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FDA reaffirms rivaroxaban’s atrial fib efficacy in ROCKET AF
The Food and Drug Administration reaffirmed its confidence in the data supporting the claim that rivaroxaban (Xarelto) is a safe and effective alternative to warfarin for preventing strokes and blood clots in patients with nonvalvular atrial fibrillation.
“The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation,” the agency said in a statement released on Oct. 11.
In response to these events the FDA “completed a variety of analyses to assess the impact that this faulty monitoring device had on the ROCKET AF study results. The agency has determined that effects on strokes or bleeding, including bleeding in the head, were minimal,” the agency said in its statement.
Researchers associated with ROCKET AF published their own analysis of the impact of the faulty device on bleeding rates among patients treated with warfarin in the trial and concluded that device malfunction did not appear to influence the results (N Engl J Med. 2016 Feb 25;374[8]:785-8).
Rivaroxaban is one of four new oral anticoagulants (NOACs) on the U.S. market that are alternatives to warfarin for stroke and clot prevention in patients with nonvalvular atrial fibrillation. An analysis of 2014 data on U.S. office-based prescriptions for NOACs in atrial fibrillation patients showed that rivaroxaban was by far the most commonly prescribed drug in the class, prescribed for patients during 48% of physician office visits that led to a NOAC prescription (Am J Med. 2015 Dec;128[12]:1300-5).
[email protected]
On Twitter @mitchelzoler
The Food and Drug Administration reaffirmed its confidence in the data supporting the claim that rivaroxaban (Xarelto) is a safe and effective alternative to warfarin for preventing strokes and blood clots in patients with nonvalvular atrial fibrillation.
“The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation,” the agency said in a statement released on Oct. 11.
In response to these events the FDA “completed a variety of analyses to assess the impact that this faulty monitoring device had on the ROCKET AF study results. The agency has determined that effects on strokes or bleeding, including bleeding in the head, were minimal,” the agency said in its statement.
Researchers associated with ROCKET AF published their own analysis of the impact of the faulty device on bleeding rates among patients treated with warfarin in the trial and concluded that device malfunction did not appear to influence the results (N Engl J Med. 2016 Feb 25;374[8]:785-8).
Rivaroxaban is one of four new oral anticoagulants (NOACs) on the U.S. market that are alternatives to warfarin for stroke and clot prevention in patients with nonvalvular atrial fibrillation. An analysis of 2014 data on U.S. office-based prescriptions for NOACs in atrial fibrillation patients showed that rivaroxaban was by far the most commonly prescribed drug in the class, prescribed for patients during 48% of physician office visits that led to a NOAC prescription (Am J Med. 2015 Dec;128[12]:1300-5).
[email protected]
On Twitter @mitchelzoler
The Food and Drug Administration reaffirmed its confidence in the data supporting the claim that rivaroxaban (Xarelto) is a safe and effective alternative to warfarin for preventing strokes and blood clots in patients with nonvalvular atrial fibrillation.
“The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation,” the agency said in a statement released on Oct. 11.
In response to these events the FDA “completed a variety of analyses to assess the impact that this faulty monitoring device had on the ROCKET AF study results. The agency has determined that effects on strokes or bleeding, including bleeding in the head, were minimal,” the agency said in its statement.
Researchers associated with ROCKET AF published their own analysis of the impact of the faulty device on bleeding rates among patients treated with warfarin in the trial and concluded that device malfunction did not appear to influence the results (N Engl J Med. 2016 Feb 25;374[8]:785-8).
Rivaroxaban is one of four new oral anticoagulants (NOACs) on the U.S. market that are alternatives to warfarin for stroke and clot prevention in patients with nonvalvular atrial fibrillation. An analysis of 2014 data on U.S. office-based prescriptions for NOACs in atrial fibrillation patients showed that rivaroxaban was by far the most commonly prescribed drug in the class, prescribed for patients during 48% of physician office visits that led to a NOAC prescription (Am J Med. 2015 Dec;128[12]:1300-5).
[email protected]
On Twitter @mitchelzoler
Hanging on as small practices slowly die
I’ve had to skip several paychecks this year to keep my practice afloat. That makes it hard to pay for my routine personal expenses, like a mortgage, so I have to take the money out of my family’s “rainy day” savings.
This gets old after a few years of the same cycle. I’m pretty sick of it.
Granted, I chose this path. Solo practice suits me. I’ve been in a large group, and it took me roughly 2 years to realize it was a poor fit for me. I’ve been on my own since 2000 and been pretty happy here.
I’ve come to accept that taking a vacation means a temporary drop in salary down the road. My family is important to me, and I don’t want them to remember me as the never-home father immortalized by Harry Chapin’s “Cat’s in the Cradle.”
Trouble is this: What if you still work hard, and find your income falling? I see patients from 8 to 4 most days, with a full schedule, but reimbursements keep dropping and costs keep climbing. Isn’t the idea that hard work will bring success central to the American Dream? Especially when you toss in 9 years of medical school and residency? Apparently not. The American Dream, whatever it is, is pretty much dead for most small-practice doctors.
These are tough times for solo docs, regardless of field. I’ve seen several posts on sites such as Sermo that show I’m not the only one in this boat, skipping paychecks to keep the door open and lights on. Most small practices are running into the same issue. Some, like me, are slugging it out and hoping things get better. Others are folding up and moving, or joining large groups, or signing up with a hospital system.
I’m not sure those last two are options I want. Most of the docs I know who’ve joined hospital outpatient systems are pretty unhappy with them, too. They talk about computer systems designed for billing rather than patient care; unrealistic amounts of time allotted to each patient by a nonmedical person; and jumping through hoops to get certain tests or treatments done.
I suspect it’s a combination of factors, though others see more sinister forces at work. Some posts I read suggest that it’s part of a government and/or insurance conspiracy to destroy small practices.
Regardless, it seems to be succeeding. Small practices are in crisis. Doctor suicides are up. And solo practice has been found to be a risk factor for suicide. There are days when I can see how that seems like the only way out for those who came here just to care for people, and now find that economic circumstances won’t let them.
I don’t have a castle, or drive a Rolls-Royce, or send my kids to private school. We live fairly modestly, but even then it’s getting hard to keep up with costs.
We’re in an election year, and, as always, medical care is bandied about by both parties as a bargaining chip to get votes. But I haven’t heard either side talk about this, nor do I get the impression that either major candidate really cares. Both of them, and members of Congress, get pretty top-notch care without having to worry about cost. This isn’t reassuring to me and all the other solo docs hanging on by our fingernails and trying to practice ethical, honest medicine.
I’m sure some will say it’s progress, but I think the gradual death of the American small and solo practice is sad. It’s a model that’s been the backbone of Western medicine for a few hundred years now, caring for people in big cities, small towns, and everywhere in between. Portrayed in fiction as Marcus Welby, Michaela Quinn, Joel Fleischman, and (my favorite, from Willa Cather’s “Neighbour Rosicky”) Ed Burleigh. Sometimes brilliant, sometimes quirky, sometimes all-too-human ... but still doctors, caring for their patients and communities.
Like the unnamed protagonist in Dr. Seuss’ “I Had Trouble in getting to Solla Sollew,” I tend to find that no matter where you go there will be troubles, and sometimes you’re best off staying in one place and fighting the ones you know.
And, for now, that’s where I am and hope to stay. But I’m scared.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I’ve had to skip several paychecks this year to keep my practice afloat. That makes it hard to pay for my routine personal expenses, like a mortgage, so I have to take the money out of my family’s “rainy day” savings.
This gets old after a few years of the same cycle. I’m pretty sick of it.
Granted, I chose this path. Solo practice suits me. I’ve been in a large group, and it took me roughly 2 years to realize it was a poor fit for me. I’ve been on my own since 2000 and been pretty happy here.
I’ve come to accept that taking a vacation means a temporary drop in salary down the road. My family is important to me, and I don’t want them to remember me as the never-home father immortalized by Harry Chapin’s “Cat’s in the Cradle.”
Trouble is this: What if you still work hard, and find your income falling? I see patients from 8 to 4 most days, with a full schedule, but reimbursements keep dropping and costs keep climbing. Isn’t the idea that hard work will bring success central to the American Dream? Especially when you toss in 9 years of medical school and residency? Apparently not. The American Dream, whatever it is, is pretty much dead for most small-practice doctors.
These are tough times for solo docs, regardless of field. I’ve seen several posts on sites such as Sermo that show I’m not the only one in this boat, skipping paychecks to keep the door open and lights on. Most small practices are running into the same issue. Some, like me, are slugging it out and hoping things get better. Others are folding up and moving, or joining large groups, or signing up with a hospital system.
I’m not sure those last two are options I want. Most of the docs I know who’ve joined hospital outpatient systems are pretty unhappy with them, too. They talk about computer systems designed for billing rather than patient care; unrealistic amounts of time allotted to each patient by a nonmedical person; and jumping through hoops to get certain tests or treatments done.
I suspect it’s a combination of factors, though others see more sinister forces at work. Some posts I read suggest that it’s part of a government and/or insurance conspiracy to destroy small practices.
Regardless, it seems to be succeeding. Small practices are in crisis. Doctor suicides are up. And solo practice has been found to be a risk factor for suicide. There are days when I can see how that seems like the only way out for those who came here just to care for people, and now find that economic circumstances won’t let them.
I don’t have a castle, or drive a Rolls-Royce, or send my kids to private school. We live fairly modestly, but even then it’s getting hard to keep up with costs.
We’re in an election year, and, as always, medical care is bandied about by both parties as a bargaining chip to get votes. But I haven’t heard either side talk about this, nor do I get the impression that either major candidate really cares. Both of them, and members of Congress, get pretty top-notch care without having to worry about cost. This isn’t reassuring to me and all the other solo docs hanging on by our fingernails and trying to practice ethical, honest medicine.
I’m sure some will say it’s progress, but I think the gradual death of the American small and solo practice is sad. It’s a model that’s been the backbone of Western medicine for a few hundred years now, caring for people in big cities, small towns, and everywhere in between. Portrayed in fiction as Marcus Welby, Michaela Quinn, Joel Fleischman, and (my favorite, from Willa Cather’s “Neighbour Rosicky”) Ed Burleigh. Sometimes brilliant, sometimes quirky, sometimes all-too-human ... but still doctors, caring for their patients and communities.
Like the unnamed protagonist in Dr. Seuss’ “I Had Trouble in getting to Solla Sollew,” I tend to find that no matter where you go there will be troubles, and sometimes you’re best off staying in one place and fighting the ones you know.
And, for now, that’s where I am and hope to stay. But I’m scared.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I’ve had to skip several paychecks this year to keep my practice afloat. That makes it hard to pay for my routine personal expenses, like a mortgage, so I have to take the money out of my family’s “rainy day” savings.
This gets old after a few years of the same cycle. I’m pretty sick of it.
Granted, I chose this path. Solo practice suits me. I’ve been in a large group, and it took me roughly 2 years to realize it was a poor fit for me. I’ve been on my own since 2000 and been pretty happy here.
I’ve come to accept that taking a vacation means a temporary drop in salary down the road. My family is important to me, and I don’t want them to remember me as the never-home father immortalized by Harry Chapin’s “Cat’s in the Cradle.”
Trouble is this: What if you still work hard, and find your income falling? I see patients from 8 to 4 most days, with a full schedule, but reimbursements keep dropping and costs keep climbing. Isn’t the idea that hard work will bring success central to the American Dream? Especially when you toss in 9 years of medical school and residency? Apparently not. The American Dream, whatever it is, is pretty much dead for most small-practice doctors.
These are tough times for solo docs, regardless of field. I’ve seen several posts on sites such as Sermo that show I’m not the only one in this boat, skipping paychecks to keep the door open and lights on. Most small practices are running into the same issue. Some, like me, are slugging it out and hoping things get better. Others are folding up and moving, or joining large groups, or signing up with a hospital system.
I’m not sure those last two are options I want. Most of the docs I know who’ve joined hospital outpatient systems are pretty unhappy with them, too. They talk about computer systems designed for billing rather than patient care; unrealistic amounts of time allotted to each patient by a nonmedical person; and jumping through hoops to get certain tests or treatments done.
I suspect it’s a combination of factors, though others see more sinister forces at work. Some posts I read suggest that it’s part of a government and/or insurance conspiracy to destroy small practices.
Regardless, it seems to be succeeding. Small practices are in crisis. Doctor suicides are up. And solo practice has been found to be a risk factor for suicide. There are days when I can see how that seems like the only way out for those who came here just to care for people, and now find that economic circumstances won’t let them.
I don’t have a castle, or drive a Rolls-Royce, or send my kids to private school. We live fairly modestly, but even then it’s getting hard to keep up with costs.
We’re in an election year, and, as always, medical care is bandied about by both parties as a bargaining chip to get votes. But I haven’t heard either side talk about this, nor do I get the impression that either major candidate really cares. Both of them, and members of Congress, get pretty top-notch care without having to worry about cost. This isn’t reassuring to me and all the other solo docs hanging on by our fingernails and trying to practice ethical, honest medicine.
I’m sure some will say it’s progress, but I think the gradual death of the American small and solo practice is sad. It’s a model that’s been the backbone of Western medicine for a few hundred years now, caring for people in big cities, small towns, and everywhere in between. Portrayed in fiction as Marcus Welby, Michaela Quinn, Joel Fleischman, and (my favorite, from Willa Cather’s “Neighbour Rosicky”) Ed Burleigh. Sometimes brilliant, sometimes quirky, sometimes all-too-human ... but still doctors, caring for their patients and communities.
Like the unnamed protagonist in Dr. Seuss’ “I Had Trouble in getting to Solla Sollew,” I tend to find that no matter where you go there will be troubles, and sometimes you’re best off staying in one place and fighting the ones you know.
And, for now, that’s where I am and hope to stay. But I’m scared.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Brief screen helps identify patients with PTSD, depression
WAIKOLOA, HAWAII – A new nine-item tool known as the Injured Trauma Survivor Screen demonstrated strong sensitivity and specificity for predicting posttraumatic stress disorder and depression in trauma patients.
At the annual meeting of the American Association for the Surgery of Trauma, Terri deRoon-Cassini, PhD, said that the rates of PTSD among trauma patients range from 10% to 42%, depending on the type of injury sustained. “There is significant life impairment, including an increased risk for suicide and an increased risk for morbidity and mortality,” said Dr. deRoon-Cassini, a clinical psychologist and associate professor with the division of trauma and critical care at the Medical College of Wisconsin, Milwaukee.
The ACS Committee on Trauma currently recommends PTSD screening by trauma centers, including the 20-item PTSD Checklist and the nine-item PHD-9 for depression. However, these symptom-based screens were not validated in hospitalized trauma patients. “This becomes important, because according to the symptom trajectory of PTSD after trauma, about 22% of people experience chronic disease and about 16%-18% of people who have symptoms at baseline do not translate to symptoms by 6 months, so screening with a symptom-based measure isn’t always the best route,” she said.
In an effort to create a brief screening tool to identify those at risk for PTSD and depression following traumatic injury, Dr. deRoon-Cassini and her associates scoured existing medical literature on the topic to review risk factors and created an item pool of questions based on those risk factors. They came up with 47 items and statistically “funneled out the items to create the most parsimonious model predicting who goes on to develop PTSD and depression separately,” she explained. They then created the Injured Trauma Survivor Screen (ITSS), a nine-item list of yes/no questions that takes about 5 minutes to administer: five items for PTSD and five items for depression, with one item that overlaps. The five ITSS PTSD questions are:
• Did you think you were going to die? (risk factor being perceived life threat; odds ratio 6.32).
• Do you think this was done to you intentionally? (risk factor being intentionality; OR, 4.24).
• Have you felt more restless, tense, or jumpy than usual? (risk factor being assessment of arousal; OR, 5.31).
• Have you found yourself unable to stop worrying? (risk factor being worry/rumination; OR, 4.49).
• Do you find yourself thinking that the world is unsafe and that people are not to be trusted? (risk factor being negative alterations in cognition; OR, 5.52).
The five ITSS depression questions are:
• Have you ever taken medication for, or been given a mental health diagnosis? (risk factor being preexisting psychopathology; OR, 10.58).
• Has there ever been a time in your life you have been bothered by feeling down or hopeless or lost all interest in things you usually enjoyed for more than 2 weeks? (risk factor being premorbid depression; OR, 3.78).
• Did you think you were going to die? (risk factor being perceived life threat; OR, 9.69).
• Have you felt emotionally detached from your loved ones? (risk factor being negative alteration in mood; OR, 8.03).
• Do you find yourself crying and are unsure why? (risk factor being mood/depression; OR, 9.18).
The researchers administered the survey to 139 patients at two trauma centers. More than half (69%) were male, 48% were white, 40% were African American, and the remainder were from other ethnic backgrounds. The three most common mechanisms of injury were motor vehicle crashes (29%), motorcycle/all-terrain vehicle crashes (19%), and falls (13%). Dr. deRoon-Cassini reported that administration of the ITSS within 4 days of injury demonstrated a 75% sensitivity for identifying the risk for PTSD and depression, a 94% specificity for PTSD, and a 96% specificity for depression, with a cutoff score of 2 out of 5 for both subscales based on a receiver operating characteristic (ROC) curve analysis.
One month following administration of the ITSS, 20% of patients were diagnosed with depression and 29% were diagnosed with PTSD. Of those diagnosed with PTSD, 55% met criteria for concomitant depression “so we are seeing a high comorbidity between PTSD and depression, which is consistent with the medical literature,” she said.
“The ITSS represents a brief way that we can screen for PTSD and depression within a trauma system,” Dr. deRoon-Cassini said. “At our institution, social workers administer the tool. They have a flow sheet in our EMR system where they enter the responses. If someone screens positive, a best practice recommendation is put into the patient’s chart, which gets funneled to a trauma psychology consult. On the treatment side we try to intervene by triaging the severity of the current distress the person is experiencing, past comorbidities, and past trauma histories. From there we decide whether to do a brief intervention or more intensive evidence-based interventions for PTSD or depression together or separately.”
The study was funded by a grant from the Medical College of Wisconsin. Coauthors included Joshua Hunt, PhD, of the Medical College of Wisconsin, Milwaukee; Ann Marie Warren, PhD, of Baylor Medical Center, Dallas; and Karen Brasel, MD, FACS, of Oregon Health & Science University, Portland. Dr. deRoon-Cassini reported having no financial disclosures.
WAIKOLOA, HAWAII – A new nine-item tool known as the Injured Trauma Survivor Screen demonstrated strong sensitivity and specificity for predicting posttraumatic stress disorder and depression in trauma patients.
At the annual meeting of the American Association for the Surgery of Trauma, Terri deRoon-Cassini, PhD, said that the rates of PTSD among trauma patients range from 10% to 42%, depending on the type of injury sustained. “There is significant life impairment, including an increased risk for suicide and an increased risk for morbidity and mortality,” said Dr. deRoon-Cassini, a clinical psychologist and associate professor with the division of trauma and critical care at the Medical College of Wisconsin, Milwaukee.
The ACS Committee on Trauma currently recommends PTSD screening by trauma centers, including the 20-item PTSD Checklist and the nine-item PHD-9 for depression. However, these symptom-based screens were not validated in hospitalized trauma patients. “This becomes important, because according to the symptom trajectory of PTSD after trauma, about 22% of people experience chronic disease and about 16%-18% of people who have symptoms at baseline do not translate to symptoms by 6 months, so screening with a symptom-based measure isn’t always the best route,” she said.
In an effort to create a brief screening tool to identify those at risk for PTSD and depression following traumatic injury, Dr. deRoon-Cassini and her associates scoured existing medical literature on the topic to review risk factors and created an item pool of questions based on those risk factors. They came up with 47 items and statistically “funneled out the items to create the most parsimonious model predicting who goes on to develop PTSD and depression separately,” she explained. They then created the Injured Trauma Survivor Screen (ITSS), a nine-item list of yes/no questions that takes about 5 minutes to administer: five items for PTSD and five items for depression, with one item that overlaps. The five ITSS PTSD questions are:
• Did you think you were going to die? (risk factor being perceived life threat; odds ratio 6.32).
• Do you think this was done to you intentionally? (risk factor being intentionality; OR, 4.24).
• Have you felt more restless, tense, or jumpy than usual? (risk factor being assessment of arousal; OR, 5.31).
• Have you found yourself unable to stop worrying? (risk factor being worry/rumination; OR, 4.49).
• Do you find yourself thinking that the world is unsafe and that people are not to be trusted? (risk factor being negative alterations in cognition; OR, 5.52).
The five ITSS depression questions are:
• Have you ever taken medication for, or been given a mental health diagnosis? (risk factor being preexisting psychopathology; OR, 10.58).
• Has there ever been a time in your life you have been bothered by feeling down or hopeless or lost all interest in things you usually enjoyed for more than 2 weeks? (risk factor being premorbid depression; OR, 3.78).
• Did you think you were going to die? (risk factor being perceived life threat; OR, 9.69).
• Have you felt emotionally detached from your loved ones? (risk factor being negative alteration in mood; OR, 8.03).
• Do you find yourself crying and are unsure why? (risk factor being mood/depression; OR, 9.18).
The researchers administered the survey to 139 patients at two trauma centers. More than half (69%) were male, 48% were white, 40% were African American, and the remainder were from other ethnic backgrounds. The three most common mechanisms of injury were motor vehicle crashes (29%), motorcycle/all-terrain vehicle crashes (19%), and falls (13%). Dr. deRoon-Cassini reported that administration of the ITSS within 4 days of injury demonstrated a 75% sensitivity for identifying the risk for PTSD and depression, a 94% specificity for PTSD, and a 96% specificity for depression, with a cutoff score of 2 out of 5 for both subscales based on a receiver operating characteristic (ROC) curve analysis.
One month following administration of the ITSS, 20% of patients were diagnosed with depression and 29% were diagnosed with PTSD. Of those diagnosed with PTSD, 55% met criteria for concomitant depression “so we are seeing a high comorbidity between PTSD and depression, which is consistent with the medical literature,” she said.
“The ITSS represents a brief way that we can screen for PTSD and depression within a trauma system,” Dr. deRoon-Cassini said. “At our institution, social workers administer the tool. They have a flow sheet in our EMR system where they enter the responses. If someone screens positive, a best practice recommendation is put into the patient’s chart, which gets funneled to a trauma psychology consult. On the treatment side we try to intervene by triaging the severity of the current distress the person is experiencing, past comorbidities, and past trauma histories. From there we decide whether to do a brief intervention or more intensive evidence-based interventions for PTSD or depression together or separately.”
The study was funded by a grant from the Medical College of Wisconsin. Coauthors included Joshua Hunt, PhD, of the Medical College of Wisconsin, Milwaukee; Ann Marie Warren, PhD, of Baylor Medical Center, Dallas; and Karen Brasel, MD, FACS, of Oregon Health & Science University, Portland. Dr. deRoon-Cassini reported having no financial disclosures.
WAIKOLOA, HAWAII – A new nine-item tool known as the Injured Trauma Survivor Screen demonstrated strong sensitivity and specificity for predicting posttraumatic stress disorder and depression in trauma patients.
At the annual meeting of the American Association for the Surgery of Trauma, Terri deRoon-Cassini, PhD, said that the rates of PTSD among trauma patients range from 10% to 42%, depending on the type of injury sustained. “There is significant life impairment, including an increased risk for suicide and an increased risk for morbidity and mortality,” said Dr. deRoon-Cassini, a clinical psychologist and associate professor with the division of trauma and critical care at the Medical College of Wisconsin, Milwaukee.
The ACS Committee on Trauma currently recommends PTSD screening by trauma centers, including the 20-item PTSD Checklist and the nine-item PHD-9 for depression. However, these symptom-based screens were not validated in hospitalized trauma patients. “This becomes important, because according to the symptom trajectory of PTSD after trauma, about 22% of people experience chronic disease and about 16%-18% of people who have symptoms at baseline do not translate to symptoms by 6 months, so screening with a symptom-based measure isn’t always the best route,” she said.
In an effort to create a brief screening tool to identify those at risk for PTSD and depression following traumatic injury, Dr. deRoon-Cassini and her associates scoured existing medical literature on the topic to review risk factors and created an item pool of questions based on those risk factors. They came up with 47 items and statistically “funneled out the items to create the most parsimonious model predicting who goes on to develop PTSD and depression separately,” she explained. They then created the Injured Trauma Survivor Screen (ITSS), a nine-item list of yes/no questions that takes about 5 minutes to administer: five items for PTSD and five items for depression, with one item that overlaps. The five ITSS PTSD questions are:
• Did you think you were going to die? (risk factor being perceived life threat; odds ratio 6.32).
• Do you think this was done to you intentionally? (risk factor being intentionality; OR, 4.24).
• Have you felt more restless, tense, or jumpy than usual? (risk factor being assessment of arousal; OR, 5.31).
• Have you found yourself unable to stop worrying? (risk factor being worry/rumination; OR, 4.49).
• Do you find yourself thinking that the world is unsafe and that people are not to be trusted? (risk factor being negative alterations in cognition; OR, 5.52).
The five ITSS depression questions are:
• Have you ever taken medication for, or been given a mental health diagnosis? (risk factor being preexisting psychopathology; OR, 10.58).
• Has there ever been a time in your life you have been bothered by feeling down or hopeless or lost all interest in things you usually enjoyed for more than 2 weeks? (risk factor being premorbid depression; OR, 3.78).
• Did you think you were going to die? (risk factor being perceived life threat; OR, 9.69).
• Have you felt emotionally detached from your loved ones? (risk factor being negative alteration in mood; OR, 8.03).
• Do you find yourself crying and are unsure why? (risk factor being mood/depression; OR, 9.18).
The researchers administered the survey to 139 patients at two trauma centers. More than half (69%) were male, 48% were white, 40% were African American, and the remainder were from other ethnic backgrounds. The three most common mechanisms of injury were motor vehicle crashes (29%), motorcycle/all-terrain vehicle crashes (19%), and falls (13%). Dr. deRoon-Cassini reported that administration of the ITSS within 4 days of injury demonstrated a 75% sensitivity for identifying the risk for PTSD and depression, a 94% specificity for PTSD, and a 96% specificity for depression, with a cutoff score of 2 out of 5 for both subscales based on a receiver operating characteristic (ROC) curve analysis.
One month following administration of the ITSS, 20% of patients were diagnosed with depression and 29% were diagnosed with PTSD. Of those diagnosed with PTSD, 55% met criteria for concomitant depression “so we are seeing a high comorbidity between PTSD and depression, which is consistent with the medical literature,” she said.
“The ITSS represents a brief way that we can screen for PTSD and depression within a trauma system,” Dr. deRoon-Cassini said. “At our institution, social workers administer the tool. They have a flow sheet in our EMR system where they enter the responses. If someone screens positive, a best practice recommendation is put into the patient’s chart, which gets funneled to a trauma psychology consult. On the treatment side we try to intervene by triaging the severity of the current distress the person is experiencing, past comorbidities, and past trauma histories. From there we decide whether to do a brief intervention or more intensive evidence-based interventions for PTSD or depression together or separately.”
The study was funded by a grant from the Medical College of Wisconsin. Coauthors included Joshua Hunt, PhD, of the Medical College of Wisconsin, Milwaukee; Ann Marie Warren, PhD, of Baylor Medical Center, Dallas; and Karen Brasel, MD, FACS, of Oregon Health & Science University, Portland. Dr. deRoon-Cassini reported having no financial disclosures.
Key clinical point:
Major finding: Administration of the Injured Trauma Survivor Screen (ITSS) within 4 days of injury demonstrated a 75% sensitivity for identifying the risk for PTSD and depression, a 94% specificity for PTSD, and a 96% specificity for depression.
Data source: An analysis of 139 patients from two trauma centers who completed the ITSS.
Disclosures: The study was funded by a grant from the Medical College of Wisconsin. Dr. deRoon-Cassini reported having no financial disclosures.
VIDEO: What will be the NIMH’s focus under Dr. Joshua Gordon?
NEW YORK – “Most clinicians probably don’t have problems identifying patients who are depressed and giving them a trial of an antidepressant or a second antidepressant, but where do they run into stumbling blocks?” That’s a question Joshua A. Gordon, MD, PhD, the new director of the National Institute of Mental Health, said he is pondering as he steps into his new role.
Both a practicing clinical psychiatrist and a neuroscientist with a lab chiefly dedicated to optogenetics, Dr. Gordon shared his thoughts about what the priorities of the world’s largest mental health research institute should be, and how to balance immediate patient needs with the development of future interventions.
Conducted in New York City, where Dr. Gordon saw patients, maintained a lab, and was an associate professor of psychiatry at Columbia University for nearly 2 decades, this is the last installment in a series of interviews.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
NEW YORK – “Most clinicians probably don’t have problems identifying patients who are depressed and giving them a trial of an antidepressant or a second antidepressant, but where do they run into stumbling blocks?” That’s a question Joshua A. Gordon, MD, PhD, the new director of the National Institute of Mental Health, said he is pondering as he steps into his new role.
Both a practicing clinical psychiatrist and a neuroscientist with a lab chiefly dedicated to optogenetics, Dr. Gordon shared his thoughts about what the priorities of the world’s largest mental health research institute should be, and how to balance immediate patient needs with the development of future interventions.
Conducted in New York City, where Dr. Gordon saw patients, maintained a lab, and was an associate professor of psychiatry at Columbia University for nearly 2 decades, this is the last installment in a series of interviews.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
NEW YORK – “Most clinicians probably don’t have problems identifying patients who are depressed and giving them a trial of an antidepressant or a second antidepressant, but where do they run into stumbling blocks?” That’s a question Joshua A. Gordon, MD, PhD, the new director of the National Institute of Mental Health, said he is pondering as he steps into his new role.
Both a practicing clinical psychiatrist and a neuroscientist with a lab chiefly dedicated to optogenetics, Dr. Gordon shared his thoughts about what the priorities of the world’s largest mental health research institute should be, and how to balance immediate patient needs with the development of future interventions.
Conducted in New York City, where Dr. Gordon saw patients, maintained a lab, and was an associate professor of psychiatry at Columbia University for nearly 2 decades, this is the last installment in a series of interviews.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
VIDEO: New NIMH director talks ethics, optogenetics, novel treatments for depression
NEW YORK – Will it ever be possible to trace the neuronal pathways of specific mental states as they speed through our brains? Hear Joshua A. Gordon, MD, PhD, the National Institute of Mental Health’s new director, share his thoughts on just such a technology in an interview recorded just days before he assumed his new role at the world’s largest mental health research organization.
In the interview, Dr. Gordon also addresses whether the use of “optogenetics” – a novel therapy developed by neuroscientists that, if it works, promises to track mental disorders such as anxiety or depression – creates ethical dilemmas when deciding whether these disorders should be turned “on” or “off.”
“When I treat patients, I treat them because they are overwhelmed with depression, or because they’re hearing voices that are scary or ruining their lives, or because they have intractable anxiety,” Dr. Gordon said. “To relieve those symptoms, there is no ethical dilemma in my mind.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
NEW YORK – Will it ever be possible to trace the neuronal pathways of specific mental states as they speed through our brains? Hear Joshua A. Gordon, MD, PhD, the National Institute of Mental Health’s new director, share his thoughts on just such a technology in an interview recorded just days before he assumed his new role at the world’s largest mental health research organization.
In the interview, Dr. Gordon also addresses whether the use of “optogenetics” – a novel therapy developed by neuroscientists that, if it works, promises to track mental disorders such as anxiety or depression – creates ethical dilemmas when deciding whether these disorders should be turned “on” or “off.”
“When I treat patients, I treat them because they are overwhelmed with depression, or because they’re hearing voices that are scary or ruining their lives, or because they have intractable anxiety,” Dr. Gordon said. “To relieve those symptoms, there is no ethical dilemma in my mind.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
NEW YORK – Will it ever be possible to trace the neuronal pathways of specific mental states as they speed through our brains? Hear Joshua A. Gordon, MD, PhD, the National Institute of Mental Health’s new director, share his thoughts on just such a technology in an interview recorded just days before he assumed his new role at the world’s largest mental health research organization.
In the interview, Dr. Gordon also addresses whether the use of “optogenetics” – a novel therapy developed by neuroscientists that, if it works, promises to track mental disorders such as anxiety or depression – creates ethical dilemmas when deciding whether these disorders should be turned “on” or “off.”
“When I treat patients, I treat them because they are overwhelmed with depression, or because they’re hearing voices that are scary or ruining their lives, or because they have intractable anxiety,” Dr. Gordon said. “To relieve those symptoms, there is no ethical dilemma in my mind.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
Update on argan oil
• Used traditionally in Northwest Africa for its cosmetic, bactericidal, and fungicidal activity.
• Rich in vitamin E, oleic acid, and linoleic acid, which are believed to contribute to the perceived cutaneous benefits of this vegetable oil.
• Reputed to impart antiacne, antisebum, antiaging, moisturizing, and wound-healing activity, but clinical evidence is sparse.
• In a small study, the nightly topical application of argan oil resulted in a moisturizing effect, and in statistically significant decreases in transepidermal water loss and increases in the water content of the epidermis.
For more than 800 years, native Moroccans and explorers in the region have cited the health benefits of the topical use or consumption of argan oil.1 The oil, derived from the fruit of Argania spinosa, is a slow-growing tree native to the arid climate of Southwestern Morocco2-4 as well as the Algerian province of Tindouf in the Western Mediterranean area.5 For many years, it was primarily the populations of the Essaouira and Souss-Massa-Draa regions of Morocco that benefited from the production and use of argan oil.6 Largely through the efforts of the Moroccan government, as well as cooperating nongovernmental organizations and private entities, argan oil is now also a well-established ingredient on the edible oil as well as cosmetic oil markets throughout the world.6
The vitamin E–rich oil has a reputation for imparting antiaging, hydrating, and antioxidant activity to the skin and ameliorating conditions such as acne, eczema, psoriasis, wrinkles, and xerosis,12 and, in fact, has been used to treat these conditions as well as dry hair,3,13 hair loss, skin inflammation, and joint pain.3 This column will focus on the topical uses of this botanical that has been dubbed “liquid gold.”12
Chemistry
Oleic acid, an omega-9 monounsaturated fatty acid, is abundant in argan oil (43%-49%) and has been found to act as a penetration enhancer by disturbing the skin barrier.14,15 Linoleic acid, an omega-6 polyunsaturated fatty acid, found in concentrations of 29%-36% in the oil, is integral in the biosynthesis of inflammatory prostaglandins through the arachidonic acid pathway.4,16 The presence of linoleic acid may help prevent or mitigate inflammation. Linoleic acid is also a component of ceramide 1 linoleate, which is diminished in dry skin. Topical application of linoleic acid can raise ceramide 1 linoleate levels in the skin, thus reducing xerosis.17 Argan oil also contains the saturated fatty acids palmitic acid (11%-15%) and stearic acid (4%-7%).2
Though argan oil is mainly composed of unsaturated fatty acids (80%),1,18,19 the unsaponifiable fraction (1%) is replete with antioxidants, including sterols, saponins, and polyphenols.4,19 The polyphenolic constituents, primarily gamma-tocopherol, which is considered the most efficient among the tocopherols at scavenging free radicals, are thought to account for the antioxidant effects of argan oil.1,2,18,20,21
Topical uses
Unroasted kernels are used to produce cosmetic-grade argan oil, which is used in moisturizing creams, body lotions, and shampoos.2 Although argan oil contains components that have antioxidant and anti-inflammatory features and there are many patents on the use of argan oil in skin care, there is a dearth of published research studies looking at the effect of argan oil–containing skin care products on aging, inflamed, or dry skin. A study by Dobrev evaluated the efficacy of a sebum control cream composed of saw palmetto extract, sesame seeds, and argan oil applied twice daily to the face over a period of 4 weeks in 20 healthy volunteers, 16 with oily skin and 4 with combination skin. All volunteers tolerated the product. A visible sebum-regulating or antisebum efficacy was observed in 95% of the subjects. Clinical evaluation scores and casual sebum levels decreased significantly after 1 month of treatment. Dobrev concluded that this argan oil-containing formulation was efficacious in lessening the greasiness and improving the appearance of oily facial skin.22
Early in 2015, Boucetta et al. reported on their study of the effects on skin elasticity of the daily application or consumption of argan oil in 60 postmenopausal women. During a 60-day period, the treatment group of 30 subjects consumed dietary argan oil; the 30 members in the control group received olive oil. Both groups also applied topical argan oil to the left volar forearm. Skin parameters, including gross skin elasticity, net elasticity, and biologic elasticity, improved significantly with both oral and topical treatments. The researchers concluded that argan oil use confers an antiaging effect to the skin through enhanced elasticity.24 Boucetta and another team previously showed that daily consumption or topical application of argan oil in postmenopausal women yielded significant reductions in transepidermal water loss and significant increases in epidermal water content, suggesting that the botanical agent ameliorates skin hydration by reviving barrier function and preserving the water-holding capacity.25 The same team also demonstrated in 30 healthy postmenopausal women that the nightly topical application of argan oil over a 2-month period yielded a moisturizing effect, with statistically significant reductions in transepidermal water loss and statistically significant increases in the water content of the epidermis observed.26
As a cosmetic agent, argan oil, which is popular in France, Japan, and North America, is touted for hydrating and revitalizing the skin, treating acne, and imparting shine to the hair. The therapeutic activities of topical argan oil are reputed to be antiacne, antisebum, antiaging, moisturizing, and wound healing, but such claims are based on traditional uses with only a small body of supportive clinical evidence.2,27
Generally, argan oil prices are as high as $40/100 mL in the European, Japanese, and American markets.27 Topical argan oil has been characterized as having a brief shelf-life of approximately 3-4 months.2,28 A 2014 report on a 1-year study of the oxidative stability of cosmetic argan oil by Gharby et al. found that argan oil quality remains satisfactory when stored at 25° C and protected from sunlight, but storage should not exceed 6 months to meet industrial standards. A rapid loss of quality was seen when argan oil was stored at 40° C.29
Conclusion
Although clinical research data on argan oil are limited, its traditional uses and inclusion in novel cosmetic products suggest that further study is warranted. Randomized controlled trials are needed to elucidate cutaneous benefits, if any, from this rare botanical.
1. J Pharm Pharmacol. 2010 Dec;62(12):1669-75.
2. Altern Med Rev. 2011 Sep;16(3):275-9.
3. J Ethnopharmacol. 1999 Oct;67(1):7-14.
4. Pharmacol Res. 2006 Jul;54(1):1-5.
5. Nutr Rev. 2012 May;70(5):266-79.
6. Eur J Lipid Sci Technol. 2014 Oct;116(10):1316-21.
7. Ann Nutr Metab. 2005 May-Jun;49(3):196-201.
8. Nutr Metab Cardiovasc Dis. 2005 Oct;15(5):352-60.
9. Evid Based Complement Alternat Med. 2006 Sep;3(3):317-27.
10. Cancer Invest. 2006 Oct;24(6):588-92.
11. Cancer Detect Prev. 2007;31(1):64-9.
12. “Liquid Gold in Morocco,” by Amy Larocca, The New York Times, Nov. 18, 2007.
13. Phytomedicine. 2010 Feb;17(2):157-60.
14. J Control Release. 1995;37(3):299-306.
15. Thermochimica Acta. 1997 Jun;293:77-85.
16. Prostaglandins Leukot Essent Fatty Acids. 1995 Jun;52(6):387-91.
17. Int J Cosmet Sci. 1996 Feb;18(1):1-12.
18. Crit Rev Food Sci Nutr. 2010 May;50(5):473-7.
19. Eur J Cancer Prev. 2003 Feb;12(1):67-75.
20. Fitoterapia. 2008 Jul;79(5):337-44.
21. Am J Clin Nutr. 2001 Dec;74(6):714-22.
22. J Cosmet Dermatol. 2007;6(2):113-8.
23. Int J Nanomedicine. 2014 Aug 11;9:3855-64.
24. Clin Interv Aging. 2015 Jan 30;10:339-49.
25. Prz Menopauzalny. 2014 Oct;13(5):280-8.
26. Skin Res Technol. 2013;19:356-7.
27. Inflamm Allergy Drug Targets. 2014;13(3):168-76.
28. Nat Prod Commun. 2010 Nov;5(11):1799-802.
29. J Cosmet Sci. 2014 Mar-Apr;65(2):81-7.
Dr. Baumann is the CEO of Baumann Cosmetic & Research Institute in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. She is the author of “Cosmetic Dermatology: Principles and Practice” (New York: McGraw Hill, 2002), and a book for consumers, “The Skin Type Solution,” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients” (McGraw Hill) was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also develops and owns the Baumann Skin Type Solution skin typing solutions and related products.
• Used traditionally in Northwest Africa for its cosmetic, bactericidal, and fungicidal activity.
• Rich in vitamin E, oleic acid, and linoleic acid, which are believed to contribute to the perceived cutaneous benefits of this vegetable oil.
• Reputed to impart antiacne, antisebum, antiaging, moisturizing, and wound-healing activity, but clinical evidence is sparse.
• In a small study, the nightly topical application of argan oil resulted in a moisturizing effect, and in statistically significant decreases in transepidermal water loss and increases in the water content of the epidermis.
For more than 800 years, native Moroccans and explorers in the region have cited the health benefits of the topical use or consumption of argan oil.1 The oil, derived from the fruit of Argania spinosa, is a slow-growing tree native to the arid climate of Southwestern Morocco2-4 as well as the Algerian province of Tindouf in the Western Mediterranean area.5 For many years, it was primarily the populations of the Essaouira and Souss-Massa-Draa regions of Morocco that benefited from the production and use of argan oil.6 Largely through the efforts of the Moroccan government, as well as cooperating nongovernmental organizations and private entities, argan oil is now also a well-established ingredient on the edible oil as well as cosmetic oil markets throughout the world.6
The vitamin E–rich oil has a reputation for imparting antiaging, hydrating, and antioxidant activity to the skin and ameliorating conditions such as acne, eczema, psoriasis, wrinkles, and xerosis,12 and, in fact, has been used to treat these conditions as well as dry hair,3,13 hair loss, skin inflammation, and joint pain.3 This column will focus on the topical uses of this botanical that has been dubbed “liquid gold.”12
Chemistry
Oleic acid, an omega-9 monounsaturated fatty acid, is abundant in argan oil (43%-49%) and has been found to act as a penetration enhancer by disturbing the skin barrier.14,15 Linoleic acid, an omega-6 polyunsaturated fatty acid, found in concentrations of 29%-36% in the oil, is integral in the biosynthesis of inflammatory prostaglandins through the arachidonic acid pathway.4,16 The presence of linoleic acid may help prevent or mitigate inflammation. Linoleic acid is also a component of ceramide 1 linoleate, which is diminished in dry skin. Topical application of linoleic acid can raise ceramide 1 linoleate levels in the skin, thus reducing xerosis.17 Argan oil also contains the saturated fatty acids palmitic acid (11%-15%) and stearic acid (4%-7%).2
Though argan oil is mainly composed of unsaturated fatty acids (80%),1,18,19 the unsaponifiable fraction (1%) is replete with antioxidants, including sterols, saponins, and polyphenols.4,19 The polyphenolic constituents, primarily gamma-tocopherol, which is considered the most efficient among the tocopherols at scavenging free radicals, are thought to account for the antioxidant effects of argan oil.1,2,18,20,21
Topical uses
Unroasted kernels are used to produce cosmetic-grade argan oil, which is used in moisturizing creams, body lotions, and shampoos.2 Although argan oil contains components that have antioxidant and anti-inflammatory features and there are many patents on the use of argan oil in skin care, there is a dearth of published research studies looking at the effect of argan oil–containing skin care products on aging, inflamed, or dry skin. A study by Dobrev evaluated the efficacy of a sebum control cream composed of saw palmetto extract, sesame seeds, and argan oil applied twice daily to the face over a period of 4 weeks in 20 healthy volunteers, 16 with oily skin and 4 with combination skin. All volunteers tolerated the product. A visible sebum-regulating or antisebum efficacy was observed in 95% of the subjects. Clinical evaluation scores and casual sebum levels decreased significantly after 1 month of treatment. Dobrev concluded that this argan oil-containing formulation was efficacious in lessening the greasiness and improving the appearance of oily facial skin.22
Early in 2015, Boucetta et al. reported on their study of the effects on skin elasticity of the daily application or consumption of argan oil in 60 postmenopausal women. During a 60-day period, the treatment group of 30 subjects consumed dietary argan oil; the 30 members in the control group received olive oil. Both groups also applied topical argan oil to the left volar forearm. Skin parameters, including gross skin elasticity, net elasticity, and biologic elasticity, improved significantly with both oral and topical treatments. The researchers concluded that argan oil use confers an antiaging effect to the skin through enhanced elasticity.24 Boucetta and another team previously showed that daily consumption or topical application of argan oil in postmenopausal women yielded significant reductions in transepidermal water loss and significant increases in epidermal water content, suggesting that the botanical agent ameliorates skin hydration by reviving barrier function and preserving the water-holding capacity.25 The same team also demonstrated in 30 healthy postmenopausal women that the nightly topical application of argan oil over a 2-month period yielded a moisturizing effect, with statistically significant reductions in transepidermal water loss and statistically significant increases in the water content of the epidermis observed.26
As a cosmetic agent, argan oil, which is popular in France, Japan, and North America, is touted for hydrating and revitalizing the skin, treating acne, and imparting shine to the hair. The therapeutic activities of topical argan oil are reputed to be antiacne, antisebum, antiaging, moisturizing, and wound healing, but such claims are based on traditional uses with only a small body of supportive clinical evidence.2,27
Generally, argan oil prices are as high as $40/100 mL in the European, Japanese, and American markets.27 Topical argan oil has been characterized as having a brief shelf-life of approximately 3-4 months.2,28 A 2014 report on a 1-year study of the oxidative stability of cosmetic argan oil by Gharby et al. found that argan oil quality remains satisfactory when stored at 25° C and protected from sunlight, but storage should not exceed 6 months to meet industrial standards. A rapid loss of quality was seen when argan oil was stored at 40° C.29
Conclusion
Although clinical research data on argan oil are limited, its traditional uses and inclusion in novel cosmetic products suggest that further study is warranted. Randomized controlled trials are needed to elucidate cutaneous benefits, if any, from this rare botanical.
1. J Pharm Pharmacol. 2010 Dec;62(12):1669-75.
2. Altern Med Rev. 2011 Sep;16(3):275-9.
3. J Ethnopharmacol. 1999 Oct;67(1):7-14.
4. Pharmacol Res. 2006 Jul;54(1):1-5.
5. Nutr Rev. 2012 May;70(5):266-79.
6. Eur J Lipid Sci Technol. 2014 Oct;116(10):1316-21.
7. Ann Nutr Metab. 2005 May-Jun;49(3):196-201.
8. Nutr Metab Cardiovasc Dis. 2005 Oct;15(5):352-60.
9. Evid Based Complement Alternat Med. 2006 Sep;3(3):317-27.
10. Cancer Invest. 2006 Oct;24(6):588-92.
11. Cancer Detect Prev. 2007;31(1):64-9.
12. “Liquid Gold in Morocco,” by Amy Larocca, The New York Times, Nov. 18, 2007.
13. Phytomedicine. 2010 Feb;17(2):157-60.
14. J Control Release. 1995;37(3):299-306.
15. Thermochimica Acta. 1997 Jun;293:77-85.
16. Prostaglandins Leukot Essent Fatty Acids. 1995 Jun;52(6):387-91.
17. Int J Cosmet Sci. 1996 Feb;18(1):1-12.
18. Crit Rev Food Sci Nutr. 2010 May;50(5):473-7.
19. Eur J Cancer Prev. 2003 Feb;12(1):67-75.
20. Fitoterapia. 2008 Jul;79(5):337-44.
21. Am J Clin Nutr. 2001 Dec;74(6):714-22.
22. J Cosmet Dermatol. 2007;6(2):113-8.
23. Int J Nanomedicine. 2014 Aug 11;9:3855-64.
24. Clin Interv Aging. 2015 Jan 30;10:339-49.
25. Prz Menopauzalny. 2014 Oct;13(5):280-8.
26. Skin Res Technol. 2013;19:356-7.
27. Inflamm Allergy Drug Targets. 2014;13(3):168-76.
28. Nat Prod Commun. 2010 Nov;5(11):1799-802.
29. J Cosmet Sci. 2014 Mar-Apr;65(2):81-7.
Dr. Baumann is the CEO of Baumann Cosmetic & Research Institute in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. She is the author of “Cosmetic Dermatology: Principles and Practice” (New York: McGraw Hill, 2002), and a book for consumers, “The Skin Type Solution,” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients” (McGraw Hill) was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also develops and owns the Baumann Skin Type Solution skin typing solutions and related products.
• Used traditionally in Northwest Africa for its cosmetic, bactericidal, and fungicidal activity.
• Rich in vitamin E, oleic acid, and linoleic acid, which are believed to contribute to the perceived cutaneous benefits of this vegetable oil.
• Reputed to impart antiacne, antisebum, antiaging, moisturizing, and wound-healing activity, but clinical evidence is sparse.
• In a small study, the nightly topical application of argan oil resulted in a moisturizing effect, and in statistically significant decreases in transepidermal water loss and increases in the water content of the epidermis.
For more than 800 years, native Moroccans and explorers in the region have cited the health benefits of the topical use or consumption of argan oil.1 The oil, derived from the fruit of Argania spinosa, is a slow-growing tree native to the arid climate of Southwestern Morocco2-4 as well as the Algerian province of Tindouf in the Western Mediterranean area.5 For many years, it was primarily the populations of the Essaouira and Souss-Massa-Draa regions of Morocco that benefited from the production and use of argan oil.6 Largely through the efforts of the Moroccan government, as well as cooperating nongovernmental organizations and private entities, argan oil is now also a well-established ingredient on the edible oil as well as cosmetic oil markets throughout the world.6
The vitamin E–rich oil has a reputation for imparting antiaging, hydrating, and antioxidant activity to the skin and ameliorating conditions such as acne, eczema, psoriasis, wrinkles, and xerosis,12 and, in fact, has been used to treat these conditions as well as dry hair,3,13 hair loss, skin inflammation, and joint pain.3 This column will focus on the topical uses of this botanical that has been dubbed “liquid gold.”12
Chemistry
Oleic acid, an omega-9 monounsaturated fatty acid, is abundant in argan oil (43%-49%) and has been found to act as a penetration enhancer by disturbing the skin barrier.14,15 Linoleic acid, an omega-6 polyunsaturated fatty acid, found in concentrations of 29%-36% in the oil, is integral in the biosynthesis of inflammatory prostaglandins through the arachidonic acid pathway.4,16 The presence of linoleic acid may help prevent or mitigate inflammation. Linoleic acid is also a component of ceramide 1 linoleate, which is diminished in dry skin. Topical application of linoleic acid can raise ceramide 1 linoleate levels in the skin, thus reducing xerosis.17 Argan oil also contains the saturated fatty acids palmitic acid (11%-15%) and stearic acid (4%-7%).2
Though argan oil is mainly composed of unsaturated fatty acids (80%),1,18,19 the unsaponifiable fraction (1%) is replete with antioxidants, including sterols, saponins, and polyphenols.4,19 The polyphenolic constituents, primarily gamma-tocopherol, which is considered the most efficient among the tocopherols at scavenging free radicals, are thought to account for the antioxidant effects of argan oil.1,2,18,20,21
Topical uses
Unroasted kernels are used to produce cosmetic-grade argan oil, which is used in moisturizing creams, body lotions, and shampoos.2 Although argan oil contains components that have antioxidant and anti-inflammatory features and there are many patents on the use of argan oil in skin care, there is a dearth of published research studies looking at the effect of argan oil–containing skin care products on aging, inflamed, or dry skin. A study by Dobrev evaluated the efficacy of a sebum control cream composed of saw palmetto extract, sesame seeds, and argan oil applied twice daily to the face over a period of 4 weeks in 20 healthy volunteers, 16 with oily skin and 4 with combination skin. All volunteers tolerated the product. A visible sebum-regulating or antisebum efficacy was observed in 95% of the subjects. Clinical evaluation scores and casual sebum levels decreased significantly after 1 month of treatment. Dobrev concluded that this argan oil-containing formulation was efficacious in lessening the greasiness and improving the appearance of oily facial skin.22
Early in 2015, Boucetta et al. reported on their study of the effects on skin elasticity of the daily application or consumption of argan oil in 60 postmenopausal women. During a 60-day period, the treatment group of 30 subjects consumed dietary argan oil; the 30 members in the control group received olive oil. Both groups also applied topical argan oil to the left volar forearm. Skin parameters, including gross skin elasticity, net elasticity, and biologic elasticity, improved significantly with both oral and topical treatments. The researchers concluded that argan oil use confers an antiaging effect to the skin through enhanced elasticity.24 Boucetta and another team previously showed that daily consumption or topical application of argan oil in postmenopausal women yielded significant reductions in transepidermal water loss and significant increases in epidermal water content, suggesting that the botanical agent ameliorates skin hydration by reviving barrier function and preserving the water-holding capacity.25 The same team also demonstrated in 30 healthy postmenopausal women that the nightly topical application of argan oil over a 2-month period yielded a moisturizing effect, with statistically significant reductions in transepidermal water loss and statistically significant increases in the water content of the epidermis observed.26
As a cosmetic agent, argan oil, which is popular in France, Japan, and North America, is touted for hydrating and revitalizing the skin, treating acne, and imparting shine to the hair. The therapeutic activities of topical argan oil are reputed to be antiacne, antisebum, antiaging, moisturizing, and wound healing, but such claims are based on traditional uses with only a small body of supportive clinical evidence.2,27
Generally, argan oil prices are as high as $40/100 mL in the European, Japanese, and American markets.27 Topical argan oil has been characterized as having a brief shelf-life of approximately 3-4 months.2,28 A 2014 report on a 1-year study of the oxidative stability of cosmetic argan oil by Gharby et al. found that argan oil quality remains satisfactory when stored at 25° C and protected from sunlight, but storage should not exceed 6 months to meet industrial standards. A rapid loss of quality was seen when argan oil was stored at 40° C.29
Conclusion
Although clinical research data on argan oil are limited, its traditional uses and inclusion in novel cosmetic products suggest that further study is warranted. Randomized controlled trials are needed to elucidate cutaneous benefits, if any, from this rare botanical.
1. J Pharm Pharmacol. 2010 Dec;62(12):1669-75.
2. Altern Med Rev. 2011 Sep;16(3):275-9.
3. J Ethnopharmacol. 1999 Oct;67(1):7-14.
4. Pharmacol Res. 2006 Jul;54(1):1-5.
5. Nutr Rev. 2012 May;70(5):266-79.
6. Eur J Lipid Sci Technol. 2014 Oct;116(10):1316-21.
7. Ann Nutr Metab. 2005 May-Jun;49(3):196-201.
8. Nutr Metab Cardiovasc Dis. 2005 Oct;15(5):352-60.
9. Evid Based Complement Alternat Med. 2006 Sep;3(3):317-27.
10. Cancer Invest. 2006 Oct;24(6):588-92.
11. Cancer Detect Prev. 2007;31(1):64-9.
12. “Liquid Gold in Morocco,” by Amy Larocca, The New York Times, Nov. 18, 2007.
13. Phytomedicine. 2010 Feb;17(2):157-60.
14. J Control Release. 1995;37(3):299-306.
15. Thermochimica Acta. 1997 Jun;293:77-85.
16. Prostaglandins Leukot Essent Fatty Acids. 1995 Jun;52(6):387-91.
17. Int J Cosmet Sci. 1996 Feb;18(1):1-12.
18. Crit Rev Food Sci Nutr. 2010 May;50(5):473-7.
19. Eur J Cancer Prev. 2003 Feb;12(1):67-75.
20. Fitoterapia. 2008 Jul;79(5):337-44.
21. Am J Clin Nutr. 2001 Dec;74(6):714-22.
22. J Cosmet Dermatol. 2007;6(2):113-8.
23. Int J Nanomedicine. 2014 Aug 11;9:3855-64.
24. Clin Interv Aging. 2015 Jan 30;10:339-49.
25. Prz Menopauzalny. 2014 Oct;13(5):280-8.
26. Skin Res Technol. 2013;19:356-7.
27. Inflamm Allergy Drug Targets. 2014;13(3):168-76.
28. Nat Prod Commun. 2010 Nov;5(11):1799-802.
29. J Cosmet Sci. 2014 Mar-Apr;65(2):81-7.
Dr. Baumann is the CEO of Baumann Cosmetic & Research Institute in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. She is the author of “Cosmetic Dermatology: Principles and Practice” (New York: McGraw Hill, 2002), and a book for consumers, “The Skin Type Solution,” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients” (McGraw Hill) was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also develops and owns the Baumann Skin Type Solution skin typing solutions and related products.
AHA: Midlife hypertension linked with cognitive impairment
Unchecked hypertension has “devastating” long-term implications for cognitive health, the American Heart Association concluded in a scientific statement.
“Hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology,” Costantino Iadecola, MD, of Weill Medical College of Cornell University, wrote online with his associates in Hypertension. There is especially strong evidence that hypertension in middle age leads to cognitive dysfunction later in life, although “the cognitive impact of late-life hypertension is less clear,” they said.
The AHA statement summarizes the current evidence on hypertension, cognitive impairment, and the cognitive effects of hypertension therapy. Observational studies linked hypertension to cumulative cerebrovascular damage over the course of life, but clinical trials did not clearly show that antihypertensive drugs can prevent or reverse cognitive decline, the authors reported. In lieu of making evidence-based recommendations, they emphasized “personalized treatment of hypertension, taking into account age, sex, APOE [apolipoprotein E] genotype, metabolic traits, [and] comorbidities” (Hypertension. 2016 Oct 10. doi: 10.1161/HYP.0000000000000053).
The authors wrote on behalf of the American Heart Association Councils on Hypertension, Clinical Cardiology, Cardiovascular Disease in the Young, Cardiovascular and Stroke Nursing, and Quality of Care and Outcomes Research, and Stroke. Dr. Iadecola and nine coauthors had no relevant financial disclosures. The remaining three coauthors disclosed research funding from the National Institutes of Health, Lilly, TauRX, and Biogen, and one of these coauthors also disclosed consulting or advisory board work for Lundbeck Pharmaceuticals and the Dominantly Inherited Alzheimer Network Trials Unit.
Unchecked hypertension has “devastating” long-term implications for cognitive health, the American Heart Association concluded in a scientific statement.
“Hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology,” Costantino Iadecola, MD, of Weill Medical College of Cornell University, wrote online with his associates in Hypertension. There is especially strong evidence that hypertension in middle age leads to cognitive dysfunction later in life, although “the cognitive impact of late-life hypertension is less clear,” they said.
The AHA statement summarizes the current evidence on hypertension, cognitive impairment, and the cognitive effects of hypertension therapy. Observational studies linked hypertension to cumulative cerebrovascular damage over the course of life, but clinical trials did not clearly show that antihypertensive drugs can prevent or reverse cognitive decline, the authors reported. In lieu of making evidence-based recommendations, they emphasized “personalized treatment of hypertension, taking into account age, sex, APOE [apolipoprotein E] genotype, metabolic traits, [and] comorbidities” (Hypertension. 2016 Oct 10. doi: 10.1161/HYP.0000000000000053).
The authors wrote on behalf of the American Heart Association Councils on Hypertension, Clinical Cardiology, Cardiovascular Disease in the Young, Cardiovascular and Stroke Nursing, and Quality of Care and Outcomes Research, and Stroke. Dr. Iadecola and nine coauthors had no relevant financial disclosures. The remaining three coauthors disclosed research funding from the National Institutes of Health, Lilly, TauRX, and Biogen, and one of these coauthors also disclosed consulting or advisory board work for Lundbeck Pharmaceuticals and the Dominantly Inherited Alzheimer Network Trials Unit.
Unchecked hypertension has “devastating” long-term implications for cognitive health, the American Heart Association concluded in a scientific statement.
“Hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology,” Costantino Iadecola, MD, of Weill Medical College of Cornell University, wrote online with his associates in Hypertension. There is especially strong evidence that hypertension in middle age leads to cognitive dysfunction later in life, although “the cognitive impact of late-life hypertension is less clear,” they said.
The AHA statement summarizes the current evidence on hypertension, cognitive impairment, and the cognitive effects of hypertension therapy. Observational studies linked hypertension to cumulative cerebrovascular damage over the course of life, but clinical trials did not clearly show that antihypertensive drugs can prevent or reverse cognitive decline, the authors reported. In lieu of making evidence-based recommendations, they emphasized “personalized treatment of hypertension, taking into account age, sex, APOE [apolipoprotein E] genotype, metabolic traits, [and] comorbidities” (Hypertension. 2016 Oct 10. doi: 10.1161/HYP.0000000000000053).
The authors wrote on behalf of the American Heart Association Councils on Hypertension, Clinical Cardiology, Cardiovascular Disease in the Young, Cardiovascular and Stroke Nursing, and Quality of Care and Outcomes Research, and Stroke. Dr. Iadecola and nine coauthors had no relevant financial disclosures. The remaining three coauthors disclosed research funding from the National Institutes of Health, Lilly, TauRX, and Biogen, and one of these coauthors also disclosed consulting or advisory board work for Lundbeck Pharmaceuticals and the Dominantly Inherited Alzheimer Network Trials Unit.
Benefits of lebrikizumab in asthma inconsistent
LONDON – Two large phase III trials with lebrikizumab, a monoclonal antibody that blocks the activity of interleukin-13 (IL-13), produced inconsistent evidence of benefit in patients with uncontrolled asthma, according to a presentation of both sets of data at the annual congress of the European Respiratory Society.
The two phase III studies compared lebrikizumab in doses of 37.5 mg and 125 mg to placebo, each administered subcutaneously every 4 weeks. The results were mixed not only for the primary endpoint, which was a reduction in the rate of exacerbations, but also for several secondary outcomes.
Evenly randomized into three treatment arms, 1,081 patients were enrolled in LAVOLTA I and 1,081 in LAVOLTA II. For entry, patients were required to have a forced expiratory volume in 1 second (FEV1) between 40% and 80% of predicted. Lebrikizumab was added on top of stable background therapy. For the efficacy analyses, patients were divided into those who were biomarker high, defined as having levels of periostin greater than 50 ng/mL or blood eosinophils greater than 300 mcg/L, or biomarker low, defined as having lower levels of periostin and blood eosinophils.
Over the 52-week study period in the biomarker high patients enrolled in LAVOLTA I, the rate of exacerbations was 51% lower among those randomized to the 37.5 mg dose (P less than .001) and 30% lower (P = .0232) among those randomized to the 125-mg dose relative to placebo. In the biomarker low group, a statistically significant 45% reduction in exacerbations was achieved with the 37.5 mg dose relative to placebo (P = .0318), but a 28% reduction in exacerbations, which was achieved in patients taking the 125-mg dose, was not statistically significant.
In the biomarker high patients enrolled in LAVOLTA II, both the 37.5-mg and the 125-mg doses reduced the rate of exacerbations by 26% relative to placebo, but neither reduction reached statistical significance. In the biomarker low patients, the 37.5-mg dose was associated with a 46% increase in exacerbations and the 125-mg dose was associated with a 6% increase in exacerbations relative to placebo.
In LAVOLTA I, lung function (as measured by FEV1) improved in biomarker high patients in both active treatment arms relative to placebo. The relative advantage of taking lebrikizumab was seen only in the biomarker low patients who took the 125-mg dose.
In LAVOLTA II, a similar advantage was observed in biomarker high patients who took both doses of lebrikizumab over biomarker high patients who took the placebo. There were no significant differences in outcomes observed between any treatment arms in the biomarker low group of LAVOLTA II.
Changes in other secondary endpoints were also inconsistent between the two studies. For example, the time to first exacerbation was significantly increased by lebrikizumab in LAVOLTA I but not in LAVOLTA II. Although use of rescue medications was significantly lower in patients receiving lebrikizumab in both studies, the rate of urgent health care utilization, such as emergency department visits, was lower in patients who took lebrikizumab in LAVOLTA 1, but not in those patients who too the drug in LAVOLTA II.
One consistency between the two studies’ outcomes was a lack of “meaningful improvements” having occurred in patients’ quality of life, as measured by the Asthma Quality of Life Questionnaire and the 5-item Asthma Control Questionnaire, according to Dr. Hanania.
The only difference in the occurrences of events associated with impaired immune function observed between any of the groups was a slight increase in the rate of herpes zoster among those treated with lebrikizumab relative to placebo (1.1% vs. 0.3%), Dr. Hanania reported. The only death that occurred in either study involved a patient in a placebo group. The rates of other side effects were comparable among patients in the active treatment and placebo groups.
An improvement in exacerbations would be consistent with the purported mechanism of lebrikizumab, because IL-13 is believed to induce expression of periostin, which, in turn, is thought to mediate bronchial hyper-responsiveness. In previously completed phase II trials, lebrikizumab was associated with a significant reduction in the rate of exacerbations over 24 weeks among patients with moderate to severe asthma (Thorax. 2015;80:748-56).
Asked in the discussion period whether the results of LAVOLTA I and II signaled the end of lebrikizumab studies in asthma control, Dr. Hanania deferred the question to Roche, which is developing this agent.
He noted that additional studies in a more select group of patients may be warranted and that lebrikizumab is still being evaluated for use in other lung diseases, such as idiopathic pulmonary fibrosis.
Dr. Hanania reports financial relationships with Forest, GlaxoSmithKline, Novartis, Pfizer, and Roche.
LONDON – Two large phase III trials with lebrikizumab, a monoclonal antibody that blocks the activity of interleukin-13 (IL-13), produced inconsistent evidence of benefit in patients with uncontrolled asthma, according to a presentation of both sets of data at the annual congress of the European Respiratory Society.
The two phase III studies compared lebrikizumab in doses of 37.5 mg and 125 mg to placebo, each administered subcutaneously every 4 weeks. The results were mixed not only for the primary endpoint, which was a reduction in the rate of exacerbations, but also for several secondary outcomes.
Evenly randomized into three treatment arms, 1,081 patients were enrolled in LAVOLTA I and 1,081 in LAVOLTA II. For entry, patients were required to have a forced expiratory volume in 1 second (FEV1) between 40% and 80% of predicted. Lebrikizumab was added on top of stable background therapy. For the efficacy analyses, patients were divided into those who were biomarker high, defined as having levels of periostin greater than 50 ng/mL or blood eosinophils greater than 300 mcg/L, or biomarker low, defined as having lower levels of periostin and blood eosinophils.
Over the 52-week study period in the biomarker high patients enrolled in LAVOLTA I, the rate of exacerbations was 51% lower among those randomized to the 37.5 mg dose (P less than .001) and 30% lower (P = .0232) among those randomized to the 125-mg dose relative to placebo. In the biomarker low group, a statistically significant 45% reduction in exacerbations was achieved with the 37.5 mg dose relative to placebo (P = .0318), but a 28% reduction in exacerbations, which was achieved in patients taking the 125-mg dose, was not statistically significant.
In the biomarker high patients enrolled in LAVOLTA II, both the 37.5-mg and the 125-mg doses reduced the rate of exacerbations by 26% relative to placebo, but neither reduction reached statistical significance. In the biomarker low patients, the 37.5-mg dose was associated with a 46% increase in exacerbations and the 125-mg dose was associated with a 6% increase in exacerbations relative to placebo.
In LAVOLTA I, lung function (as measured by FEV1) improved in biomarker high patients in both active treatment arms relative to placebo. The relative advantage of taking lebrikizumab was seen only in the biomarker low patients who took the 125-mg dose.
In LAVOLTA II, a similar advantage was observed in biomarker high patients who took both doses of lebrikizumab over biomarker high patients who took the placebo. There were no significant differences in outcomes observed between any treatment arms in the biomarker low group of LAVOLTA II.
Changes in other secondary endpoints were also inconsistent between the two studies. For example, the time to first exacerbation was significantly increased by lebrikizumab in LAVOLTA I but not in LAVOLTA II. Although use of rescue medications was significantly lower in patients receiving lebrikizumab in both studies, the rate of urgent health care utilization, such as emergency department visits, was lower in patients who took lebrikizumab in LAVOLTA 1, but not in those patients who too the drug in LAVOLTA II.
One consistency between the two studies’ outcomes was a lack of “meaningful improvements” having occurred in patients’ quality of life, as measured by the Asthma Quality of Life Questionnaire and the 5-item Asthma Control Questionnaire, according to Dr. Hanania.
The only difference in the occurrences of events associated with impaired immune function observed between any of the groups was a slight increase in the rate of herpes zoster among those treated with lebrikizumab relative to placebo (1.1% vs. 0.3%), Dr. Hanania reported. The only death that occurred in either study involved a patient in a placebo group. The rates of other side effects were comparable among patients in the active treatment and placebo groups.
An improvement in exacerbations would be consistent with the purported mechanism of lebrikizumab, because IL-13 is believed to induce expression of periostin, which, in turn, is thought to mediate bronchial hyper-responsiveness. In previously completed phase II trials, lebrikizumab was associated with a significant reduction in the rate of exacerbations over 24 weeks among patients with moderate to severe asthma (Thorax. 2015;80:748-56).
Asked in the discussion period whether the results of LAVOLTA I and II signaled the end of lebrikizumab studies in asthma control, Dr. Hanania deferred the question to Roche, which is developing this agent.
He noted that additional studies in a more select group of patients may be warranted and that lebrikizumab is still being evaluated for use in other lung diseases, such as idiopathic pulmonary fibrosis.
Dr. Hanania reports financial relationships with Forest, GlaxoSmithKline, Novartis, Pfizer, and Roche.
LONDON – Two large phase III trials with lebrikizumab, a monoclonal antibody that blocks the activity of interleukin-13 (IL-13), produced inconsistent evidence of benefit in patients with uncontrolled asthma, according to a presentation of both sets of data at the annual congress of the European Respiratory Society.
The two phase III studies compared lebrikizumab in doses of 37.5 mg and 125 mg to placebo, each administered subcutaneously every 4 weeks. The results were mixed not only for the primary endpoint, which was a reduction in the rate of exacerbations, but also for several secondary outcomes.
Evenly randomized into three treatment arms, 1,081 patients were enrolled in LAVOLTA I and 1,081 in LAVOLTA II. For entry, patients were required to have a forced expiratory volume in 1 second (FEV1) between 40% and 80% of predicted. Lebrikizumab was added on top of stable background therapy. For the efficacy analyses, patients were divided into those who were biomarker high, defined as having levels of periostin greater than 50 ng/mL or blood eosinophils greater than 300 mcg/L, or biomarker low, defined as having lower levels of periostin and blood eosinophils.
Over the 52-week study period in the biomarker high patients enrolled in LAVOLTA I, the rate of exacerbations was 51% lower among those randomized to the 37.5 mg dose (P less than .001) and 30% lower (P = .0232) among those randomized to the 125-mg dose relative to placebo. In the biomarker low group, a statistically significant 45% reduction in exacerbations was achieved with the 37.5 mg dose relative to placebo (P = .0318), but a 28% reduction in exacerbations, which was achieved in patients taking the 125-mg dose, was not statistically significant.
In the biomarker high patients enrolled in LAVOLTA II, both the 37.5-mg and the 125-mg doses reduced the rate of exacerbations by 26% relative to placebo, but neither reduction reached statistical significance. In the biomarker low patients, the 37.5-mg dose was associated with a 46% increase in exacerbations and the 125-mg dose was associated with a 6% increase in exacerbations relative to placebo.
In LAVOLTA I, lung function (as measured by FEV1) improved in biomarker high patients in both active treatment arms relative to placebo. The relative advantage of taking lebrikizumab was seen only in the biomarker low patients who took the 125-mg dose.
In LAVOLTA II, a similar advantage was observed in biomarker high patients who took both doses of lebrikizumab over biomarker high patients who took the placebo. There were no significant differences in outcomes observed between any treatment arms in the biomarker low group of LAVOLTA II.
Changes in other secondary endpoints were also inconsistent between the two studies. For example, the time to first exacerbation was significantly increased by lebrikizumab in LAVOLTA I but not in LAVOLTA II. Although use of rescue medications was significantly lower in patients receiving lebrikizumab in both studies, the rate of urgent health care utilization, such as emergency department visits, was lower in patients who took lebrikizumab in LAVOLTA 1, but not in those patients who too the drug in LAVOLTA II.
One consistency between the two studies’ outcomes was a lack of “meaningful improvements” having occurred in patients’ quality of life, as measured by the Asthma Quality of Life Questionnaire and the 5-item Asthma Control Questionnaire, according to Dr. Hanania.
The only difference in the occurrences of events associated with impaired immune function observed between any of the groups was a slight increase in the rate of herpes zoster among those treated with lebrikizumab relative to placebo (1.1% vs. 0.3%), Dr. Hanania reported. The only death that occurred in either study involved a patient in a placebo group. The rates of other side effects were comparable among patients in the active treatment and placebo groups.
An improvement in exacerbations would be consistent with the purported mechanism of lebrikizumab, because IL-13 is believed to induce expression of periostin, which, in turn, is thought to mediate bronchial hyper-responsiveness. In previously completed phase II trials, lebrikizumab was associated with a significant reduction in the rate of exacerbations over 24 weeks among patients with moderate to severe asthma (Thorax. 2015;80:748-56).
Asked in the discussion period whether the results of LAVOLTA I and II signaled the end of lebrikizumab studies in asthma control, Dr. Hanania deferred the question to Roche, which is developing this agent.
He noted that additional studies in a more select group of patients may be warranted and that lebrikizumab is still being evaluated for use in other lung diseases, such as idiopathic pulmonary fibrosis.
Dr. Hanania reports financial relationships with Forest, GlaxoSmithKline, Novartis, Pfizer, and Roche.
AT THE ERS CONGRESS 2016
Key clinical point: The primary efficacy endpoint was achieved in only one of two phase III trials of lebrikizumab for treatment of uncontrolled asthma.
Major finding: For lebrikizumab, which targets IL-13, the inconsistency of significant benefit clouds its future as an asthma treatment.
Data source: A placebo-controlled multicenter phase III program.
Disclosures: Dr. Hanania reports financial relationships with Forest, GlaxoSmithKline, Novartis, Pfizer, and Roche.
Patients with stage 1 NSCLC more likely to die of other causes in short term
Patients with stage 1 non–small cell lung cancer who underwent resection with intent to cure were more likely, over the short term, to die of other causes, investigators reported.
“Non–cancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Takashi Eguchi, MD, and his associates at Memorial Sloan Kettering Cancer Center, New York wrote (J Clin Oncol. 2016 Oct 10. doi: 10.1200/JCO.2016.69.0834).
“These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status, and help determine patients’ optimal treatment options.”
The study included 2,186 patients who underwent curative-intent resection of stage 1 non-small cell lung cancer at Memorial Sloan Kettering between 2000 and 2011. The cumulative 5-year lung cancer death rate was 10.4%, but rose with age from 7.5% among patients younger than 65 years to 13.2% among patients who were at least 75 years old. Cumulative 5-year rates of mortality not due to cancer were lower, at 5.3% overall, 1.8% in the youngest cohort, and 9% in the oldest cohort. But a competing risk analysis of the entire cohort showed that non–cancer-specific cumulative mortality was higher than mortality from lung cancer for up to 1.5 years after resection, the investigators found. Furthermore, patients who were at least 75 years old were more likely to die of causes other than cancer for up to 2.5 years after surgery.
In the multivariable analysis, low predicted postoperative diffusing capacity of lung for carbon monoxide (DCLO) independently predicted severe morbidity (P less than .001), 1-year mortality (P less than .001), and non–cancer-specific mortality (P less than .001), the researchers said. These findings reflect prior work linking low DCLO with obstructive, restrictive, and pulmonary vascular disease, chronic heart failure, and poor postoperative outcomes, they noted.
Senior author Prasad S. Adusumilli, MD, provided funding. Dr. Eguchi and Dr. Adusumilli had no relevant financial disclosures.
Patients with stage 1 non–small cell lung cancer who underwent resection with intent to cure were more likely, over the short term, to die of other causes, investigators reported.
“Non–cancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Takashi Eguchi, MD, and his associates at Memorial Sloan Kettering Cancer Center, New York wrote (J Clin Oncol. 2016 Oct 10. doi: 10.1200/JCO.2016.69.0834).
“These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status, and help determine patients’ optimal treatment options.”
The study included 2,186 patients who underwent curative-intent resection of stage 1 non-small cell lung cancer at Memorial Sloan Kettering between 2000 and 2011. The cumulative 5-year lung cancer death rate was 10.4%, but rose with age from 7.5% among patients younger than 65 years to 13.2% among patients who were at least 75 years old. Cumulative 5-year rates of mortality not due to cancer were lower, at 5.3% overall, 1.8% in the youngest cohort, and 9% in the oldest cohort. But a competing risk analysis of the entire cohort showed that non–cancer-specific cumulative mortality was higher than mortality from lung cancer for up to 1.5 years after resection, the investigators found. Furthermore, patients who were at least 75 years old were more likely to die of causes other than cancer for up to 2.5 years after surgery.
In the multivariable analysis, low predicted postoperative diffusing capacity of lung for carbon monoxide (DCLO) independently predicted severe morbidity (P less than .001), 1-year mortality (P less than .001), and non–cancer-specific mortality (P less than .001), the researchers said. These findings reflect prior work linking low DCLO with obstructive, restrictive, and pulmonary vascular disease, chronic heart failure, and poor postoperative outcomes, they noted.
Senior author Prasad S. Adusumilli, MD, provided funding. Dr. Eguchi and Dr. Adusumilli had no relevant financial disclosures.
Patients with stage 1 non–small cell lung cancer who underwent resection with intent to cure were more likely, over the short term, to die of other causes, investigators reported.
“Non–cancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Takashi Eguchi, MD, and his associates at Memorial Sloan Kettering Cancer Center, New York wrote (J Clin Oncol. 2016 Oct 10. doi: 10.1200/JCO.2016.69.0834).
“These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status, and help determine patients’ optimal treatment options.”
The study included 2,186 patients who underwent curative-intent resection of stage 1 non-small cell lung cancer at Memorial Sloan Kettering between 2000 and 2011. The cumulative 5-year lung cancer death rate was 10.4%, but rose with age from 7.5% among patients younger than 65 years to 13.2% among patients who were at least 75 years old. Cumulative 5-year rates of mortality not due to cancer were lower, at 5.3% overall, 1.8% in the youngest cohort, and 9% in the oldest cohort. But a competing risk analysis of the entire cohort showed that non–cancer-specific cumulative mortality was higher than mortality from lung cancer for up to 1.5 years after resection, the investigators found. Furthermore, patients who were at least 75 years old were more likely to die of causes other than cancer for up to 2.5 years after surgery.
In the multivariable analysis, low predicted postoperative diffusing capacity of lung for carbon monoxide (DCLO) independently predicted severe morbidity (P less than .001), 1-year mortality (P less than .001), and non–cancer-specific mortality (P less than .001), the researchers said. These findings reflect prior work linking low DCLO with obstructive, restrictive, and pulmonary vascular disease, chronic heart failure, and poor postoperative outcomes, they noted.
Senior author Prasad S. Adusumilli, MD, provided funding. Dr. Eguchi and Dr. Adusumilli had no relevant financial disclosures.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Patients with resected stage 1 non-small cell lung cancer are more likely to die of other causes in the short term. Major finding: The non–cancer-specific cumulative incidence of death was higher than CID from lung cancer for up to 1.5 years after resection.
Data source: A single-center competing risk analysis of 2,186 patients who underwent curative-intent resection for stage 1 non–small cell lung cancer.
Disclosures: Senior author Prasad Adusumilli, MD, provided funding. Dr. Eguchi and Dr. Adusumilli had no relevant financial disclosures.
Preperitoneal pelvic packing benefits subset of pelvic fracture patients
WAIKOLOA, HAWAII – Preperitoneal pelvic packing reduces mortality in patients with life-threatening hemorrhage caused by unstable pelvic fractures, results from a long-term single-center study showed.
“Despite advances in care of the critically injured patient, mortality rates for patients with hemodynamic instability due to pelvic fractures remains greater than 30%,” Clay Cothren Burlew, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “The majority of trauma centers in the United States use angioembolization for hemorrhage control. While angioembolization is effective in controlling arterial sources of hemorrhage, which constitutes about 15% of pelvic bleeding, it does not address the venous or bony sources of hemorrhage within the pelvis. Additionally, time to arterial hemorrhage control using angioembolization usually takes several hours to accomplish, even at the most advanced level I trauma centers.”
For the current study, the researchers hypothesized that pelvic packing would result in a shorter time to intervention and lower mortality, compared with other pelvic fracture management strategies.
Since September 2004 all patients at the Denver Health Medical Center with persistent hemodynamic instability and a pelvic fracture underwent pelvic packing. Indication for packing is a persistent systolic blood pressure of less than 90 mm Hg in the initial resuscitation period despite the transfusion of two units of red blood cells. “Initial stabilization of the pelvis is performed in the emergency department with a pelvic sheet or a binder,” Dr. Burlew explained. “Skeletal fixation of the pelvis with an external fixator or a pelvic C clamp is done concurrently with preperitoneal pelvic packing in the operating room. Angiography is performed for ongoing pelvic bleeding, defined as greater than four units of red blood cells after the patients’ coagulopathy is corrected; immediate postpacking angiography is performed for ongoing hemodynamic instability despite packing and external fixation.”
Over a period of 11 years, 2,293 patients were admitted to Denver Health Medical Center with pelvic fractures. Of these, 128 patients in refractory shock underwent pelvic packing. More than half of the patients (70%) were men, their mean age was 44 years, and their mean Injury Severity Score was 48. The most common mechanism of injury was motor vehicle collision, followed by auto/pedestrian accidents and motorcycle collision. Pelvic fracture patterns included every classification, with anterior posterior compression (APC) III and lateral compression (LC) II patterns predominating. Of these, 18 patients had open pelvic fractures. More than half of patients (70%) had an extremity injury, 65% had a thoracic injury, 63% had an abdominal injury, 43% had a traumatic brain injury, and 38% had a spine injury.
The mean systolic blood pressure of patients was 74 mm Hg and their mean heart rate was 120 beats per minute in the emergency department. Their mean base deficit was 12. However, 32% of patients did not have an arterial blood gas reported during this time frame. When the researchers compared 13% of patients who underwent postpacking angioembolization with those who did not require angioembolization after pelvic packing, they observed no significant differences in age, injury severity score, presenting systolic BP, presenting systolic BP/base deficit, or ED transfusions. The only difference that reached statistical significance was a lower heart rate in the ED in the postpacking angioembolization group, compared with the preperitoneal pelvic packing alone group (110 vs. 121 beats per minute). “We also realized that the angioembolization group received more red blood cells and fresh frozen plasma prior to ICU admission, as well as in the subsequent 24 hours,” Dr. Burlew said.
The majority of patients (84%) had a single packing of the preperitoneal space, while 20 patients underwent repacking when returned to the operating room; all occurred prior to July 2011. “At this time point we determined that there was an increased infection rate with repacking of the pelvis,” Dr. Burlew said. “There were 15 pelvic space infections. Four occurred in those with open fractures or perineal degloving, four developed in those with associated bladder injuries, and seven pelvic space infections occurred in patients without an open fracture.” The infection rate was 6% among patients with a single packing of the pelvis, compared with an infection rate of 45% among those who underwent repacking. “This emphasizes the need for local control of small bleeders when the pelvis in unpacked, using electrocautery and topical hemostatic agents,” she said.
Dr. Burlew went on to note that comparison of two prospective observational study groups with differing management schema may provide salient information. “The AAST multicenter study was an evaluation of the modern-day care of pelvic fracture patients from 11 different centers,” she said. “In that study, the mortality rate among patients presenting in shock who did not undergo pelvic packing was 32%. The mortality rate in our series was 21%, with a relative risk reduction that was statistically significant.” She concluded that pelvic packing “has a faster time to intervention for pelvic fracture–related hemorrhage. Arterial bleed was only present in 13% of patients, rendering angiography of limited utility. Pelvic packing should be utilized for pelvic fracture–related bleeding in the patient who remains hemodynamically unstable despite red blood cell transfusion.”
One of the study authors, Ernest E. Moore, MD, disclosed that he has received research funding from Haemonetics, TEM, and Prytime Medical Devices, and Charles J. Fox, MD, is on the clinical advisory board for Prytime Medical Devices. Dr. Burlew reported having no financial disclosures.
WAIKOLOA, HAWAII – Preperitoneal pelvic packing reduces mortality in patients with life-threatening hemorrhage caused by unstable pelvic fractures, results from a long-term single-center study showed.
“Despite advances in care of the critically injured patient, mortality rates for patients with hemodynamic instability due to pelvic fractures remains greater than 30%,” Clay Cothren Burlew, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “The majority of trauma centers in the United States use angioembolization for hemorrhage control. While angioembolization is effective in controlling arterial sources of hemorrhage, which constitutes about 15% of pelvic bleeding, it does not address the venous or bony sources of hemorrhage within the pelvis. Additionally, time to arterial hemorrhage control using angioembolization usually takes several hours to accomplish, even at the most advanced level I trauma centers.”
For the current study, the researchers hypothesized that pelvic packing would result in a shorter time to intervention and lower mortality, compared with other pelvic fracture management strategies.
Since September 2004 all patients at the Denver Health Medical Center with persistent hemodynamic instability and a pelvic fracture underwent pelvic packing. Indication for packing is a persistent systolic blood pressure of less than 90 mm Hg in the initial resuscitation period despite the transfusion of two units of red blood cells. “Initial stabilization of the pelvis is performed in the emergency department with a pelvic sheet or a binder,” Dr. Burlew explained. “Skeletal fixation of the pelvis with an external fixator or a pelvic C clamp is done concurrently with preperitoneal pelvic packing in the operating room. Angiography is performed for ongoing pelvic bleeding, defined as greater than four units of red blood cells after the patients’ coagulopathy is corrected; immediate postpacking angiography is performed for ongoing hemodynamic instability despite packing and external fixation.”
Over a period of 11 years, 2,293 patients were admitted to Denver Health Medical Center with pelvic fractures. Of these, 128 patients in refractory shock underwent pelvic packing. More than half of the patients (70%) were men, their mean age was 44 years, and their mean Injury Severity Score was 48. The most common mechanism of injury was motor vehicle collision, followed by auto/pedestrian accidents and motorcycle collision. Pelvic fracture patterns included every classification, with anterior posterior compression (APC) III and lateral compression (LC) II patterns predominating. Of these, 18 patients had open pelvic fractures. More than half of patients (70%) had an extremity injury, 65% had a thoracic injury, 63% had an abdominal injury, 43% had a traumatic brain injury, and 38% had a spine injury.
The mean systolic blood pressure of patients was 74 mm Hg and their mean heart rate was 120 beats per minute in the emergency department. Their mean base deficit was 12. However, 32% of patients did not have an arterial blood gas reported during this time frame. When the researchers compared 13% of patients who underwent postpacking angioembolization with those who did not require angioembolization after pelvic packing, they observed no significant differences in age, injury severity score, presenting systolic BP, presenting systolic BP/base deficit, or ED transfusions. The only difference that reached statistical significance was a lower heart rate in the ED in the postpacking angioembolization group, compared with the preperitoneal pelvic packing alone group (110 vs. 121 beats per minute). “We also realized that the angioembolization group received more red blood cells and fresh frozen plasma prior to ICU admission, as well as in the subsequent 24 hours,” Dr. Burlew said.
The majority of patients (84%) had a single packing of the preperitoneal space, while 20 patients underwent repacking when returned to the operating room; all occurred prior to July 2011. “At this time point we determined that there was an increased infection rate with repacking of the pelvis,” Dr. Burlew said. “There were 15 pelvic space infections. Four occurred in those with open fractures or perineal degloving, four developed in those with associated bladder injuries, and seven pelvic space infections occurred in patients without an open fracture.” The infection rate was 6% among patients with a single packing of the pelvis, compared with an infection rate of 45% among those who underwent repacking. “This emphasizes the need for local control of small bleeders when the pelvis in unpacked, using electrocautery and topical hemostatic agents,” she said.
Dr. Burlew went on to note that comparison of two prospective observational study groups with differing management schema may provide salient information. “The AAST multicenter study was an evaluation of the modern-day care of pelvic fracture patients from 11 different centers,” she said. “In that study, the mortality rate among patients presenting in shock who did not undergo pelvic packing was 32%. The mortality rate in our series was 21%, with a relative risk reduction that was statistically significant.” She concluded that pelvic packing “has a faster time to intervention for pelvic fracture–related hemorrhage. Arterial bleed was only present in 13% of patients, rendering angiography of limited utility. Pelvic packing should be utilized for pelvic fracture–related bleeding in the patient who remains hemodynamically unstable despite red blood cell transfusion.”
One of the study authors, Ernest E. Moore, MD, disclosed that he has received research funding from Haemonetics, TEM, and Prytime Medical Devices, and Charles J. Fox, MD, is on the clinical advisory board for Prytime Medical Devices. Dr. Burlew reported having no financial disclosures.
WAIKOLOA, HAWAII – Preperitoneal pelvic packing reduces mortality in patients with life-threatening hemorrhage caused by unstable pelvic fractures, results from a long-term single-center study showed.
“Despite advances in care of the critically injured patient, mortality rates for patients with hemodynamic instability due to pelvic fractures remains greater than 30%,” Clay Cothren Burlew, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “The majority of trauma centers in the United States use angioembolization for hemorrhage control. While angioembolization is effective in controlling arterial sources of hemorrhage, which constitutes about 15% of pelvic bleeding, it does not address the venous or bony sources of hemorrhage within the pelvis. Additionally, time to arterial hemorrhage control using angioembolization usually takes several hours to accomplish, even at the most advanced level I trauma centers.”
For the current study, the researchers hypothesized that pelvic packing would result in a shorter time to intervention and lower mortality, compared with other pelvic fracture management strategies.
Since September 2004 all patients at the Denver Health Medical Center with persistent hemodynamic instability and a pelvic fracture underwent pelvic packing. Indication for packing is a persistent systolic blood pressure of less than 90 mm Hg in the initial resuscitation period despite the transfusion of two units of red blood cells. “Initial stabilization of the pelvis is performed in the emergency department with a pelvic sheet or a binder,” Dr. Burlew explained. “Skeletal fixation of the pelvis with an external fixator or a pelvic C clamp is done concurrently with preperitoneal pelvic packing in the operating room. Angiography is performed for ongoing pelvic bleeding, defined as greater than four units of red blood cells after the patients’ coagulopathy is corrected; immediate postpacking angiography is performed for ongoing hemodynamic instability despite packing and external fixation.”
Over a period of 11 years, 2,293 patients were admitted to Denver Health Medical Center with pelvic fractures. Of these, 128 patients in refractory shock underwent pelvic packing. More than half of the patients (70%) were men, their mean age was 44 years, and their mean Injury Severity Score was 48. The most common mechanism of injury was motor vehicle collision, followed by auto/pedestrian accidents and motorcycle collision. Pelvic fracture patterns included every classification, with anterior posterior compression (APC) III and lateral compression (LC) II patterns predominating. Of these, 18 patients had open pelvic fractures. More than half of patients (70%) had an extremity injury, 65% had a thoracic injury, 63% had an abdominal injury, 43% had a traumatic brain injury, and 38% had a spine injury.
The mean systolic blood pressure of patients was 74 mm Hg and their mean heart rate was 120 beats per minute in the emergency department. Their mean base deficit was 12. However, 32% of patients did not have an arterial blood gas reported during this time frame. When the researchers compared 13% of patients who underwent postpacking angioembolization with those who did not require angioembolization after pelvic packing, they observed no significant differences in age, injury severity score, presenting systolic BP, presenting systolic BP/base deficit, or ED transfusions. The only difference that reached statistical significance was a lower heart rate in the ED in the postpacking angioembolization group, compared with the preperitoneal pelvic packing alone group (110 vs. 121 beats per minute). “We also realized that the angioembolization group received more red blood cells and fresh frozen plasma prior to ICU admission, as well as in the subsequent 24 hours,” Dr. Burlew said.
The majority of patients (84%) had a single packing of the preperitoneal space, while 20 patients underwent repacking when returned to the operating room; all occurred prior to July 2011. “At this time point we determined that there was an increased infection rate with repacking of the pelvis,” Dr. Burlew said. “There were 15 pelvic space infections. Four occurred in those with open fractures or perineal degloving, four developed in those with associated bladder injuries, and seven pelvic space infections occurred in patients without an open fracture.” The infection rate was 6% among patients with a single packing of the pelvis, compared with an infection rate of 45% among those who underwent repacking. “This emphasizes the need for local control of small bleeders when the pelvis in unpacked, using electrocautery and topical hemostatic agents,” she said.
Dr. Burlew went on to note that comparison of two prospective observational study groups with differing management schema may provide salient information. “The AAST multicenter study was an evaluation of the modern-day care of pelvic fracture patients from 11 different centers,” she said. “In that study, the mortality rate among patients presenting in shock who did not undergo pelvic packing was 32%. The mortality rate in our series was 21%, with a relative risk reduction that was statistically significant.” She concluded that pelvic packing “has a faster time to intervention for pelvic fracture–related hemorrhage. Arterial bleed was only present in 13% of patients, rendering angiography of limited utility. Pelvic packing should be utilized for pelvic fracture–related bleeding in the patient who remains hemodynamically unstable despite red blood cell transfusion.”
One of the study authors, Ernest E. Moore, MD, disclosed that he has received research funding from Haemonetics, TEM, and Prytime Medical Devices, and Charles J. Fox, MD, is on the clinical advisory board for Prytime Medical Devices. Dr. Burlew reported having no financial disclosures.
Key clinical point:
Major finding: Of the 128 patients who underwent preperitoneal pelvic packing for life-threatening hemorrhage caused by unstable pelvic fractures, 27 died, for a mortality rate of 21%, which is significantly lower than other analyses in the medical literature.
Data source: An 11-year study of 2,293 patients who were admitted to Denver Health Medical Center with pelvic fractures.
Disclosures: One of the study authors, Ernest E. Moore, MD, disclosed that he has received research funding from Haemonetics, TEM, and Prytime Medical Devices, and Charles J. Fox, MD, is on the clinical advisory board for Prytime Medical Devices. Dr. Burlew reported having no financial disclosures.