researchers have created a patch designed to monitor a patient’s blood and release heparin as needed to prevent thrombosis.

In mice, the patch successfully released heparin into the bloodstream and proved more effective at preventing thrombosis than an injection of heparin.

Zhen Gu, PhD, of the University of North Carolina at Chapel Hill, and his colleagues developed the patch and described it in Advanced Materials.

“Our goal was to generate a patch that can monitor a patient’s blood and release additional drugs when necessary; effectively, a self-regulating system,” Dr Gu said.

The patch incorporates microneedles made of a polymer that consists of hyaluronic acid (HA) and the drug heparin. The polymer has been modified to be responsive to thrombin.

When elevated levels of thrombin enzymes in the bloodstream come into contact with the microneedle, the enzymes break the amino acid chains that bind the heparin to the HA, releasing the heparin into the bloodstream.

“The more thrombin there is in the bloodstream, the more heparin is needed to reduce clotting,” said study author Yuqi Zhang, a PhD student in Dr Gu’s lab. “So we created a disposable patch in which the more thrombin there is in the bloodstream, the more heparin is released.”

“We will further enhance the loading amount of drug in the patch,” said study author Jicheng Yu, a PhD student in Dr Gu’s lab.

“The amount of heparin in a patch can be tailored to a patient’s specific needs and replaced daily, or less often, as needed. But the amount of heparin being released into the patient at any given moment will be determined by the thrombin levels in the patient’s blood.”

Experiments in mice

The researchers tested the patch in a mouse model of thrombosis. The mice were injected with large doses of thrombin (1000 U kg^-1) to induce an acute thromboembolism, which can lead to death in about 92% of mice.

The mice were then randomized into 5 different treatment groups:

• Intravenous heparin injection
• Empty HA microneedle patch
• HA microneedle patch encapsulating free heparin
• Thrombin-responsive HA-heparin microneedle patch
• Non-responsive HA-heparin microneedle patch (heparin dose: 200 U kg⁻¹).

The mice that received heparin via injection were treated before thrombosis induction. The microneedle patches were applied to the dorsum skin of the mice 10 minutes before the challenge.

All of the mice with the HA microneedle patch or the non-responsive HA-heparin microneedle patch died within 15 minutes of the thrombin injection.

All of the mice that received the heparin injection, heparin microneedle patch, or the thrombin-responsive HA-heparin microneedle patch survived the 15 minutes.

In a second experiment, mice received a thrombin injection 6 hours after treatment, and treatment consisted of:

• Heparin injection
• HA microneedle patch encapsulating free heparin
• Thrombin-responsive HA-heparin microneedle patch.

Fifteen minutes after the thrombin injection, death had occurred in 80% or more of the mice that received the heparin injection and the mice treated with the heparin microneedle patch.

But all of the mice treated with the thrombin-responsive HA-heparin microneedle patch survived.

The researchers also noted that staining of lung sections revealed the “superior anticoagulant capacity” of the thrombin-responsive HA-heparin microneedle patch.

The team observed “insignificant differences” in the lungs of healthy mice and mice treated with the thrombin-responsive HA-heparin microneedle patch.

However, mice that received a heparin injection or treatment with the heparin microneedle patch had intravascular and interstitial hemorrhage, blocked blood vessels, and atelectasis.

“We’re excited about the possibility of using a closed-loop, self-regulating smart patch to help treat a condition that affects thousands of people every year, while hopefully also driving down treatment costs,” Dr Gu said. “This paper represents a good first step, and we’re now looking for funding to perform additional preclinical testing.”

Lab mice

Photo by Aaron Logan

Researchers have created a patch designed to monitor a patient’s blood and release heparin as needed to prevent thrombosis.

In mice, the patch successfully released heparin into the bloodstream and proved more effective at preventing thrombosis than an injection of heparin.

Zhen Gu, PhD, of the University of North Carolina at Chapel Hill, and his colleagues developed the patch and described it in Advanced Materials.

“Our goal was to generate a patch that can monitor a patient’s blood and release additional drugs when necessary; effectively, a self-regulating system,” Dr Gu said.

The patch incorporates microneedles made of a polymer that consists of hyaluronic acid (HA) and the drug heparin. The polymer has been modified to be responsive to thrombin.

When elevated levels of thrombin enzymes in the bloodstream come into contact with the microneedle, the enzymes break the amino acid chains that bind the heparin to the HA, releasing the heparin into the bloodstream.

“The more thrombin there is in the bloodstream, the more heparin is needed to reduce clotting,” said study author Yuqi Zhang, a PhD student in Dr Gu’s lab. “So we created a disposable patch in which the more thrombin there is in the bloodstream, the more heparin is released.”

“We will further enhance the loading amount of drug in the patch,” said study author Jicheng Yu, a PhD student in Dr Gu’s lab.

“The amount of heparin in a patch can be tailored to a patient’s specific needs and replaced daily, or less often, as needed. But the amount of heparin being released into the patient at any given moment will be determined by the thrombin levels in the patient’s blood.”

Experiments in mice

The researchers tested the patch in a mouse model of thrombosis. The mice were injected with large doses of thrombin (1000 U kg^-1) to induce an acute thromboembolism, which can lead to death in about 92% of mice.

The mice were then randomized into 5 different treatment groups:

• Intravenous heparin injection
• Empty HA microneedle patch
• HA microneedle patch encapsulating free heparin
• Thrombin-responsive HA-heparin microneedle patch
• Non-responsive HA-heparin microneedle patch (heparin dose: 200 U kg⁻¹).

The mice that received heparin via injection were treated before thrombosis induction. The microneedle patches were applied to the dorsum skin of the mice 10 minutes before the challenge.

All of the mice with the HA microneedle patch or the non-responsive HA-heparin microneedle patch died within 15 minutes of the thrombin injection.

All of the mice that received the heparin injection, heparin microneedle patch, or the thrombin-responsive HA-heparin microneedle patch survived the 15 minutes.

In a second experiment, mice received a thrombin injection 6 hours after treatment, and treatment consisted of:

• Heparin injection
• HA microneedle patch encapsulating free heparin
• Thrombin-responsive HA-heparin microneedle patch.

Fifteen minutes after the thrombin injection, death had occurred in 80% or more of the mice that received the heparin injection and the mice treated with the heparin microneedle patch.

But all of the mice treated with the thrombin-responsive HA-heparin microneedle patch survived.

The researchers also noted that staining of lung sections revealed the “superior anticoagulant capacity” of the thrombin-responsive HA-heparin microneedle patch.

The team observed “insignificant differences” in the lungs of healthy mice and mice treated with the thrombin-responsive HA-heparin microneedle patch.

However, mice that received a heparin injection or treatment with the heparin microneedle patch had intravascular and interstitial hemorrhage, blocked blood vessels, and atelectasis.

“We’re excited about the possibility of using a closed-loop, self-regulating smart patch to help treat a condition that affects thousands of people every year, while hopefully also driving down treatment costs,” Dr Gu said. “This paper represents a good first step, and we’re now looking for funding to perform additional preclinical testing.”

Lab mice

Photo by Aaron Logan

Researchers have created a patch designed to monitor a patient’s blood and release heparin as needed to prevent thrombosis.

In mice, the patch successfully released heparin into the bloodstream and proved more effective at preventing thrombosis than an injection of heparin.

Zhen Gu, PhD, of the University of North Carolina at Chapel Hill, and his colleagues developed the patch and described it in Advanced Materials.

“Our goal was to generate a patch that can monitor a patient’s blood and release additional drugs when necessary; effectively, a self-regulating system,” Dr Gu said.

The patch incorporates microneedles made of a polymer that consists of hyaluronic acid (HA) and the drug heparin. The polymer has been modified to be responsive to thrombin.

When elevated levels of thrombin enzymes in the bloodstream come into contact with the microneedle, the enzymes break the amino acid chains that bind the heparin to the HA, releasing the heparin into the bloodstream.

“The more thrombin there is in the bloodstream, the more heparin is needed to reduce clotting,” said study author Yuqi Zhang, a PhD student in Dr Gu’s lab. “So we created a disposable patch in which the more thrombin there is in the bloodstream, the more heparin is released.”

“We will further enhance the loading amount of drug in the patch,” said study author Jicheng Yu, a PhD student in Dr Gu’s lab.

“The amount of heparin in a patch can be tailored to a patient’s specific needs and replaced daily, or less often, as needed. But the amount of heparin being released into the patient at any given moment will be determined by the thrombin levels in the patient’s blood.”

Experiments in mice

The researchers tested the patch in a mouse model of thrombosis. The mice were injected with large doses of thrombin (1000 U kg^-1) to induce an acute thromboembolism, which can lead to death in about 92% of mice.

The mice were then randomized into 5 different treatment groups:

• Intravenous heparin injection
• Empty HA microneedle patch
• HA microneedle patch encapsulating free heparin
• Thrombin-responsive HA-heparin microneedle patch
• Non-responsive HA-heparin microneedle patch (heparin dose: 200 U kg⁻¹).

The mice that received heparin via injection were treated before thrombosis induction. The microneedle patches were applied to the dorsum skin of the mice 10 minutes before the challenge.

All of the mice with the HA microneedle patch or the non-responsive HA-heparin microneedle patch died within 15 minutes of the thrombin injection.

All of the mice that received the heparin injection, heparin microneedle patch, or the thrombin-responsive HA-heparin microneedle patch survived the 15 minutes.

In a second experiment, mice received a thrombin injection 6 hours after treatment, and treatment consisted of:

• Heparin injection
• HA microneedle patch encapsulating free heparin
• Thrombin-responsive HA-heparin microneedle patch.

Fifteen minutes after the thrombin injection, death had occurred in 80% or more of the mice that received the heparin injection and the mice treated with the heparin microneedle patch.

But all of the mice treated with the thrombin-responsive HA-heparin microneedle patch survived.

The researchers also noted that staining of lung sections revealed the “superior anticoagulant capacity” of the thrombin-responsive HA-heparin microneedle patch.

The team observed “insignificant differences” in the lungs of healthy mice and mice treated with the thrombin-responsive HA-heparin microneedle patch.

However, mice that received a heparin injection or treatment with the heparin microneedle patch had intravascular and interstitial hemorrhage, blocked blood vessels, and atelectasis.

“We’re excited about the possibility of using a closed-loop, self-regulating smart patch to help treat a condition that affects thousands of people every year, while hopefully also driving down treatment costs,” Dr Gu said. “This paper represents a good first step, and we’re now looking for funding to perform additional preclinical testing.”

NCCN Guidelines for Patients®:

Nausea and Vomiting

©NCCN® 2016

The National Comprehensive Cancer Network (NCCN) has released new educational materials designed to help cancer patients combat nausea and vomiting.

The NCCN Guidelines for Patients® for Nausea and Vomiting and NCCN Quick Guide™ for Nausea and Vomiting are the first patient resources from NCCN to focus specifically on supportive care.

The resources are available on NCCN.org/patients and via the NCCN Patient Guides for Cancer mobile app.

NCCN Guidelines for Patients are patient-friendly translations of the NCCN Clinical Practice Guidelines in Oncology. Each resource features guidance from US cancer centers designed to help people living with cancer talk with their physicians about the best treatment options for their disease.

NCCN Quick Guide™ sheets are 1-page summaries of key points in the patient guidelines. They include elements such as “questions to ask your doctor,” a glossary of terms, and medical illustrations of anatomy, tests, and treatments.

The NCCN Guidelines for Patients for Nausea and Vomiting:

• Explain how these side effects are related to cancer treatment
• List cancer treatments that can cause nausea and vomiting
• Detail methods of preventing and treating these side effects
• Outline methods of coping with nausea and vomiting
• Provide a list of resources for information and support.

“At NCCN, our mission is to improve the lives of patients with cancer, and we are excited to be able to provide the information that will help patients better understand this common side effect of cancer treatment,” said Marcie R. Reeder, executive director of the NCCN Foundation.

“The NCCN Guidelines for Patients for Nausea and Vomiting are the first of a highly anticipated library of supportive care resources that provide patients with the same information their doctors use.”

NCCN Guidelines for Patients®:

Nausea and Vomiting

©NCCN® 2016

The National Comprehensive Cancer Network (NCCN) has released new educational materials designed to help cancer patients combat nausea and vomiting.

The NCCN Guidelines for Patients® for Nausea and Vomiting and NCCN Quick Guide™ for Nausea and Vomiting are the first patient resources from NCCN to focus specifically on supportive care.

The resources are available on NCCN.org/patients and via the NCCN Patient Guides for Cancer mobile app.

NCCN Guidelines for Patients are patient-friendly translations of the NCCN Clinical Practice Guidelines in Oncology. Each resource features guidance from US cancer centers designed to help people living with cancer talk with their physicians about the best treatment options for their disease.

NCCN Quick Guide™ sheets are 1-page summaries of key points in the patient guidelines. They include elements such as “questions to ask your doctor,” a glossary of terms, and medical illustrations of anatomy, tests, and treatments.

The NCCN Guidelines for Patients for Nausea and Vomiting:

• Explain how these side effects are related to cancer treatment
• List cancer treatments that can cause nausea and vomiting
• Detail methods of preventing and treating these side effects
• Outline methods of coping with nausea and vomiting
• Provide a list of resources for information and support.

“At NCCN, our mission is to improve the lives of patients with cancer, and we are excited to be able to provide the information that will help patients better understand this common side effect of cancer treatment,” said Marcie R. Reeder, executive director of the NCCN Foundation.

“The NCCN Guidelines for Patients for Nausea and Vomiting are the first of a highly anticipated library of supportive care resources that provide patients with the same information their doctors use.”

NCCN Guidelines for Patients®:

Nausea and Vomiting

©NCCN® 2016

The National Comprehensive Cancer Network (NCCN) has released new educational materials designed to help cancer patients combat nausea and vomiting.

The NCCN Guidelines for Patients® for Nausea and Vomiting and NCCN Quick Guide™ for Nausea and Vomiting are the first patient resources from NCCN to focus specifically on supportive care.

The resources are available on NCCN.org/patients and via the NCCN Patient Guides for Cancer mobile app.

NCCN Guidelines for Patients are patient-friendly translations of the NCCN Clinical Practice Guidelines in Oncology. Each resource features guidance from US cancer centers designed to help people living with cancer talk with their physicians about the best treatment options for their disease.

NCCN Quick Guide™ sheets are 1-page summaries of key points in the patient guidelines. They include elements such as “questions to ask your doctor,” a glossary of terms, and medical illustrations of anatomy, tests, and treatments.

The NCCN Guidelines for Patients for Nausea and Vomiting:

• Explain how these side effects are related to cancer treatment
• List cancer treatments that can cause nausea and vomiting
• Detail methods of preventing and treating these side effects
• Outline methods of coping with nausea and vomiting
• Provide a list of resources for information and support.

“At NCCN, our mission is to improve the lives of patients with cancer, and we are excited to be able to provide the information that will help patients better understand this common side effect of cancer treatment,” said Marcie R. Reeder, executive director of the NCCN Foundation.

“The NCCN Guidelines for Patients for Nausea and Vomiting are the first of a highly anticipated library of supportive care resources that provide patients with the same information their doctors use.”

Testosterone cypionate

(Depo-Testosterone)

Starting testosterone treatment is associated with an increased risk of venous thromboembolism (VTE) that peaks within 6 months and declines thereafter, according to research published in The BMJ.

Previous studies have reported contradictory results regarding testosterone use and VTE.

Researchers involved in the current study believe that failure to investigate the timing and duration of testosterone use may explain the conflicting findings.

For this study, David Handelsman, MBBS, PhD, of the University of Sydney in New South Wales, Australia, and his colleagues set out to determine the risk of VTE associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.

The study involved data from 19,215 patients with confirmed VTE and 909,530 age-matched controls registered with the UK Clinical Practice Research Database between January 2001 and May 2013.

The researchers divided subjects into 3 mutually exclusive testosterone exposure groups: current treatment, recent treatment, and no treatment in the previous 2 years. The “current treatment” group was subdivided into durations of more or less than 6 months.

After adjusting for confounding factors, the researchers estimated rates of VTE.

The adjusted rate ratio of VTE was 1.25 for current testosterone treatment as compared to no testosterone treatment.

In the first 6 months of treatment, the rate ratio of VTE was 1.63, which corresponded to 10 additional cases of VTE above the base rate of 15.8 per 10,000 person-years.

The risk of VTE declined after more than 6 months of treatment and after treatment stopped. The rate ratio after more than 6 months of treatment was 1.00. After treatment stopped, the rate ratio was 0.68.

The researchers noted that this is an observational study, so no firm conclusions can be drawn about cause and effect. The team also stressed that the increased risks observed are temporary and still relatively low in absolute terms.

Nevertheless, they said their study suggests “a transient increase in the risk of venous thromboembolism that peaks during the first 3 to 6 months and declines gradually thereafter.”

The team said additional research is needed to confirm the temporal increase in the risk of VTE they observed as well as the absence of risk with long-term testosterone use.

Testosterone cypionate

(Depo-Testosterone)

Starting testosterone treatment is associated with an increased risk of venous thromboembolism (VTE) that peaks within 6 months and declines thereafter, according to research published in The BMJ.

Previous studies have reported contradictory results regarding testosterone use and VTE.

Researchers involved in the current study believe that failure to investigate the timing and duration of testosterone use may explain the conflicting findings.

For this study, David Handelsman, MBBS, PhD, of the University of Sydney in New South Wales, Australia, and his colleagues set out to determine the risk of VTE associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.

The study involved data from 19,215 patients with confirmed VTE and 909,530 age-matched controls registered with the UK Clinical Practice Research Database between January 2001 and May 2013.

The researchers divided subjects into 3 mutually exclusive testosterone exposure groups: current treatment, recent treatment, and no treatment in the previous 2 years. The “current treatment” group was subdivided into durations of more or less than 6 months.

After adjusting for confounding factors, the researchers estimated rates of VTE.

The adjusted rate ratio of VTE was 1.25 for current testosterone treatment as compared to no testosterone treatment.

In the first 6 months of treatment, the rate ratio of VTE was 1.63, which corresponded to 10 additional cases of VTE above the base rate of 15.8 per 10,000 person-years.

The risk of VTE declined after more than 6 months of treatment and after treatment stopped. The rate ratio after more than 6 months of treatment was 1.00. After treatment stopped, the rate ratio was 0.68.

The researchers noted that this is an observational study, so no firm conclusions can be drawn about cause and effect. The team also stressed that the increased risks observed are temporary and still relatively low in absolute terms.

Nevertheless, they said their study suggests “a transient increase in the risk of venous thromboembolism that peaks during the first 3 to 6 months and declines gradually thereafter.”

The team said additional research is needed to confirm the temporal increase in the risk of VTE they observed as well as the absence of risk with long-term testosterone use.

Testosterone cypionate

(Depo-Testosterone)

Starting testosterone treatment is associated with an increased risk of venous thromboembolism (VTE) that peaks within 6 months and declines thereafter, according to research published in The BMJ.

Previous studies have reported contradictory results regarding testosterone use and VTE.

Researchers involved in the current study believe that failure to investigate the timing and duration of testosterone use may explain the conflicting findings.

For this study, David Handelsman, MBBS, PhD, of the University of Sydney in New South Wales, Australia, and his colleagues set out to determine the risk of VTE associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.

The study involved data from 19,215 patients with confirmed VTE and 909,530 age-matched controls registered with the UK Clinical Practice Research Database between January 2001 and May 2013.

The researchers divided subjects into 3 mutually exclusive testosterone exposure groups: current treatment, recent treatment, and no treatment in the previous 2 years. The “current treatment” group was subdivided into durations of more or less than 6 months.

After adjusting for confounding factors, the researchers estimated rates of VTE.

The adjusted rate ratio of VTE was 1.25 for current testosterone treatment as compared to no testosterone treatment.

In the first 6 months of treatment, the rate ratio of VTE was 1.63, which corresponded to 10 additional cases of VTE above the base rate of 15.8 per 10,000 person-years.

The risk of VTE declined after more than 6 months of treatment and after treatment stopped. The rate ratio after more than 6 months of treatment was 1.00. After treatment stopped, the rate ratio was 0.68.

The researchers noted that this is an observational study, so no firm conclusions can be drawn about cause and effect. The team also stressed that the increased risks observed are temporary and still relatively low in absolute terms.

Nevertheless, they said their study suggests “a transient increase in the risk of venous thromboembolism that peaks during the first 3 to 6 months and declines gradually thereafter.”

The team said additional research is needed to confirm the temporal increase in the risk of VTE they observed as well as the absence of risk with long-term testosterone use.

A sickled red blood cell

beside a normal one

Image by Betty Pace

The European Commission (EC) has designated GBT440 as an orphan medicinal product for the treatment of sickle cell disease (SCD).

GBT440 is being developed as a potentially disease-modifying therapy for SCD. The drug works by increasing hemoglobin’s affinity for oxygen.

Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.

If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the drug may be capable of modifying the progression of SCD.

Preclinical research published in the British Journal of Haematology earlier this year suggests that GBT440 is disease-modifying.

Early results from an ongoing phase 1/2 study of GBT440, which were presented at the 2015 ASH Annual Meeting, appeared promising as well.

Results from that study suggest that GBT440 can increase hemoglobin levels while decreasing reticulocyte counts, erythropoietin levels, and sickle cell counts.

Researchers also found the drug to be well tolerated, with no serious adverse events attributed to GBT440.

“Receiving orphan designation from the EC marks a significant milestone both for the SCD community and for GBT [Global Blood Therapeutics Inc.],” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics Inc., the company developing GBT440.

“SCD is a devastatingly severe disease with limited treatment options, and this designation, together with our fast track and orphan drug designations by the United States Food and Drug Administration, reflect the recognition of the broader regulatory community of this urgent unmet medical need.”

The EC grants orphan designation to therapies intended to treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides the company developing a drug with regulatory and financial incentives, including protocol assistance, 10 years of market exclusivity once the drug is approved, and reductions in, or exemptions from, fees.

A sickled red blood cell

beside a normal one

Image by Betty Pace

The European Commission (EC) has designated GBT440 as an orphan medicinal product for the treatment of sickle cell disease (SCD).

GBT440 is being developed as a potentially disease-modifying therapy for SCD. The drug works by increasing hemoglobin’s affinity for oxygen.

Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.

If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the drug may be capable of modifying the progression of SCD.

Preclinical research published in the British Journal of Haematology earlier this year suggests that GBT440 is disease-modifying.

Early results from an ongoing phase 1/2 study of GBT440, which were presented at the 2015 ASH Annual Meeting, appeared promising as well.

Results from that study suggest that GBT440 can increase hemoglobin levels while decreasing reticulocyte counts, erythropoietin levels, and sickle cell counts.

Researchers also found the drug to be well tolerated, with no serious adverse events attributed to GBT440.

“Receiving orphan designation from the EC marks a significant milestone both for the SCD community and for GBT [Global Blood Therapeutics Inc.],” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics Inc., the company developing GBT440.

“SCD is a devastatingly severe disease with limited treatment options, and this designation, together with our fast track and orphan drug designations by the United States Food and Drug Administration, reflect the recognition of the broader regulatory community of this urgent unmet medical need.”

The EC grants orphan designation to therapies intended to treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides the company developing a drug with regulatory and financial incentives, including protocol assistance, 10 years of market exclusivity once the drug is approved, and reductions in, or exemptions from, fees.

A sickled red blood cell

beside a normal one

Image by Betty Pace

The European Commission (EC) has designated GBT440 as an orphan medicinal product for the treatment of sickle cell disease (SCD).

GBT440 is being developed as a potentially disease-modifying therapy for SCD. The drug works by increasing hemoglobin’s affinity for oxygen.

Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.

If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the drug may be capable of modifying the progression of SCD.

Preclinical research published in the British Journal of Haematology earlier this year suggests that GBT440 is disease-modifying.

Early results from an ongoing phase 1/2 study of GBT440, which were presented at the 2015 ASH Annual Meeting, appeared promising as well.

Results from that study suggest that GBT440 can increase hemoglobin levels while decreasing reticulocyte counts, erythropoietin levels, and sickle cell counts.

Researchers also found the drug to be well tolerated, with no serious adverse events attributed to GBT440.

“Receiving orphan designation from the EC marks a significant milestone both for the SCD community and for GBT [Global Blood Therapeutics Inc.],” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics Inc., the company developing GBT440.

“SCD is a devastatingly severe disease with limited treatment options, and this designation, together with our fast track and orphan drug designations by the United States Food and Drug Administration, reflect the recognition of the broader regulatory community of this urgent unmet medical need.”

The EC grants orphan designation to therapies intended to treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides the company developing a drug with regulatory and financial incentives, including protocol assistance, 10 years of market exclusivity once the drug is approved, and reductions in, or exemptions from, fees.

Pomalidomide (Pomalyst)

Photo from Business Wire

The National Institute for Health and Care Excellence (NICE) has issued a final appraisal determination recommending that pomalidomide be made available through the National Health Service (NHS).

NICE is recommending pomalidomide be available for use in combination with low-dose dexamethasone to treat adults with multiple myeloma who have received at least 3 previous treatments, including lenalidomide and bortezomib.

NICE previously evaluated pomalidomide in 2015 and said it could not recommend the drug, as analyses suggested pomalidomide doesn’t provide enough benefit to justify its high price.

Since that time, a committee advising NICE has reviewed additional data on pomalidomide.

And Celgene, the company that makes pomalidomide, has agreed to provide the NHS with a discount.

The cost of pomalidomide is £8884 per 21-tablet pack (excluding tax). The average cost of a course of treatment is £44,420 (excluding tax).

The discount Celgene will provide to the NHS is confidential.

NICE’s final appraisal determination on pomalidomide is now with consultees who have the opportunity to appeal against it. If there is no appeal, or an appeal is not upheld, the final appraisal determination is issued by NICE as a guidance.

The final guidance is expected in January 2017. Once NICE issues a final guidance on pomalidomide, the NHS must make the drug available within 3 months.

Pomalidomide (Pomalyst)

Photo from Business Wire

The National Institute for Health and Care Excellence (NICE) has issued a final appraisal determination recommending that pomalidomide be made available through the National Health Service (NHS).

NICE is recommending pomalidomide be available for use in combination with low-dose dexamethasone to treat adults with multiple myeloma who have received at least 3 previous treatments, including lenalidomide and bortezomib.

NICE previously evaluated pomalidomide in 2015 and said it could not recommend the drug, as analyses suggested pomalidomide doesn’t provide enough benefit to justify its high price.

Since that time, a committee advising NICE has reviewed additional data on pomalidomide.

And Celgene, the company that makes pomalidomide, has agreed to provide the NHS with a discount.

The cost of pomalidomide is £8884 per 21-tablet pack (excluding tax). The average cost of a course of treatment is £44,420 (excluding tax).

The discount Celgene will provide to the NHS is confidential.

NICE’s final appraisal determination on pomalidomide is now with consultees who have the opportunity to appeal against it. If there is no appeal, or an appeal is not upheld, the final appraisal determination is issued by NICE as a guidance.

The final guidance is expected in January 2017. Once NICE issues a final guidance on pomalidomide, the NHS must make the drug available within 3 months.

Pomalidomide (Pomalyst)

Photo from Business Wire

The National Institute for Health and Care Excellence (NICE) has issued a final appraisal determination recommending that pomalidomide be made available through the National Health Service (NHS).

NICE is recommending pomalidomide be available for use in combination with low-dose dexamethasone to treat adults with multiple myeloma who have received at least 3 previous treatments, including lenalidomide and bortezomib.

NICE previously evaluated pomalidomide in 2015 and said it could not recommend the drug, as analyses suggested pomalidomide doesn’t provide enough benefit to justify its high price.

Since that time, a committee advising NICE has reviewed additional data on pomalidomide.

And Celgene, the company that makes pomalidomide, has agreed to provide the NHS with a discount.

The cost of pomalidomide is £8884 per 21-tablet pack (excluding tax). The average cost of a course of treatment is £44,420 (excluding tax).

The discount Celgene will provide to the NHS is confidential.

NICE’s final appraisal determination on pomalidomide is now with consultees who have the opportunity to appeal against it. If there is no appeal, or an appeal is not upheld, the final appraisal determination is issued by NICE as a guidance.

The final guidance is expected in January 2017. Once NICE issues a final guidance on pomalidomide, the NHS must make the drug available within 3 months.

Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).

Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.

Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m^2.

Source: American Gastroenterological Association

Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).

Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.

Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”

The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.

Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).

Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.

Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m^2.

Source: American Gastroenterological Association

Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).

Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.

Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”

The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.

Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).

Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.

Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m^2.

Source: American Gastroenterological Association

Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).

Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.

Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”

The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.

Mobile health indexes for remotely monitoring Crohn’s disease and ulcerative colitis accurately identified clinically active disease and changed significantly as disease activity did, researchers reported in the December issue of Clinical Gastroenterology and Hepatology.

The mobile health index for Crohn’s disease predicted clinical disease activity with an area under the receiver operating characteristic curve (AUC) of 0.90, Welmoed K. van Deen, MD, of the University of California, Los Angeles, and her associates wrote in Clinical Gastroenterology and Hepatology. The AUC for the ulcerative colitis index for ulcerative colitis was very similar, at 0.91. “The [mobile health indexes] are specifically designed for implementation on a mobile application, and are currently available to patients with IBD [inflammatory bowel disease] treated at the UCLA Center for IBD,” the researchers said. “Prospective, randomized studies need to assess the effect of remote monitoring on disease control, quality of life, patient satisfaction, and health care costs.”

Inspired by the lack of smartphone applications for remotely managing inflammatory bowel disease, the researchers administered comprehensive disease-specific questionnaires to 110 patients with Crohn’s disease and 109 patients with ulcerative colitis who visited the UCLA IBD center in 2013 and 2014. They compared patient-reported outcomes across 10 domains of disease activity with scores on a number of existing disease activity indexes, and used logistic regression to identify which self-reported outcomes best predicted disease activity in both Crohn’s disease and ulcerative colitis (Clin Gastroenterol Hepatol. 2015 Nov 18. doi: 10.1016/j.cgh.2015.10.035).

The resulting Crohn’s disease mobile health index asked how many liquid or “very soft” stools patients had per day, if they had abdominal pain, and how they would rate their well-being and level of disease control on scales ranging between 0 and 10. The ulcerative colitis mobile health index asked about number of stools the day before and had patients score abdominal pain, frequency of rectal bleeding, and level of disease control between 0 and 10. The researchers also validated each mobile health index in multicenter cohorts of 301 patients with Crohn’s disease and 265 patients with ulcerative colitis.

Each mobile health index detected clinical disease activity with about 90% accuracy, compared with standard measures, including the Crohn’s disease activity index and the Harvey Bradshaw index for Crohn’s disease, the partial Mayo score, the simple clinical colitis activity index, and the modified Truelove and Witts index for ulcerative colitis. But the mobile indexes detected endoscopic disease activity less accurately, with AUCs of 0.82 for ulcerative colitis and only 0.63 for Crohn’s disease. “As previously shown, ulcerative colitis clinical disease activity highly correlates with endoscopic disease activity, whereas correlation between Crohn’s disease symptoms and endoscopic findings is poor,” the researchers noted. However, both mobile indexes reliably detected changes in disease activity, varying significantly depending on whether patients were clinically improved, stable, or worse, regardless of whether they had Crohn’s disease (P = .003) or ulcerative colitis (P = .0025).

To explore intrapatient reliability, the researchers also compared initial and follow-up mobile health index results for subgroups of 40 Crohn’s disease patients tested a median of 21 hours apart, and 37 ulcerative colitis patients tested a median of 23 hours apart. In both cases, the intraclass correlation coefficient reached 0.94 (95% confidence interval, 0.89-0.97). “Cloud-based health technologies are predicted to revolutionize care delivery and patient engagement,” the investigators commented. “Patients can participate in their care by signaling meaningful health outcomes during year-round monitoring. Barriers for more widespread implementation of mobile health in inflammatory bowel disease care include policies affecting reimbursement and regulatory requirements, and privacy and security concerns.”

Genova Diagnostics provided stool collection kits and fecal calprotectin testing. The investigators had no disclosures.

Mobile health indexes for remotely monitoring Crohn’s disease and ulcerative colitis accurately identified clinically active disease and changed significantly as disease activity did, researchers reported in the December issue of Clinical Gastroenterology and Hepatology.

The mobile health index for Crohn’s disease predicted clinical disease activity with an area under the receiver operating characteristic curve (AUC) of 0.90, Welmoed K. van Deen, MD, of the University of California, Los Angeles, and her associates wrote in Clinical Gastroenterology and Hepatology. The AUC for the ulcerative colitis index for ulcerative colitis was very similar, at 0.91. “The [mobile health indexes] are specifically designed for implementation on a mobile application, and are currently available to patients with IBD [inflammatory bowel disease] treated at the UCLA Center for IBD,” the researchers said. “Prospective, randomized studies need to assess the effect of remote monitoring on disease control, quality of life, patient satisfaction, and health care costs.”

Inspired by the lack of smartphone applications for remotely managing inflammatory bowel disease, the researchers administered comprehensive disease-specific questionnaires to 110 patients with Crohn’s disease and 109 patients with ulcerative colitis who visited the UCLA IBD center in 2013 and 2014. They compared patient-reported outcomes across 10 domains of disease activity with scores on a number of existing disease activity indexes, and used logistic regression to identify which self-reported outcomes best predicted disease activity in both Crohn’s disease and ulcerative colitis (Clin Gastroenterol Hepatol. 2015 Nov 18. doi: 10.1016/j.cgh.2015.10.035).

The resulting Crohn’s disease mobile health index asked how many liquid or “very soft” stools patients had per day, if they had abdominal pain, and how they would rate their well-being and level of disease control on scales ranging between 0 and 10. The ulcerative colitis mobile health index asked about number of stools the day before and had patients score abdominal pain, frequency of rectal bleeding, and level of disease control between 0 and 10. The researchers also validated each mobile health index in multicenter cohorts of 301 patients with Crohn’s disease and 265 patients with ulcerative colitis.

Each mobile health index detected clinical disease activity with about 90% accuracy, compared with standard measures, including the Crohn’s disease activity index and the Harvey Bradshaw index for Crohn’s disease, the partial Mayo score, the simple clinical colitis activity index, and the modified Truelove and Witts index for ulcerative colitis. But the mobile indexes detected endoscopic disease activity less accurately, with AUCs of 0.82 for ulcerative colitis and only 0.63 for Crohn’s disease. “As previously shown, ulcerative colitis clinical disease activity highly correlates with endoscopic disease activity, whereas correlation between Crohn’s disease symptoms and endoscopic findings is poor,” the researchers noted. However, both mobile indexes reliably detected changes in disease activity, varying significantly depending on whether patients were clinically improved, stable, or worse, regardless of whether they had Crohn’s disease (P = .003) or ulcerative colitis (P = .0025).

To explore intrapatient reliability, the researchers also compared initial and follow-up mobile health index results for subgroups of 40 Crohn’s disease patients tested a median of 21 hours apart, and 37 ulcerative colitis patients tested a median of 23 hours apart. In both cases, the intraclass correlation coefficient reached 0.94 (95% confidence interval, 0.89-0.97). “Cloud-based health technologies are predicted to revolutionize care delivery and patient engagement,” the investigators commented. “Patients can participate in their care by signaling meaningful health outcomes during year-round monitoring. Barriers for more widespread implementation of mobile health in inflammatory bowel disease care include policies affecting reimbursement and regulatory requirements, and privacy and security concerns.”

Genova Diagnostics provided stool collection kits and fecal calprotectin testing. The investigators had no disclosures.

Mobile health indexes for remotely monitoring Crohn’s disease and ulcerative colitis accurately identified clinically active disease and changed significantly as disease activity did, researchers reported in the December issue of Clinical Gastroenterology and Hepatology.

The mobile health index for Crohn’s disease predicted clinical disease activity with an area under the receiver operating characteristic curve (AUC) of 0.90, Welmoed K. van Deen, MD, of the University of California, Los Angeles, and her associates wrote in Clinical Gastroenterology and Hepatology. The AUC for the ulcerative colitis index for ulcerative colitis was very similar, at 0.91. “The [mobile health indexes] are specifically designed for implementation on a mobile application, and are currently available to patients with IBD [inflammatory bowel disease] treated at the UCLA Center for IBD,” the researchers said. “Prospective, randomized studies need to assess the effect of remote monitoring on disease control, quality of life, patient satisfaction, and health care costs.”

Inspired by the lack of smartphone applications for remotely managing inflammatory bowel disease, the researchers administered comprehensive disease-specific questionnaires to 110 patients with Crohn’s disease and 109 patients with ulcerative colitis who visited the UCLA IBD center in 2013 and 2014. They compared patient-reported outcomes across 10 domains of disease activity with scores on a number of existing disease activity indexes, and used logistic regression to identify which self-reported outcomes best predicted disease activity in both Crohn’s disease and ulcerative colitis (Clin Gastroenterol Hepatol. 2015 Nov 18. doi: 10.1016/j.cgh.2015.10.035).

The resulting Crohn’s disease mobile health index asked how many liquid or “very soft” stools patients had per day, if they had abdominal pain, and how they would rate their well-being and level of disease control on scales ranging between 0 and 10. The ulcerative colitis mobile health index asked about number of stools the day before and had patients score abdominal pain, frequency of rectal bleeding, and level of disease control between 0 and 10. The researchers also validated each mobile health index in multicenter cohorts of 301 patients with Crohn’s disease and 265 patients with ulcerative colitis.

Each mobile health index detected clinical disease activity with about 90% accuracy, compared with standard measures, including the Crohn’s disease activity index and the Harvey Bradshaw index for Crohn’s disease, the partial Mayo score, the simple clinical colitis activity index, and the modified Truelove and Witts index for ulcerative colitis. But the mobile indexes detected endoscopic disease activity less accurately, with AUCs of 0.82 for ulcerative colitis and only 0.63 for Crohn’s disease. “As previously shown, ulcerative colitis clinical disease activity highly correlates with endoscopic disease activity, whereas correlation between Crohn’s disease symptoms and endoscopic findings is poor,” the researchers noted. However, both mobile indexes reliably detected changes in disease activity, varying significantly depending on whether patients were clinically improved, stable, or worse, regardless of whether they had Crohn’s disease (P = .003) or ulcerative colitis (P = .0025).

To explore intrapatient reliability, the researchers also compared initial and follow-up mobile health index results for subgroups of 40 Crohn’s disease patients tested a median of 21 hours apart, and 37 ulcerative colitis patients tested a median of 23 hours apart. In both cases, the intraclass correlation coefficient reached 0.94 (95% confidence interval, 0.89-0.97). “Cloud-based health technologies are predicted to revolutionize care delivery and patient engagement,” the investigators commented. “Patients can participate in their care by signaling meaningful health outcomes during year-round monitoring. Barriers for more widespread implementation of mobile health in inflammatory bowel disease care include policies affecting reimbursement and regulatory requirements, and privacy and security concerns.”

Genova Diagnostics provided stool collection kits and fecal calprotectin testing. The investigators had no disclosures.