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Spray-painted bandages and pharma sings ‘Dough Canada!’
He’s not quite dead yet!
In 2015, Benjamin Schreiber, an Iowa man convicted of murder and sentenced to life in prison without parole, developed a case of septic poisoning because of large, untreated kidney stones. While at the hospital, his heart stopped several times, requiring resuscitation. After being stabilized, he underwent surgery to remove the kidney stones and was then released back to his prison cell.
Fast forward to 2018. Mr. Schreiber filed for relief from his conviction, arguing that, because he technically died, his life sentence had been served and he should be released. While the logic is impeccable, an Iowa district court didn’t buy it, noting that the fact that Mr. Schreiber was able to submit a petition for his release “confirms the petitioner’s current status as living.”
Sadly for Mr. Schreiber, the Iowa Court of Appeals agreed with the lower court’s decision. In a wonderfully pithy summation of the case, Judge Amanda Potterfield wrote: “Schreiber is either still alive, in which case he must remain in prison, or he is actually dead, in which case this appeal is moot.”
While the Livin’ on the MDedge team is glad that a convicted murderer will not be released back into the public, we salute his devotion to the art of technicality. The judges may not have been convinced, but you’re dead to us, Mr. Schreiber.
Breaking news: Drug companies gouge consumers
Canada. It’s home to many things: Trees, glaciers, beavers, and several people. But we Americans also know it as the home of cheap drugs. It may be borderline illegal, but that’s never stopped America from taking things that don’t belong to us before.
You’d think then that it’d be great being sick in Canada. But it turns out that many of those poor, desperate souls living in the frozen tundra of the north are actually overpaying for drugs just like the rest of us, according to research published in the Canadian Medical Association Journal.
It all comes down to those strange items called drug discount cards. They’re coupons offered by brand-name drug manufacturers to keep patients from switching to cheap generics.
Sounds great, right? Well, while a few patients saw savings, the average cost to patients with public insurance increased by 1.3% over generics. And if you were unfortunate enough to have private insurance, you’d be paying 46% more using the cards rather than generics. In some instances, patients were paying a whole $10 more for a prescription of the name brand, compared with the generic. And we thought Tim Hortons was our northern neighbor’s only company making a lot of dough. Ten loonies more per Rx ain’t Timbits.
So, Canada, how does it feel to have your health care made fun of? U-S-A! U-S-A! Now, if you’ll excuse us, we’re off to pay $1,000 a pill to cure us some hepatitis C. That’s some real red-blooded American price gouging right there.
This looks like a job for vacuum science
The LOTME staff, of course, scans a veritable buffet of sources to come up with the tasty tidbits we present each week to our deliciously wonderful and highly scrumptious readers each week.
One of our favorite sauces … umm, we mean sources, and the home of a tantalizing medical morsel (can you tell it’s almost lunch time?), is the Journal of Vacuum Science and Technology B. That’s B, not A. Anyone, at least anyone who’s serious about vacuum science, will tell you that the Journal of Vacuum Science and Technology A is pretty much a bottomless pit of trolling, political bickering, and popular nonsense. But B, now that’s a different story.
B is where we meet the EStAD (electrostatic and air driven) device. EStAD is a portable device that may someday offer physicians and first responders a way to treat wounds in rural areas where immediate care may not be available, the investigators said.
EStAD, using a process called electrospinning along with a confined electric field, works like a can of spray paint to deposit a fiber mat, which could be a bandage or a drug, onto a wound.
The device is still under development, but the research team reports that it has been successfully tested on a porcine skin incision and a gloved human hand.
The next step in EStAD development is to bring it to Washington, where the investigators will see if spray-on bandages can stand up to the hot air coming out of politicians’ mouths. We’re hoping that they sell tickets.
He’s not quite dead yet!
In 2015, Benjamin Schreiber, an Iowa man convicted of murder and sentenced to life in prison without parole, developed a case of septic poisoning because of large, untreated kidney stones. While at the hospital, his heart stopped several times, requiring resuscitation. After being stabilized, he underwent surgery to remove the kidney stones and was then released back to his prison cell.
Fast forward to 2018. Mr. Schreiber filed for relief from his conviction, arguing that, because he technically died, his life sentence had been served and he should be released. While the logic is impeccable, an Iowa district court didn’t buy it, noting that the fact that Mr. Schreiber was able to submit a petition for his release “confirms the petitioner’s current status as living.”
Sadly for Mr. Schreiber, the Iowa Court of Appeals agreed with the lower court’s decision. In a wonderfully pithy summation of the case, Judge Amanda Potterfield wrote: “Schreiber is either still alive, in which case he must remain in prison, or he is actually dead, in which case this appeal is moot.”
While the Livin’ on the MDedge team is glad that a convicted murderer will not be released back into the public, we salute his devotion to the art of technicality. The judges may not have been convinced, but you’re dead to us, Mr. Schreiber.
Breaking news: Drug companies gouge consumers
Canada. It’s home to many things: Trees, glaciers, beavers, and several people. But we Americans also know it as the home of cheap drugs. It may be borderline illegal, but that’s never stopped America from taking things that don’t belong to us before.
You’d think then that it’d be great being sick in Canada. But it turns out that many of those poor, desperate souls living in the frozen tundra of the north are actually overpaying for drugs just like the rest of us, according to research published in the Canadian Medical Association Journal.
It all comes down to those strange items called drug discount cards. They’re coupons offered by brand-name drug manufacturers to keep patients from switching to cheap generics.
Sounds great, right? Well, while a few patients saw savings, the average cost to patients with public insurance increased by 1.3% over generics. And if you were unfortunate enough to have private insurance, you’d be paying 46% more using the cards rather than generics. In some instances, patients were paying a whole $10 more for a prescription of the name brand, compared with the generic. And we thought Tim Hortons was our northern neighbor’s only company making a lot of dough. Ten loonies more per Rx ain’t Timbits.
So, Canada, how does it feel to have your health care made fun of? U-S-A! U-S-A! Now, if you’ll excuse us, we’re off to pay $1,000 a pill to cure us some hepatitis C. That’s some real red-blooded American price gouging right there.
This looks like a job for vacuum science
The LOTME staff, of course, scans a veritable buffet of sources to come up with the tasty tidbits we present each week to our deliciously wonderful and highly scrumptious readers each week.
One of our favorite sauces … umm, we mean sources, and the home of a tantalizing medical morsel (can you tell it’s almost lunch time?), is the Journal of Vacuum Science and Technology B. That’s B, not A. Anyone, at least anyone who’s serious about vacuum science, will tell you that the Journal of Vacuum Science and Technology A is pretty much a bottomless pit of trolling, political bickering, and popular nonsense. But B, now that’s a different story.
B is where we meet the EStAD (electrostatic and air driven) device. EStAD is a portable device that may someday offer physicians and first responders a way to treat wounds in rural areas where immediate care may not be available, the investigators said.
EStAD, using a process called electrospinning along with a confined electric field, works like a can of spray paint to deposit a fiber mat, which could be a bandage or a drug, onto a wound.
The device is still under development, but the research team reports that it has been successfully tested on a porcine skin incision and a gloved human hand.
The next step in EStAD development is to bring it to Washington, where the investigators will see if spray-on bandages can stand up to the hot air coming out of politicians’ mouths. We’re hoping that they sell tickets.
He’s not quite dead yet!
In 2015, Benjamin Schreiber, an Iowa man convicted of murder and sentenced to life in prison without parole, developed a case of septic poisoning because of large, untreated kidney stones. While at the hospital, his heart stopped several times, requiring resuscitation. After being stabilized, he underwent surgery to remove the kidney stones and was then released back to his prison cell.
Fast forward to 2018. Mr. Schreiber filed for relief from his conviction, arguing that, because he technically died, his life sentence had been served and he should be released. While the logic is impeccable, an Iowa district court didn’t buy it, noting that the fact that Mr. Schreiber was able to submit a petition for his release “confirms the petitioner’s current status as living.”
Sadly for Mr. Schreiber, the Iowa Court of Appeals agreed with the lower court’s decision. In a wonderfully pithy summation of the case, Judge Amanda Potterfield wrote: “Schreiber is either still alive, in which case he must remain in prison, or he is actually dead, in which case this appeal is moot.”
While the Livin’ on the MDedge team is glad that a convicted murderer will not be released back into the public, we salute his devotion to the art of technicality. The judges may not have been convinced, but you’re dead to us, Mr. Schreiber.
Breaking news: Drug companies gouge consumers
Canada. It’s home to many things: Trees, glaciers, beavers, and several people. But we Americans also know it as the home of cheap drugs. It may be borderline illegal, but that’s never stopped America from taking things that don’t belong to us before.
You’d think then that it’d be great being sick in Canada. But it turns out that many of those poor, desperate souls living in the frozen tundra of the north are actually overpaying for drugs just like the rest of us, according to research published in the Canadian Medical Association Journal.
It all comes down to those strange items called drug discount cards. They’re coupons offered by brand-name drug manufacturers to keep patients from switching to cheap generics.
Sounds great, right? Well, while a few patients saw savings, the average cost to patients with public insurance increased by 1.3% over generics. And if you were unfortunate enough to have private insurance, you’d be paying 46% more using the cards rather than generics. In some instances, patients were paying a whole $10 more for a prescription of the name brand, compared with the generic. And we thought Tim Hortons was our northern neighbor’s only company making a lot of dough. Ten loonies more per Rx ain’t Timbits.
So, Canada, how does it feel to have your health care made fun of? U-S-A! U-S-A! Now, if you’ll excuse us, we’re off to pay $1,000 a pill to cure us some hepatitis C. That’s some real red-blooded American price gouging right there.
This looks like a job for vacuum science
The LOTME staff, of course, scans a veritable buffet of sources to come up with the tasty tidbits we present each week to our deliciously wonderful and highly scrumptious readers each week.
One of our favorite sauces … umm, we mean sources, and the home of a tantalizing medical morsel (can you tell it’s almost lunch time?), is the Journal of Vacuum Science and Technology B. That’s B, not A. Anyone, at least anyone who’s serious about vacuum science, will tell you that the Journal of Vacuum Science and Technology A is pretty much a bottomless pit of trolling, political bickering, and popular nonsense. But B, now that’s a different story.
B is where we meet the EStAD (electrostatic and air driven) device. EStAD is a portable device that may someday offer physicians and first responders a way to treat wounds in rural areas where immediate care may not be available, the investigators said.
EStAD, using a process called electrospinning along with a confined electric field, works like a can of spray paint to deposit a fiber mat, which could be a bandage or a drug, onto a wound.
The device is still under development, but the research team reports that it has been successfully tested on a porcine skin incision and a gloved human hand.
The next step in EStAD development is to bring it to Washington, where the investigators will see if spray-on bandages can stand up to the hot air coming out of politicians’ mouths. We’re hoping that they sell tickets.
Oral anticancer spending in Part D tied in major part to price increases
Price increases are the main source of the increase in spending on oral anticancer drugs in the Medicare Part D prescription drug program, according to new research.
“Annualized spending on the same oral anticancer drugs more than doubled in a 5-year period,” Kira Seiger from Harvard Medical School, Boston, and colleagues wrote in a research letter published online in JAMA Oncology.
“Use increased substantially, likely owing to expanded drug indications, increased Medicare Part D enrollment, and declining cancer mortality yielding longer treatment courses,” the authors continued. “However, increased spending was predominantly driven (56%) by rising drug costs, which is reflective of pharmaceutical pricing strategies.”
Increased use of these drugs accounted for 44% of the annualized spending on the 56 oral anticancer drugs in this study.
Researchers found that from 2007 through 2013, “anticancer drugs prices increased 5% above inflation annually, plus 10% per subsequent indication approved. Results of this study demonstrated a continued rise from 2013 through 2017 with a compound annual growth rate of 13% above inflation for drug cost per beneficiary.”
Ms. Seiger and colleagues noted that, from 2013 through 2017, more than $41.4 billion was spent on the 56 oral anticancer drugs examined for the study. These drugs carried an average out-of-pocket cost of $551, accounting for $2.1 billion of the amount spent on these drugs.
“High drug prices on market entry are often attributed to research and development expenses, though research and development may not explain the subsequent increases in drug costs demonstrated in this study,” the researchers stated.
They recommended policy makers consider capping price increases at a set percentage above inflation, “especially given that rising use reflects increased need for these therapies.”
The study was sponsored in part by the department of dermatology at Brigham and Women’s Hospital, Boston. Three of the five authors reported received fees from pharmaceutical manufacturers, and one reported serving as chair for the National Comprehensive Cancer Network.
SOURCE: Kira Seiger et al. JAMA Oncology. doi: 10.1001/jamaoncol.2019.4906.
Price increases are the main source of the increase in spending on oral anticancer drugs in the Medicare Part D prescription drug program, according to new research.
“Annualized spending on the same oral anticancer drugs more than doubled in a 5-year period,” Kira Seiger from Harvard Medical School, Boston, and colleagues wrote in a research letter published online in JAMA Oncology.
“Use increased substantially, likely owing to expanded drug indications, increased Medicare Part D enrollment, and declining cancer mortality yielding longer treatment courses,” the authors continued. “However, increased spending was predominantly driven (56%) by rising drug costs, which is reflective of pharmaceutical pricing strategies.”
Increased use of these drugs accounted for 44% of the annualized spending on the 56 oral anticancer drugs in this study.
Researchers found that from 2007 through 2013, “anticancer drugs prices increased 5% above inflation annually, plus 10% per subsequent indication approved. Results of this study demonstrated a continued rise from 2013 through 2017 with a compound annual growth rate of 13% above inflation for drug cost per beneficiary.”
Ms. Seiger and colleagues noted that, from 2013 through 2017, more than $41.4 billion was spent on the 56 oral anticancer drugs examined for the study. These drugs carried an average out-of-pocket cost of $551, accounting for $2.1 billion of the amount spent on these drugs.
“High drug prices on market entry are often attributed to research and development expenses, though research and development may not explain the subsequent increases in drug costs demonstrated in this study,” the researchers stated.
They recommended policy makers consider capping price increases at a set percentage above inflation, “especially given that rising use reflects increased need for these therapies.”
The study was sponsored in part by the department of dermatology at Brigham and Women’s Hospital, Boston. Three of the five authors reported received fees from pharmaceutical manufacturers, and one reported serving as chair for the National Comprehensive Cancer Network.
SOURCE: Kira Seiger et al. JAMA Oncology. doi: 10.1001/jamaoncol.2019.4906.
Price increases are the main source of the increase in spending on oral anticancer drugs in the Medicare Part D prescription drug program, according to new research.
“Annualized spending on the same oral anticancer drugs more than doubled in a 5-year period,” Kira Seiger from Harvard Medical School, Boston, and colleagues wrote in a research letter published online in JAMA Oncology.
“Use increased substantially, likely owing to expanded drug indications, increased Medicare Part D enrollment, and declining cancer mortality yielding longer treatment courses,” the authors continued. “However, increased spending was predominantly driven (56%) by rising drug costs, which is reflective of pharmaceutical pricing strategies.”
Increased use of these drugs accounted for 44% of the annualized spending on the 56 oral anticancer drugs in this study.
Researchers found that from 2007 through 2013, “anticancer drugs prices increased 5% above inflation annually, plus 10% per subsequent indication approved. Results of this study demonstrated a continued rise from 2013 through 2017 with a compound annual growth rate of 13% above inflation for drug cost per beneficiary.”
Ms. Seiger and colleagues noted that, from 2013 through 2017, more than $41.4 billion was spent on the 56 oral anticancer drugs examined for the study. These drugs carried an average out-of-pocket cost of $551, accounting for $2.1 billion of the amount spent on these drugs.
“High drug prices on market entry are often attributed to research and development expenses, though research and development may not explain the subsequent increases in drug costs demonstrated in this study,” the researchers stated.
They recommended policy makers consider capping price increases at a set percentage above inflation, “especially given that rising use reflects increased need for these therapies.”
The study was sponsored in part by the department of dermatology at Brigham and Women’s Hospital, Boston. Three of the five authors reported received fees from pharmaceutical manufacturers, and one reported serving as chair for the National Comprehensive Cancer Network.
SOURCE: Kira Seiger et al. JAMA Oncology. doi: 10.1001/jamaoncol.2019.4906.
FROM JAMA ONCOLOGY
Sentinel node biopsy safe for women with vulval cancer
Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.
One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.
Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.
In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.
Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.
The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.
Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.
Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.
The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.
“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”
No conflicts of interest were declared.
SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.
Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.
One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.
Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.
In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.
Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.
The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.
Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.
Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.
The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.
“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”
No conflicts of interest were declared.
SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.
Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.
One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.
Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.
In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.
Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.
The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.
Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.
Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.
The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.
“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”
No conflicts of interest were declared.
SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.
FROM GYNECOLOGIC ONCOLOGY
‘Tis the season to reflect and take stock
‘Tis the season to reflect and take stock: Maybe you had a baby, or learned a new procedure, or bought a Tesla? Of course, you made (loads of?) money and treated many patients. Imagine if I asked you this in person, what would you reply? And what made you most proud? I’d tell you this story.
Last week I saw a 50-something-year-old woman for her annual skin screening. She asked if I remembered her mother, who was also my patient. Squinting through my dermatoscope at the nevi on her back, I tried to recall. “Yes, I think so.” (Actually, I was unsure.)
“Well she passed away last week from breast cancer,” she said.
“Oh, I’m sorry to hear that,” I replied.
She added: “Yes, yet she lived much longer than we thought. I want you to know we believe it was in large part because of you.”
I stopped and wheeled around to face her. How could that possibly be true? I had only treated her for a simple skin cancer. She explained that I had seen her mom about a year ago and cut out a skin cancer on her face. Her mom was afraid of needles and of surgery. Apparently when she asked me if it would hurt, I replied: “Well, most patients, yes, but not you.” Pausing, I added: “Because you’re a tough old bird.” She laughed. Apparently that warmth I conveyed and display of confidence in her was just what she needed at that moment. She didn’t flinch.
Not long after, she was diagnosed with breast cancer. When given the news with her children present, she replied, “well, I’ll just fight it. I’m a tough old bird.” It was just what they needed in that moment. “I’m a tough old bird” became their rally cry. Apparently with each stage, surgery, radiation, chemo, they fell back on it. Her son had “Tough Old Bird” made into a magnet and prominently posted on the refrigerator door where she would see it every day.
Sadly, she ultimately succumbed to her disease, but did so later than had been expected and having fought all the way. My patient teared up and asked if she could give me a hug on behalf of her mom. “Thank you, Dr. Benabio. We won’t forget what you did for her.”
I did recall her now, remembering even what exam room she was in when I said it. Yet, I had no idea what I had done. I wonder how many others there were. Of the many things you accomplished this year, try to recall these achievements. Not the psoriasis cleared, or tumor extirpated, or new homes bought. But the comfort and care you brought to the mother with worry, the father with anguish, the daughter with anxieties, or the son with misdeeds.
It is a beautiful, hard, and joyous life we have as physicians, for our “happiness lies in the absorption in some vocation which satisfies the soul; that we are here to add what we can to, not get what we can from life.”* How fortunate are we. Take stock.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
Reference
*William Osler, “Doctor and Nurse.” Address given at Training School for Nurses at Johns Hopkins Hospital, June 4, 1891
‘Tis the season to reflect and take stock: Maybe you had a baby, or learned a new procedure, or bought a Tesla? Of course, you made (loads of?) money and treated many patients. Imagine if I asked you this in person, what would you reply? And what made you most proud? I’d tell you this story.
Last week I saw a 50-something-year-old woman for her annual skin screening. She asked if I remembered her mother, who was also my patient. Squinting through my dermatoscope at the nevi on her back, I tried to recall. “Yes, I think so.” (Actually, I was unsure.)
“Well she passed away last week from breast cancer,” she said.
“Oh, I’m sorry to hear that,” I replied.
She added: “Yes, yet she lived much longer than we thought. I want you to know we believe it was in large part because of you.”
I stopped and wheeled around to face her. How could that possibly be true? I had only treated her for a simple skin cancer. She explained that I had seen her mom about a year ago and cut out a skin cancer on her face. Her mom was afraid of needles and of surgery. Apparently when she asked me if it would hurt, I replied: “Well, most patients, yes, but not you.” Pausing, I added: “Because you’re a tough old bird.” She laughed. Apparently that warmth I conveyed and display of confidence in her was just what she needed at that moment. She didn’t flinch.
Not long after, she was diagnosed with breast cancer. When given the news with her children present, she replied, “well, I’ll just fight it. I’m a tough old bird.” It was just what they needed in that moment. “I’m a tough old bird” became their rally cry. Apparently with each stage, surgery, radiation, chemo, they fell back on it. Her son had “Tough Old Bird” made into a magnet and prominently posted on the refrigerator door where she would see it every day.
Sadly, she ultimately succumbed to her disease, but did so later than had been expected and having fought all the way. My patient teared up and asked if she could give me a hug on behalf of her mom. “Thank you, Dr. Benabio. We won’t forget what you did for her.”
I did recall her now, remembering even what exam room she was in when I said it. Yet, I had no idea what I had done. I wonder how many others there were. Of the many things you accomplished this year, try to recall these achievements. Not the psoriasis cleared, or tumor extirpated, or new homes bought. But the comfort and care you brought to the mother with worry, the father with anguish, the daughter with anxieties, or the son with misdeeds.
It is a beautiful, hard, and joyous life we have as physicians, for our “happiness lies in the absorption in some vocation which satisfies the soul; that we are here to add what we can to, not get what we can from life.”* How fortunate are we. Take stock.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
Reference
*William Osler, “Doctor and Nurse.” Address given at Training School for Nurses at Johns Hopkins Hospital, June 4, 1891
‘Tis the season to reflect and take stock: Maybe you had a baby, or learned a new procedure, or bought a Tesla? Of course, you made (loads of?) money and treated many patients. Imagine if I asked you this in person, what would you reply? And what made you most proud? I’d tell you this story.
Last week I saw a 50-something-year-old woman for her annual skin screening. She asked if I remembered her mother, who was also my patient. Squinting through my dermatoscope at the nevi on her back, I tried to recall. “Yes, I think so.” (Actually, I was unsure.)
“Well she passed away last week from breast cancer,” she said.
“Oh, I’m sorry to hear that,” I replied.
She added: “Yes, yet she lived much longer than we thought. I want you to know we believe it was in large part because of you.”
I stopped and wheeled around to face her. How could that possibly be true? I had only treated her for a simple skin cancer. She explained that I had seen her mom about a year ago and cut out a skin cancer on her face. Her mom was afraid of needles and of surgery. Apparently when she asked me if it would hurt, I replied: “Well, most patients, yes, but not you.” Pausing, I added: “Because you’re a tough old bird.” She laughed. Apparently that warmth I conveyed and display of confidence in her was just what she needed at that moment. She didn’t flinch.
Not long after, she was diagnosed with breast cancer. When given the news with her children present, she replied, “well, I’ll just fight it. I’m a tough old bird.” It was just what they needed in that moment. “I’m a tough old bird” became their rally cry. Apparently with each stage, surgery, radiation, chemo, they fell back on it. Her son had “Tough Old Bird” made into a magnet and prominently posted on the refrigerator door where she would see it every day.
Sadly, she ultimately succumbed to her disease, but did so later than had been expected and having fought all the way. My patient teared up and asked if she could give me a hug on behalf of her mom. “Thank you, Dr. Benabio. We won’t forget what you did for her.”
I did recall her now, remembering even what exam room she was in when I said it. Yet, I had no idea what I had done. I wonder how many others there were. Of the many things you accomplished this year, try to recall these achievements. Not the psoriasis cleared, or tumor extirpated, or new homes bought. But the comfort and care you brought to the mother with worry, the father with anguish, the daughter with anxieties, or the son with misdeeds.
It is a beautiful, hard, and joyous life we have as physicians, for our “happiness lies in the absorption in some vocation which satisfies the soul; that we are here to add what we can to, not get what we can from life.”* How fortunate are we. Take stock.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
Reference
*William Osler, “Doctor and Nurse.” Address given at Training School for Nurses at Johns Hopkins Hospital, June 4, 1891
Foundation launches direct-to-patient registry in multiple myeloma
The Multiple Myeloma Research Foundation (MMRF) recently launched its Direct-to-Patient registry, in what the organization’s leaders are describing as a “disruptive” step toward improving outcomes for patients with multiple myeloma.
The new registry is intended to build upon CoMMpass, a program started 8 years ago that now represents the largest genomic database of any type of cancer. Although CoMMpass includes data from about 1,150 patients with myeloma, it’s not enough information, according to the chief marketing and development officer at the MMRF, Anne Quinn Young.
“For a disease as heterogenous as myeloma is, we need more, particularly because we don’t have all the samples for later-stage disease,” Ms. Quinn Young said in an interview. “And even with the clinical data, given the patient population, both [in terms of] demographics and the nature of the disease, the numbers of patients still living after multiple relapses is rather small.”
In an earlier effort to gather more data, the MMRF first turned to other organizations for help, but this approach fell short because of scarcity of data, and in some cases, unwillingness to share. Steven Labkoff, MD, chief data officer at the MMRF, described this experience in an interview.
“When the MMRF was looking around for different data sources for myeloma data, it was always the claim that, ‘Sure, we have plenty of patients, we have plenty of data, and it’s rich and really complete.’ However, as we approached an array of organizations – big organizations – as we dug into the details and reviewed patient counts or data completeness, they either didn’t have a sufficient number of patients, they didn’t have sufficiently complete data for our needs, and in the case where some did have sufficient numbers and complete data sets, they simply weren’t in a position to share that data outside their institution,” Dr. Labkoff said.
Undeterred, the MMRF switched tactics to the current, patient-centric approach.
“We’re leveraging one aspect of the HIPAA legislation,” Dr. Labkoff said, referring to patients’ rights to request their own medical records and an institution’s legal obligation to provide those records.
In the short-term, the registry will collect three types of data: patient donated data (answers from a patient survey), electronic medical records abstracted from all relevant past providers, and genomic test results. Participating patients will have blood drawn at home by a phlebotomist for the genomic assay. Additional tubes of blood will be concurrently collected and biobanked. This will eventually allow for immune profiling, Dr. Labkoff said.
Future goals include a patient-reported outcomes module and the ability to link data with medical claims.
So far, 79 patients have participated in the pilot program, according to the MMRF. As the database builds, Ms. Quinn Young and Dr. Labkoff anticipate that it will yield answers to a variety of real-world questions.
Dr. Labkoff offered two examples. “Of all the patients who have been exposed to ‘name your drug,’ what were the costs of their therapy, and what were the outcomes?” he said. In addition, researchers will be able to query clinical trial inclusion criteria to search for data on a specific patient profile, such as patients with a 4:14 translocation, who have had a bone marrow transplant in the last 2 years, and have been exposed to a certain drug regimen.
Ms. Quinn Young noted that doctors may be able to use the database to reliably identify high-risk patients and guide agent selection. Common patient questions also will be addressed, she said, including best treatment regimens for certain types of patients.
“For patients who may have run out of all commercially available options, or for patients who are perhaps seen at a community center, where certainly this type of profiling is not standard, it’s opening up a whole new set of options for them,” Ms. Quinn Young said. “And if their physician doesn’t pursue those options, they have the report that they can use to seek a second opinion.”
The Direct-to-Patient registry is unique because it aims to empower patients in a way that hasn’t been done before, Ms. Quinn Young said. “We are committed ... ever since we conceived of this project, to giving results back to patients. That is disruptive because right now that doesn’t exist.”
But the cost of implementing the registry, which has an approximate budget of $20 million, stands in the way of a completely free flow of anonymized data. MMRF leaders are exploring different strategies to sustain funding for the program.
Another MMRF program, CoMMpass, uses a precompetitive consortium model, in which several pharmaceutical companies pay for a preview of the data 6 months in advance of nonprofit researchers. A similar model may be used with the Direct-to-Patient registry, but this has yet to be determined, according to Dr. Labkoff and Ms. Quinn Young.
For now, Ms. Quinn Young said she hopes that physicians will be receptive to the program. “[The short term goal is that] when patients come to their doctors asking about this, that there is support and open-mindedness,” she said.
Looking to the future, Dr. Labkoff described how the registry could accelerate myeloma research, ultimately toward a cure.
“It is generally accepted that it can take 17 years to get something – a therapy, a new drug, or a guideline – from the bench to the bedside,” he said. “It’s my hope that we can take next generation sequencing and the results of this registry and bend that curve, maybe ... to 10 [years], or very aggressively, to 7 or 5 [years], where doctors are able to use the information in these reports for the patients that have literally given themselves, and use this to help guide the choices of their therapy or the trials they apply for, to help them get a better outcome in general.”
The Direct-to-Patient registry is a collaborative effort between the MMRF and multiple organizations, including the health care technology company COTA, the Broad Institute of Harvard and MIT, Prometheus Research, Tempus, and the Dana Farber Cancer Institute.
The Multiple Myeloma Research Foundation (MMRF) recently launched its Direct-to-Patient registry, in what the organization’s leaders are describing as a “disruptive” step toward improving outcomes for patients with multiple myeloma.
The new registry is intended to build upon CoMMpass, a program started 8 years ago that now represents the largest genomic database of any type of cancer. Although CoMMpass includes data from about 1,150 patients with myeloma, it’s not enough information, according to the chief marketing and development officer at the MMRF, Anne Quinn Young.
“For a disease as heterogenous as myeloma is, we need more, particularly because we don’t have all the samples for later-stage disease,” Ms. Quinn Young said in an interview. “And even with the clinical data, given the patient population, both [in terms of] demographics and the nature of the disease, the numbers of patients still living after multiple relapses is rather small.”
In an earlier effort to gather more data, the MMRF first turned to other organizations for help, but this approach fell short because of scarcity of data, and in some cases, unwillingness to share. Steven Labkoff, MD, chief data officer at the MMRF, described this experience in an interview.
“When the MMRF was looking around for different data sources for myeloma data, it was always the claim that, ‘Sure, we have plenty of patients, we have plenty of data, and it’s rich and really complete.’ However, as we approached an array of organizations – big organizations – as we dug into the details and reviewed patient counts or data completeness, they either didn’t have a sufficient number of patients, they didn’t have sufficiently complete data for our needs, and in the case where some did have sufficient numbers and complete data sets, they simply weren’t in a position to share that data outside their institution,” Dr. Labkoff said.
Undeterred, the MMRF switched tactics to the current, patient-centric approach.
“We’re leveraging one aspect of the HIPAA legislation,” Dr. Labkoff said, referring to patients’ rights to request their own medical records and an institution’s legal obligation to provide those records.
In the short-term, the registry will collect three types of data: patient donated data (answers from a patient survey), electronic medical records abstracted from all relevant past providers, and genomic test results. Participating patients will have blood drawn at home by a phlebotomist for the genomic assay. Additional tubes of blood will be concurrently collected and biobanked. This will eventually allow for immune profiling, Dr. Labkoff said.
Future goals include a patient-reported outcomes module and the ability to link data with medical claims.
So far, 79 patients have participated in the pilot program, according to the MMRF. As the database builds, Ms. Quinn Young and Dr. Labkoff anticipate that it will yield answers to a variety of real-world questions.
Dr. Labkoff offered two examples. “Of all the patients who have been exposed to ‘name your drug,’ what were the costs of their therapy, and what were the outcomes?” he said. In addition, researchers will be able to query clinical trial inclusion criteria to search for data on a specific patient profile, such as patients with a 4:14 translocation, who have had a bone marrow transplant in the last 2 years, and have been exposed to a certain drug regimen.
Ms. Quinn Young noted that doctors may be able to use the database to reliably identify high-risk patients and guide agent selection. Common patient questions also will be addressed, she said, including best treatment regimens for certain types of patients.
“For patients who may have run out of all commercially available options, or for patients who are perhaps seen at a community center, where certainly this type of profiling is not standard, it’s opening up a whole new set of options for them,” Ms. Quinn Young said. “And if their physician doesn’t pursue those options, they have the report that they can use to seek a second opinion.”
The Direct-to-Patient registry is unique because it aims to empower patients in a way that hasn’t been done before, Ms. Quinn Young said. “We are committed ... ever since we conceived of this project, to giving results back to patients. That is disruptive because right now that doesn’t exist.”
But the cost of implementing the registry, which has an approximate budget of $20 million, stands in the way of a completely free flow of anonymized data. MMRF leaders are exploring different strategies to sustain funding for the program.
Another MMRF program, CoMMpass, uses a precompetitive consortium model, in which several pharmaceutical companies pay for a preview of the data 6 months in advance of nonprofit researchers. A similar model may be used with the Direct-to-Patient registry, but this has yet to be determined, according to Dr. Labkoff and Ms. Quinn Young.
For now, Ms. Quinn Young said she hopes that physicians will be receptive to the program. “[The short term goal is that] when patients come to their doctors asking about this, that there is support and open-mindedness,” she said.
Looking to the future, Dr. Labkoff described how the registry could accelerate myeloma research, ultimately toward a cure.
“It is generally accepted that it can take 17 years to get something – a therapy, a new drug, or a guideline – from the bench to the bedside,” he said. “It’s my hope that we can take next generation sequencing and the results of this registry and bend that curve, maybe ... to 10 [years], or very aggressively, to 7 or 5 [years], where doctors are able to use the information in these reports for the patients that have literally given themselves, and use this to help guide the choices of their therapy or the trials they apply for, to help them get a better outcome in general.”
The Direct-to-Patient registry is a collaborative effort between the MMRF and multiple organizations, including the health care technology company COTA, the Broad Institute of Harvard and MIT, Prometheus Research, Tempus, and the Dana Farber Cancer Institute.
The Multiple Myeloma Research Foundation (MMRF) recently launched its Direct-to-Patient registry, in what the organization’s leaders are describing as a “disruptive” step toward improving outcomes for patients with multiple myeloma.
The new registry is intended to build upon CoMMpass, a program started 8 years ago that now represents the largest genomic database of any type of cancer. Although CoMMpass includes data from about 1,150 patients with myeloma, it’s not enough information, according to the chief marketing and development officer at the MMRF, Anne Quinn Young.
“For a disease as heterogenous as myeloma is, we need more, particularly because we don’t have all the samples for later-stage disease,” Ms. Quinn Young said in an interview. “And even with the clinical data, given the patient population, both [in terms of] demographics and the nature of the disease, the numbers of patients still living after multiple relapses is rather small.”
In an earlier effort to gather more data, the MMRF first turned to other organizations for help, but this approach fell short because of scarcity of data, and in some cases, unwillingness to share. Steven Labkoff, MD, chief data officer at the MMRF, described this experience in an interview.
“When the MMRF was looking around for different data sources for myeloma data, it was always the claim that, ‘Sure, we have plenty of patients, we have plenty of data, and it’s rich and really complete.’ However, as we approached an array of organizations – big organizations – as we dug into the details and reviewed patient counts or data completeness, they either didn’t have a sufficient number of patients, they didn’t have sufficiently complete data for our needs, and in the case where some did have sufficient numbers and complete data sets, they simply weren’t in a position to share that data outside their institution,” Dr. Labkoff said.
Undeterred, the MMRF switched tactics to the current, patient-centric approach.
“We’re leveraging one aspect of the HIPAA legislation,” Dr. Labkoff said, referring to patients’ rights to request their own medical records and an institution’s legal obligation to provide those records.
In the short-term, the registry will collect three types of data: patient donated data (answers from a patient survey), electronic medical records abstracted from all relevant past providers, and genomic test results. Participating patients will have blood drawn at home by a phlebotomist for the genomic assay. Additional tubes of blood will be concurrently collected and biobanked. This will eventually allow for immune profiling, Dr. Labkoff said.
Future goals include a patient-reported outcomes module and the ability to link data with medical claims.
So far, 79 patients have participated in the pilot program, according to the MMRF. As the database builds, Ms. Quinn Young and Dr. Labkoff anticipate that it will yield answers to a variety of real-world questions.
Dr. Labkoff offered two examples. “Of all the patients who have been exposed to ‘name your drug,’ what were the costs of their therapy, and what were the outcomes?” he said. In addition, researchers will be able to query clinical trial inclusion criteria to search for data on a specific patient profile, such as patients with a 4:14 translocation, who have had a bone marrow transplant in the last 2 years, and have been exposed to a certain drug regimen.
Ms. Quinn Young noted that doctors may be able to use the database to reliably identify high-risk patients and guide agent selection. Common patient questions also will be addressed, she said, including best treatment regimens for certain types of patients.
“For patients who may have run out of all commercially available options, or for patients who are perhaps seen at a community center, where certainly this type of profiling is not standard, it’s opening up a whole new set of options for them,” Ms. Quinn Young said. “And if their physician doesn’t pursue those options, they have the report that they can use to seek a second opinion.”
The Direct-to-Patient registry is unique because it aims to empower patients in a way that hasn’t been done before, Ms. Quinn Young said. “We are committed ... ever since we conceived of this project, to giving results back to patients. That is disruptive because right now that doesn’t exist.”
But the cost of implementing the registry, which has an approximate budget of $20 million, stands in the way of a completely free flow of anonymized data. MMRF leaders are exploring different strategies to sustain funding for the program.
Another MMRF program, CoMMpass, uses a precompetitive consortium model, in which several pharmaceutical companies pay for a preview of the data 6 months in advance of nonprofit researchers. A similar model may be used with the Direct-to-Patient registry, but this has yet to be determined, according to Dr. Labkoff and Ms. Quinn Young.
For now, Ms. Quinn Young said she hopes that physicians will be receptive to the program. “[The short term goal is that] when patients come to their doctors asking about this, that there is support and open-mindedness,” she said.
Looking to the future, Dr. Labkoff described how the registry could accelerate myeloma research, ultimately toward a cure.
“It is generally accepted that it can take 17 years to get something – a therapy, a new drug, or a guideline – from the bench to the bedside,” he said. “It’s my hope that we can take next generation sequencing and the results of this registry and bend that curve, maybe ... to 10 [years], or very aggressively, to 7 or 5 [years], where doctors are able to use the information in these reports for the patients that have literally given themselves, and use this to help guide the choices of their therapy or the trials they apply for, to help them get a better outcome in general.”
The Direct-to-Patient registry is a collaborative effort between the MMRF and multiple organizations, including the health care technology company COTA, the Broad Institute of Harvard and MIT, Prometheus Research, Tempus, and the Dana Farber Cancer Institute.
ATTEST: AFib ablation slows progression to persistence
PARIS – Radiofrequency catheter ablation of atrial fibrillation is not only a more definitive rhythm control treatment than antiarrhythmic drugs, but it’s also much more effective at slowing progression of AFib from paroxysmal to persistent, according to results from a randomized trial in 255 patients.
The multicenter study, ATTEST, randomized patients with paroxysmal AFib to radiofrequency catheter ablation or medical management and found that, during up to 3 years of follow-up, ablation cut the incidence of progression to persistent AFib by 89%, compared with medically managed patients, a statistically significant difference that documented a previously unappreciated benefit of catheter ablation: the ability to slow AFib progression, Karl-Heinz Kuck, MD, said at the annual congress of the European Society of Cardiology.
“This was never looked at before.” Assessing progression to persistent AFib is “a new endpoint for ablation” and an important one because progression from paroxysmal to persistent AFib has been associated with increased mortality, increased strokes, and increased hospitalizations,” said Dr. Kuck, a professor and cardiologist at the Asklepios Clinic St. Georg in Hamburg, Germany. If the findings are confirmed, “it may introduce a new indication for catheter ablation” in patients with paroxysmal AFib, Dr. Kuck said in an interview.
ATTEST (Atrial Fibrillation Progression Trial) enrolled patients at 30 sites worldwide who were at least 60 years old, had been diagnosed with paroxysmal AFib for at least 2 years, had at least two AFib episodes within 6 months of enrollment, and had not fully responded to one or two rhythm- or rate-control drugs. The 255 patients enrolled averaged 68 years of age, 58% were women, their median duration of AFib was slightly greater than 4 years, and on average patients had six to seven episodes during the prior 6 months. Enrollment into the study stopped sooner than planned because of slow recruitment, which topped out at 79% of the goal. Enrolled patients underwent weekly screening by transtelephonic monitoring for an AFib episode of at least 30 seconds during 3-9 months after entry, and then they had monthly screening. Patients positive for AFib on screening underwent a week of daily transtelephonic monitoring to determine whether their AFib persisted. The study’s primary endpoint was development of an AFib episode that lasted at least 7 days or for at least 2 days followed by cardioversion, which the investigators defined as persistent AFib.
The results showed that after 1 year development of persistent AFib occurred in 1% of the 128 patients assigned to receive ablation (102 actually underwent ablation) and in 7% of 127 patients assigned to drug management, with 123 patients who followed the treatment protocol. After 2 years of follow-up, the cumulative rate of progression to persistent AFib was 2% after ablation and 12% with medical treatment, and after 3 years, the respective rates of progression were 2% and 18%. The between-group differences were statistically significant at all three follow-up intervals, Dr. Kuck reported. Analysis of only patients who followed their assigned protocol showed similar results, as did an analysis that used the definition of persistent AFib advanced by the Heart Rhythm Society in 2017 (Heart Rhythm. 2017 Oct;14[10]:e275-e444).
The advantage of ablation for deferring progression was consistent in all subgroups analyzed, with no signal of interaction by age, sex, or other subgroup definitions. The rate of serious adverse events was “low,” occurring in 12% of the ablated patients and in 5% of controls. The need for two or more ablations was also “low,” Dr Kuck said, with 17% of patients requiring a second procedure. The results additionally showed that ablation also led to a lower rate of any AFib recurrence, regardless of whether or not it met the definition of persistent AFib. Any AFib recurrence occurred in 57% of the ablated patients and in 85% of those managed medically during 3 years of follow-up, a statistically significant difference.
Although the mechanism by which ablation slowed AFib progression is not known, Dr. Kuck suggested that it may relate to a reduction in the frequency and duration of AFib recurrences. “I believe that AFib burden is the key. If AFib episodes last a few days, then the likelihood of progressing to episodes that last 7 days is much higher than when an episode only lasts a few minutes,” he explained. “We’re opening a new perspective that looks beyond managing AFib symptoms” using ablation.
ATTEST was funded by Biosense Webster, a company that markets catheter ablation devices. Dr. Kuck has been a consultant to Biosense Webster, as well as to Abbott, Boston Scientific, Edwards, and Medtronic.
The ATTEST design and results are important because the study’s findings provide a good complement to the previously reported outcomes from the CASTLE-AF study, which randomized 363 patients with mostly persistent AFib (and heart failure) to catheter ablation of the AFib or medical management. The CASTLE-HF results showed that ablation was much more effective for reducing death from any cause and heart failure hospitalizations (N Engl J Med. 2018 Feb 1;378[5]:417-27). In other words, catheter ablation was the superior treatment for persistent AFib, the type of AFib diagnosed in about two-thirds of the patients enrolled in CASTLE-AF.
Thorsten Lewalter, MD, an arrhythmia specialist and professor at Peter Osypka Heart Center in Munich, made these comments in an interview. He has received personal fees from Abbott, Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, and Pfizer.
The ATTEST design and results are important because the study’s findings provide a good complement to the previously reported outcomes from the CASTLE-AF study, which randomized 363 patients with mostly persistent AFib (and heart failure) to catheter ablation of the AFib or medical management. The CASTLE-HF results showed that ablation was much more effective for reducing death from any cause and heart failure hospitalizations (N Engl J Med. 2018 Feb 1;378[5]:417-27). In other words, catheter ablation was the superior treatment for persistent AFib, the type of AFib diagnosed in about two-thirds of the patients enrolled in CASTLE-AF.
Thorsten Lewalter, MD, an arrhythmia specialist and professor at Peter Osypka Heart Center in Munich, made these comments in an interview. He has received personal fees from Abbott, Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, and Pfizer.
The ATTEST design and results are important because the study’s findings provide a good complement to the previously reported outcomes from the CASTLE-AF study, which randomized 363 patients with mostly persistent AFib (and heart failure) to catheter ablation of the AFib or medical management. The CASTLE-HF results showed that ablation was much more effective for reducing death from any cause and heart failure hospitalizations (N Engl J Med. 2018 Feb 1;378[5]:417-27). In other words, catheter ablation was the superior treatment for persistent AFib, the type of AFib diagnosed in about two-thirds of the patients enrolled in CASTLE-AF.
Thorsten Lewalter, MD, an arrhythmia specialist and professor at Peter Osypka Heart Center in Munich, made these comments in an interview. He has received personal fees from Abbott, Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, and Pfizer.
PARIS – Radiofrequency catheter ablation of atrial fibrillation is not only a more definitive rhythm control treatment than antiarrhythmic drugs, but it’s also much more effective at slowing progression of AFib from paroxysmal to persistent, according to results from a randomized trial in 255 patients.
The multicenter study, ATTEST, randomized patients with paroxysmal AFib to radiofrequency catheter ablation or medical management and found that, during up to 3 years of follow-up, ablation cut the incidence of progression to persistent AFib by 89%, compared with medically managed patients, a statistically significant difference that documented a previously unappreciated benefit of catheter ablation: the ability to slow AFib progression, Karl-Heinz Kuck, MD, said at the annual congress of the European Society of Cardiology.
“This was never looked at before.” Assessing progression to persistent AFib is “a new endpoint for ablation” and an important one because progression from paroxysmal to persistent AFib has been associated with increased mortality, increased strokes, and increased hospitalizations,” said Dr. Kuck, a professor and cardiologist at the Asklepios Clinic St. Georg in Hamburg, Germany. If the findings are confirmed, “it may introduce a new indication for catheter ablation” in patients with paroxysmal AFib, Dr. Kuck said in an interview.
ATTEST (Atrial Fibrillation Progression Trial) enrolled patients at 30 sites worldwide who were at least 60 years old, had been diagnosed with paroxysmal AFib for at least 2 years, had at least two AFib episodes within 6 months of enrollment, and had not fully responded to one or two rhythm- or rate-control drugs. The 255 patients enrolled averaged 68 years of age, 58% were women, their median duration of AFib was slightly greater than 4 years, and on average patients had six to seven episodes during the prior 6 months. Enrollment into the study stopped sooner than planned because of slow recruitment, which topped out at 79% of the goal. Enrolled patients underwent weekly screening by transtelephonic monitoring for an AFib episode of at least 30 seconds during 3-9 months after entry, and then they had monthly screening. Patients positive for AFib on screening underwent a week of daily transtelephonic monitoring to determine whether their AFib persisted. The study’s primary endpoint was development of an AFib episode that lasted at least 7 days or for at least 2 days followed by cardioversion, which the investigators defined as persistent AFib.
The results showed that after 1 year development of persistent AFib occurred in 1% of the 128 patients assigned to receive ablation (102 actually underwent ablation) and in 7% of 127 patients assigned to drug management, with 123 patients who followed the treatment protocol. After 2 years of follow-up, the cumulative rate of progression to persistent AFib was 2% after ablation and 12% with medical treatment, and after 3 years, the respective rates of progression were 2% and 18%. The between-group differences were statistically significant at all three follow-up intervals, Dr. Kuck reported. Analysis of only patients who followed their assigned protocol showed similar results, as did an analysis that used the definition of persistent AFib advanced by the Heart Rhythm Society in 2017 (Heart Rhythm. 2017 Oct;14[10]:e275-e444).
The advantage of ablation for deferring progression was consistent in all subgroups analyzed, with no signal of interaction by age, sex, or other subgroup definitions. The rate of serious adverse events was “low,” occurring in 12% of the ablated patients and in 5% of controls. The need for two or more ablations was also “low,” Dr Kuck said, with 17% of patients requiring a second procedure. The results additionally showed that ablation also led to a lower rate of any AFib recurrence, regardless of whether or not it met the definition of persistent AFib. Any AFib recurrence occurred in 57% of the ablated patients and in 85% of those managed medically during 3 years of follow-up, a statistically significant difference.
Although the mechanism by which ablation slowed AFib progression is not known, Dr. Kuck suggested that it may relate to a reduction in the frequency and duration of AFib recurrences. “I believe that AFib burden is the key. If AFib episodes last a few days, then the likelihood of progressing to episodes that last 7 days is much higher than when an episode only lasts a few minutes,” he explained. “We’re opening a new perspective that looks beyond managing AFib symptoms” using ablation.
ATTEST was funded by Biosense Webster, a company that markets catheter ablation devices. Dr. Kuck has been a consultant to Biosense Webster, as well as to Abbott, Boston Scientific, Edwards, and Medtronic.
PARIS – Radiofrequency catheter ablation of atrial fibrillation is not only a more definitive rhythm control treatment than antiarrhythmic drugs, but it’s also much more effective at slowing progression of AFib from paroxysmal to persistent, according to results from a randomized trial in 255 patients.
The multicenter study, ATTEST, randomized patients with paroxysmal AFib to radiofrequency catheter ablation or medical management and found that, during up to 3 years of follow-up, ablation cut the incidence of progression to persistent AFib by 89%, compared with medically managed patients, a statistically significant difference that documented a previously unappreciated benefit of catheter ablation: the ability to slow AFib progression, Karl-Heinz Kuck, MD, said at the annual congress of the European Society of Cardiology.
“This was never looked at before.” Assessing progression to persistent AFib is “a new endpoint for ablation” and an important one because progression from paroxysmal to persistent AFib has been associated with increased mortality, increased strokes, and increased hospitalizations,” said Dr. Kuck, a professor and cardiologist at the Asklepios Clinic St. Georg in Hamburg, Germany. If the findings are confirmed, “it may introduce a new indication for catheter ablation” in patients with paroxysmal AFib, Dr. Kuck said in an interview.
ATTEST (Atrial Fibrillation Progression Trial) enrolled patients at 30 sites worldwide who were at least 60 years old, had been diagnosed with paroxysmal AFib for at least 2 years, had at least two AFib episodes within 6 months of enrollment, and had not fully responded to one or two rhythm- or rate-control drugs. The 255 patients enrolled averaged 68 years of age, 58% were women, their median duration of AFib was slightly greater than 4 years, and on average patients had six to seven episodes during the prior 6 months. Enrollment into the study stopped sooner than planned because of slow recruitment, which topped out at 79% of the goal. Enrolled patients underwent weekly screening by transtelephonic monitoring for an AFib episode of at least 30 seconds during 3-9 months after entry, and then they had monthly screening. Patients positive for AFib on screening underwent a week of daily transtelephonic monitoring to determine whether their AFib persisted. The study’s primary endpoint was development of an AFib episode that lasted at least 7 days or for at least 2 days followed by cardioversion, which the investigators defined as persistent AFib.
The results showed that after 1 year development of persistent AFib occurred in 1% of the 128 patients assigned to receive ablation (102 actually underwent ablation) and in 7% of 127 patients assigned to drug management, with 123 patients who followed the treatment protocol. After 2 years of follow-up, the cumulative rate of progression to persistent AFib was 2% after ablation and 12% with medical treatment, and after 3 years, the respective rates of progression were 2% and 18%. The between-group differences were statistically significant at all three follow-up intervals, Dr. Kuck reported. Analysis of only patients who followed their assigned protocol showed similar results, as did an analysis that used the definition of persistent AFib advanced by the Heart Rhythm Society in 2017 (Heart Rhythm. 2017 Oct;14[10]:e275-e444).
The advantage of ablation for deferring progression was consistent in all subgroups analyzed, with no signal of interaction by age, sex, or other subgroup definitions. The rate of serious adverse events was “low,” occurring in 12% of the ablated patients and in 5% of controls. The need for two or more ablations was also “low,” Dr Kuck said, with 17% of patients requiring a second procedure. The results additionally showed that ablation also led to a lower rate of any AFib recurrence, regardless of whether or not it met the definition of persistent AFib. Any AFib recurrence occurred in 57% of the ablated patients and in 85% of those managed medically during 3 years of follow-up, a statistically significant difference.
Although the mechanism by which ablation slowed AFib progression is not known, Dr. Kuck suggested that it may relate to a reduction in the frequency and duration of AFib recurrences. “I believe that AFib burden is the key. If AFib episodes last a few days, then the likelihood of progressing to episodes that last 7 days is much higher than when an episode only lasts a few minutes,” he explained. “We’re opening a new perspective that looks beyond managing AFib symptoms” using ablation.
ATTEST was funded by Biosense Webster, a company that markets catheter ablation devices. Dr. Kuck has been a consultant to Biosense Webster, as well as to Abbott, Boston Scientific, Edwards, and Medtronic.
REPORTING FROM THE ESC 2019 CONGRESS
Short Takes
E-cigarettes with behavioral support more effective than nicotine replacement for smoking cessation
A study of 886 randomized United Kingdom National Health Service stop-smoking service attendees showed better 1-year abstinence rates in the e-cigarette (18%) vs. nicotine replacement product (9%) group (risk ratio,1.83; 95% confidence interval, 1.30-2.58) when both groups received behavioral support.
Citation: Hajek P et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Eng J Med. 2019 Feb 14;380:629-37.
New scoring system more accurate in diagnosing sepsis than qSOFA
Using retrospective data from 2,759,529 ED patients in 49 urban hospitals, and a supervised machine-learning process, the authors developed a Risk of Sepsis score, which demonstrated significantly higher sensitivity for detecting sepsis than the qSOFA (Quick Sequential Organ Failure Assessment) score.
Citation: Delahanty R et al. Development and evaluation of a machine learning model for the early identification of patients at risk for sepsis. Ann Emerg Med. 2019 Apr;73(4):334-44.
Shared decision making may decrease risk of legal action
A randomized, controlled simulation experiment using a clinical vignette with an adverse outcome showed that when engaged in shared decision making, participants were less likely to consider taking legal action.
Citation: Schoenfeld EM et al. The effect of shared decision making on patients’ likelihood of filing a complaint or lawsuit: A simulation study. Ann Emerg Med. 2019 Jan 3. doi: 10.1016/j.annemergmed.2018.11.017.
ADA issues new inpatient diabetes care recommendations
The American Diabetes Association recommends that insulin therapy be initiated for a majority of inpatients who have persistent hyperglycemia greater than 180 mg/dL to target a blood glucose range of 140-180 mg/dL. They recommend the use of basal insulin or basal plus bolus insulin and discourage the sole use of sliding scale insulin.
Citation: American Diabetes Association. 15. Diabetes care in the hospital: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl. 1):S173-81.
Beta-blocker use may reduce risk of COPD hospitalization
In a retrospective longitudinal study of 301,542 patients newly prescribed beta-blockers and 1,000,633 patients newly prescribed any other antihypertensive drug, patients who were treated with beta-blockers continuously for more than 6 months had a significantly lower risk of chronic obstructive pulmonary disease (COPD) hospitalization, all-cause mortality, and COPD death than did patients who received alternative antihypertensives. Patients with a history of COPD hospitalization were excluded from this study.
Citation: Nielsen AO et al. Beta-blocker therapy and risk of chronic obstructive pulmonary disease: A Danish nationwide study of 1.3 million individuals. EClinicalMedicine. 2019;7:21-6. doi: 10.1016/j.eclinm.2019.01.004.
E-cigarettes with behavioral support more effective than nicotine replacement for smoking cessation
A study of 886 randomized United Kingdom National Health Service stop-smoking service attendees showed better 1-year abstinence rates in the e-cigarette (18%) vs. nicotine replacement product (9%) group (risk ratio,1.83; 95% confidence interval, 1.30-2.58) when both groups received behavioral support.
Citation: Hajek P et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Eng J Med. 2019 Feb 14;380:629-37.
New scoring system more accurate in diagnosing sepsis than qSOFA
Using retrospective data from 2,759,529 ED patients in 49 urban hospitals, and a supervised machine-learning process, the authors developed a Risk of Sepsis score, which demonstrated significantly higher sensitivity for detecting sepsis than the qSOFA (Quick Sequential Organ Failure Assessment) score.
Citation: Delahanty R et al. Development and evaluation of a machine learning model for the early identification of patients at risk for sepsis. Ann Emerg Med. 2019 Apr;73(4):334-44.
Shared decision making may decrease risk of legal action
A randomized, controlled simulation experiment using a clinical vignette with an adverse outcome showed that when engaged in shared decision making, participants were less likely to consider taking legal action.
Citation: Schoenfeld EM et al. The effect of shared decision making on patients’ likelihood of filing a complaint or lawsuit: A simulation study. Ann Emerg Med. 2019 Jan 3. doi: 10.1016/j.annemergmed.2018.11.017.
ADA issues new inpatient diabetes care recommendations
The American Diabetes Association recommends that insulin therapy be initiated for a majority of inpatients who have persistent hyperglycemia greater than 180 mg/dL to target a blood glucose range of 140-180 mg/dL. They recommend the use of basal insulin or basal plus bolus insulin and discourage the sole use of sliding scale insulin.
Citation: American Diabetes Association. 15. Diabetes care in the hospital: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl. 1):S173-81.
Beta-blocker use may reduce risk of COPD hospitalization
In a retrospective longitudinal study of 301,542 patients newly prescribed beta-blockers and 1,000,633 patients newly prescribed any other antihypertensive drug, patients who were treated with beta-blockers continuously for more than 6 months had a significantly lower risk of chronic obstructive pulmonary disease (COPD) hospitalization, all-cause mortality, and COPD death than did patients who received alternative antihypertensives. Patients with a history of COPD hospitalization were excluded from this study.
Citation: Nielsen AO et al. Beta-blocker therapy and risk of chronic obstructive pulmonary disease: A Danish nationwide study of 1.3 million individuals. EClinicalMedicine. 2019;7:21-6. doi: 10.1016/j.eclinm.2019.01.004.
E-cigarettes with behavioral support more effective than nicotine replacement for smoking cessation
A study of 886 randomized United Kingdom National Health Service stop-smoking service attendees showed better 1-year abstinence rates in the e-cigarette (18%) vs. nicotine replacement product (9%) group (risk ratio,1.83; 95% confidence interval, 1.30-2.58) when both groups received behavioral support.
Citation: Hajek P et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Eng J Med. 2019 Feb 14;380:629-37.
New scoring system more accurate in diagnosing sepsis than qSOFA
Using retrospective data from 2,759,529 ED patients in 49 urban hospitals, and a supervised machine-learning process, the authors developed a Risk of Sepsis score, which demonstrated significantly higher sensitivity for detecting sepsis than the qSOFA (Quick Sequential Organ Failure Assessment) score.
Citation: Delahanty R et al. Development and evaluation of a machine learning model for the early identification of patients at risk for sepsis. Ann Emerg Med. 2019 Apr;73(4):334-44.
Shared decision making may decrease risk of legal action
A randomized, controlled simulation experiment using a clinical vignette with an adverse outcome showed that when engaged in shared decision making, participants were less likely to consider taking legal action.
Citation: Schoenfeld EM et al. The effect of shared decision making on patients’ likelihood of filing a complaint or lawsuit: A simulation study. Ann Emerg Med. 2019 Jan 3. doi: 10.1016/j.annemergmed.2018.11.017.
ADA issues new inpatient diabetes care recommendations
The American Diabetes Association recommends that insulin therapy be initiated for a majority of inpatients who have persistent hyperglycemia greater than 180 mg/dL to target a blood glucose range of 140-180 mg/dL. They recommend the use of basal insulin or basal plus bolus insulin and discourage the sole use of sliding scale insulin.
Citation: American Diabetes Association. 15. Diabetes care in the hospital: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl. 1):S173-81.
Beta-blocker use may reduce risk of COPD hospitalization
In a retrospective longitudinal study of 301,542 patients newly prescribed beta-blockers and 1,000,633 patients newly prescribed any other antihypertensive drug, patients who were treated with beta-blockers continuously for more than 6 months had a significantly lower risk of chronic obstructive pulmonary disease (COPD) hospitalization, all-cause mortality, and COPD death than did patients who received alternative antihypertensives. Patients with a history of COPD hospitalization were excluded from this study.
Citation: Nielsen AO et al. Beta-blocker therapy and risk of chronic obstructive pulmonary disease: A Danish nationwide study of 1.3 million individuals. EClinicalMedicine. 2019;7:21-6. doi: 10.1016/j.eclinm.2019.01.004.
Combo produces disappointing PFS, promising OS in metastatic colorectal cancer
NATIONAL HARBOR, MD. – An immunochemotherapy regimen produced mixed results in a phase 2 trial of patients with previously untreated metastatic colorectal cancer.
The regimen – avelumab and cetuximab plus oxaliplatin, leucovorin, and 5-fluorouracil (mFOLFOX6) – failed to meet the primary endpoint for progression-free survival (PFS) but was associated with “promising” yet “preliminary” overall survival, according to Joseph Tintelnot, MD, of University Medical Center Hamburg-Eppendorf (Germany).
Dr. Tintelnot presented these results from the AVETUX trial (NCT03174405) at the annual meeting of the Society for Immunotherapy of Cancer.
The trial enrolled 43 patients with previously untreated, metastatic colorectal cancer, and 39 of them had wild-type RAS and BRAF mutations. Among those 39 patients, the median age was 62 years (range, 29-82 years), 13 patients were female, and 36 patients had left-sided tumors.
A total of 30 patients had liver metastasis, 12 had lung metastasis, and 18 had lymph node metastasis. Most patients (n = 36) had microsatellite stable tumors, 2 were microsatellite instability high, and 1 was microsatellite instability low.
Patients received IV cetuximab at 250 mg/m2 over 60-90 minutes (day 1 and 8), with a first dose of 400 mg/m2; mFOLFOX6 according to local standard – IV oxaliplatin at 85 mg/m2 IV (day 1), IV leucovorin at 400 mg/m2 IV (day 1), and IV bolus 5-fluorouracil at 400 mg/m2 (day 1) and IV at 2,400 mg/m2 (days 1-3); and IV avelumab at 10 mg/kg over 60-90 minutes (day 1 from cycle 2 onward).
The median number of treatment cycles was 8 (range, 1-34) for oxaliplatin, 13 (range, 1-35) for 5-fluorouracil, 12 (range, 1-35) for cetuximab, and 16 (range, 0-34) for avelumab. The median duration of cetuximab/avelumab treatment was 5.4 months (range, 0.7-18.4 months).
The study’s primary endpoint was 12-month PFS, and the researchers expected the PFS to rise from 40% to 57%. Unfortunately, the 12-month PFS was 40%, so the primary endpoint was not met.
However, the treatment produced a “very high” overall response rate at 81% (30/37), according to Dr. Tintelnot. A total of 4 patients achieved a complete response, 26 had a partial response, 4 had stable disease, and 3 progressed.
Dr. Tintelnot also noted a “promising” but “preliminary” overall survival rate – 84% at a median follow-up of 16.2 months. He said these results suggest PFS may not be the ideal endpoint for this combination.
Dr. Tintelnot said the combination was safe, with no unexpected toxicities. The most common grade 3-4 adverse events were infection of catheter, device, urinary tract, etc. (32%); abdominal pain, diarrhea, etc. (24%); skin reaction (21%); anemia, blood disorders, and hemolytic-uremic syndrome (18%); administration, infusion-related, and allergic reactions (16%); cognitive disturbance, meningism, syncope, and psychiatric disorders (16%); and peripheral sensory polyneuropathy and paresthesia (16%).
Dr. Tintelnot and colleagues also conducted translational research evaluating programmed death-ligand 1 (PD-L1) expression and serial circulating tumor DNA in patients on this trial.
The team found no clear correlation between PFS and T-cell diversification, tumor-infiltrating lymphocytes, or tumor proportion score. Dr. Tintelnot said this suggests classical predictive factors for PD-1/PD-L1 inhibitor treatment have a limited role with this combination.
The researchers did find that circulating tumor mutations might help predict early relapse with the regimen. The team identified 26 patients with mutations detectable in their blood. There was an immediate decline of circulating tumor mutations after treatment initiation, and reemergence of mutation clones was associated with progression.
Lastly, the researchers found that avelumab, cetuximab, and mFOLFOX6 suppressed the development of epidermal growth factor receptor–resistant subclones. There were no epidermal growth factor receptor mutations detected during follow-up.
This research was sponsored by AIO-Studien-gGmbH. Dr. Tintelnot disclosed no conflicts of interest.
SOURCE: Tintelnot J et al. SITC 2019, Abstract O16.
NATIONAL HARBOR, MD. – An immunochemotherapy regimen produced mixed results in a phase 2 trial of patients with previously untreated metastatic colorectal cancer.
The regimen – avelumab and cetuximab plus oxaliplatin, leucovorin, and 5-fluorouracil (mFOLFOX6) – failed to meet the primary endpoint for progression-free survival (PFS) but was associated with “promising” yet “preliminary” overall survival, according to Joseph Tintelnot, MD, of University Medical Center Hamburg-Eppendorf (Germany).
Dr. Tintelnot presented these results from the AVETUX trial (NCT03174405) at the annual meeting of the Society for Immunotherapy of Cancer.
The trial enrolled 43 patients with previously untreated, metastatic colorectal cancer, and 39 of them had wild-type RAS and BRAF mutations. Among those 39 patients, the median age was 62 years (range, 29-82 years), 13 patients were female, and 36 patients had left-sided tumors.
A total of 30 patients had liver metastasis, 12 had lung metastasis, and 18 had lymph node metastasis. Most patients (n = 36) had microsatellite stable tumors, 2 were microsatellite instability high, and 1 was microsatellite instability low.
Patients received IV cetuximab at 250 mg/m2 over 60-90 minutes (day 1 and 8), with a first dose of 400 mg/m2; mFOLFOX6 according to local standard – IV oxaliplatin at 85 mg/m2 IV (day 1), IV leucovorin at 400 mg/m2 IV (day 1), and IV bolus 5-fluorouracil at 400 mg/m2 (day 1) and IV at 2,400 mg/m2 (days 1-3); and IV avelumab at 10 mg/kg over 60-90 minutes (day 1 from cycle 2 onward).
The median number of treatment cycles was 8 (range, 1-34) for oxaliplatin, 13 (range, 1-35) for 5-fluorouracil, 12 (range, 1-35) for cetuximab, and 16 (range, 0-34) for avelumab. The median duration of cetuximab/avelumab treatment was 5.4 months (range, 0.7-18.4 months).
The study’s primary endpoint was 12-month PFS, and the researchers expected the PFS to rise from 40% to 57%. Unfortunately, the 12-month PFS was 40%, so the primary endpoint was not met.
However, the treatment produced a “very high” overall response rate at 81% (30/37), according to Dr. Tintelnot. A total of 4 patients achieved a complete response, 26 had a partial response, 4 had stable disease, and 3 progressed.
Dr. Tintelnot also noted a “promising” but “preliminary” overall survival rate – 84% at a median follow-up of 16.2 months. He said these results suggest PFS may not be the ideal endpoint for this combination.
Dr. Tintelnot said the combination was safe, with no unexpected toxicities. The most common grade 3-4 adverse events were infection of catheter, device, urinary tract, etc. (32%); abdominal pain, diarrhea, etc. (24%); skin reaction (21%); anemia, blood disorders, and hemolytic-uremic syndrome (18%); administration, infusion-related, and allergic reactions (16%); cognitive disturbance, meningism, syncope, and psychiatric disorders (16%); and peripheral sensory polyneuropathy and paresthesia (16%).
Dr. Tintelnot and colleagues also conducted translational research evaluating programmed death-ligand 1 (PD-L1) expression and serial circulating tumor DNA in patients on this trial.
The team found no clear correlation between PFS and T-cell diversification, tumor-infiltrating lymphocytes, or tumor proportion score. Dr. Tintelnot said this suggests classical predictive factors for PD-1/PD-L1 inhibitor treatment have a limited role with this combination.
The researchers did find that circulating tumor mutations might help predict early relapse with the regimen. The team identified 26 patients with mutations detectable in their blood. There was an immediate decline of circulating tumor mutations after treatment initiation, and reemergence of mutation clones was associated with progression.
Lastly, the researchers found that avelumab, cetuximab, and mFOLFOX6 suppressed the development of epidermal growth factor receptor–resistant subclones. There were no epidermal growth factor receptor mutations detected during follow-up.
This research was sponsored by AIO-Studien-gGmbH. Dr. Tintelnot disclosed no conflicts of interest.
SOURCE: Tintelnot J et al. SITC 2019, Abstract O16.
NATIONAL HARBOR, MD. – An immunochemotherapy regimen produced mixed results in a phase 2 trial of patients with previously untreated metastatic colorectal cancer.
The regimen – avelumab and cetuximab plus oxaliplatin, leucovorin, and 5-fluorouracil (mFOLFOX6) – failed to meet the primary endpoint for progression-free survival (PFS) but was associated with “promising” yet “preliminary” overall survival, according to Joseph Tintelnot, MD, of University Medical Center Hamburg-Eppendorf (Germany).
Dr. Tintelnot presented these results from the AVETUX trial (NCT03174405) at the annual meeting of the Society for Immunotherapy of Cancer.
The trial enrolled 43 patients with previously untreated, metastatic colorectal cancer, and 39 of them had wild-type RAS and BRAF mutations. Among those 39 patients, the median age was 62 years (range, 29-82 years), 13 patients were female, and 36 patients had left-sided tumors.
A total of 30 patients had liver metastasis, 12 had lung metastasis, and 18 had lymph node metastasis. Most patients (n = 36) had microsatellite stable tumors, 2 were microsatellite instability high, and 1 was microsatellite instability low.
Patients received IV cetuximab at 250 mg/m2 over 60-90 minutes (day 1 and 8), with a first dose of 400 mg/m2; mFOLFOX6 according to local standard – IV oxaliplatin at 85 mg/m2 IV (day 1), IV leucovorin at 400 mg/m2 IV (day 1), and IV bolus 5-fluorouracil at 400 mg/m2 (day 1) and IV at 2,400 mg/m2 (days 1-3); and IV avelumab at 10 mg/kg over 60-90 minutes (day 1 from cycle 2 onward).
The median number of treatment cycles was 8 (range, 1-34) for oxaliplatin, 13 (range, 1-35) for 5-fluorouracil, 12 (range, 1-35) for cetuximab, and 16 (range, 0-34) for avelumab. The median duration of cetuximab/avelumab treatment was 5.4 months (range, 0.7-18.4 months).
The study’s primary endpoint was 12-month PFS, and the researchers expected the PFS to rise from 40% to 57%. Unfortunately, the 12-month PFS was 40%, so the primary endpoint was not met.
However, the treatment produced a “very high” overall response rate at 81% (30/37), according to Dr. Tintelnot. A total of 4 patients achieved a complete response, 26 had a partial response, 4 had stable disease, and 3 progressed.
Dr. Tintelnot also noted a “promising” but “preliminary” overall survival rate – 84% at a median follow-up of 16.2 months. He said these results suggest PFS may not be the ideal endpoint for this combination.
Dr. Tintelnot said the combination was safe, with no unexpected toxicities. The most common grade 3-4 adverse events were infection of catheter, device, urinary tract, etc. (32%); abdominal pain, diarrhea, etc. (24%); skin reaction (21%); anemia, blood disorders, and hemolytic-uremic syndrome (18%); administration, infusion-related, and allergic reactions (16%); cognitive disturbance, meningism, syncope, and psychiatric disorders (16%); and peripheral sensory polyneuropathy and paresthesia (16%).
Dr. Tintelnot and colleagues also conducted translational research evaluating programmed death-ligand 1 (PD-L1) expression and serial circulating tumor DNA in patients on this trial.
The team found no clear correlation between PFS and T-cell diversification, tumor-infiltrating lymphocytes, or tumor proportion score. Dr. Tintelnot said this suggests classical predictive factors for PD-1/PD-L1 inhibitor treatment have a limited role with this combination.
The researchers did find that circulating tumor mutations might help predict early relapse with the regimen. The team identified 26 patients with mutations detectable in their blood. There was an immediate decline of circulating tumor mutations after treatment initiation, and reemergence of mutation clones was associated with progression.
Lastly, the researchers found that avelumab, cetuximab, and mFOLFOX6 suppressed the development of epidermal growth factor receptor–resistant subclones. There were no epidermal growth factor receptor mutations detected during follow-up.
This research was sponsored by AIO-Studien-gGmbH. Dr. Tintelnot disclosed no conflicts of interest.
SOURCE: Tintelnot J et al. SITC 2019, Abstract O16.
REPORTING FROM SITC 2019
Disentangling sleep problems and bipolar disorder
COPENHAGEN – Sleep spindle density is diminished in euthymic patients with bipolar disorder, suggesting that this sleep architecture abnormality might offer potential for early differentiation of bipolar from unipolar depression, Philipp S. Ritter, MD, said at the annual congress of the European College of Neuropsychopharmacology.
“Hopefully in the future our finding, if replicated, might have clinical utility. It might be a kind of soft biomarker that could be used in early detection, or, in people having their first depressive episode, you could perhaps use this to risk-stratify. And if you see there’s a great reduction in spindle density then a patient might have a higher likelihood of a bipolar disorder, so you might not want to treat with antidepressants that have a high switch rate,” explained Dr. Ritter, a psychiatrist at Technical University of Dresden (Germany).
Sleep spindles are a specific sleep architecture formation evident on the sleep EEG. They are sudden high-amplitude bursts occurring in stage N2 sleep. They are thought to be associated with sensory gating and memory processes. Other investigators have repeatedly demonstrated that patients with schizophrenia, as well as their asymptomatic first-degree relatives, have a reduced density of fast spindles greater than 13 Hz, compared with the general population. In contrast, patients with unipolar depression do not display this polysomnographic abnormality.
These findings prompted Dr. Ritter and his coinvestigators to conduct an all-night polysomnographic study in 24 euthymic patients with bipolar disorder and 25 healthy controls. The bipolar patients demonstrated a reduced density and mean frequency of fast sleep spindles, but not slow spindles (Acta Psychiatr Scand. 2018 Aug;138[2]:163-72).
These sleep spindle findings implicate thalamic dysfunction as a potential neurobiologic mechanism in bipolar disorder, since spindles are generated in the thalamus and spun off in thalamocortical feedback loops, Dr. Ritter observed.
Which came first: the chicken (bipolar disorder) or the egg (sleep disturbance)?
Sleep problems are a prominent issue in patients with bipolar disorder, even when they are euthymic.
“Anybody who deals with bipolar patients knows that sleep is a constant issue. You are always talking to your patients about their sleep. They’re sleeping too much, or not enough, or they’re sleeping just about right but it’s unsatisfactory. They do not sleep well. And if there’s something that disrupts their sleep, it can precipitate episodes,” Dr. Ritter said.
He wondered whether sleep problems are an intrinsic part of the bipolar illness, or a byproduct of the stress of having a severe mental disorder, perhaps a medication side effect, or whether the disordered sleep actually precedes the clinical expression of the mood disorder. So he and his coinvestigators turned to a Munich-based cohort sample of 3,021 adolescents and young adults assessed via the standardized Composite International Diagnostic Interview four times during 10 years of prospective follow-up.
Among 1,943 participants in the epidemiologic study who were free of major mental disorders at entry, the presence of sleep disturbance at baseline as quantified using the Symptom Checklist-90-Revised doubled the risk of developing bipolar disorder within the next 10 years. After the researchers controlled for potential confounders, including parental mood disorder, gender, age, and a history of alcohol or cannabis dependence, poor sleep quality at baseline remained independently associated with a 1.75-fold increased chance of subsequently developing bipolar disorder (J Psychiatr Res. 2015 Sep;68:76-82).
“This is a little bit higher, actually, than the odds ratio usually found for depressive disorders,” said Dr. Ritter.
he added.
Dr. Ritter reported having no financial conflicts regarding these studies.
COPENHAGEN – Sleep spindle density is diminished in euthymic patients with bipolar disorder, suggesting that this sleep architecture abnormality might offer potential for early differentiation of bipolar from unipolar depression, Philipp S. Ritter, MD, said at the annual congress of the European College of Neuropsychopharmacology.
“Hopefully in the future our finding, if replicated, might have clinical utility. It might be a kind of soft biomarker that could be used in early detection, or, in people having their first depressive episode, you could perhaps use this to risk-stratify. And if you see there’s a great reduction in spindle density then a patient might have a higher likelihood of a bipolar disorder, so you might not want to treat with antidepressants that have a high switch rate,” explained Dr. Ritter, a psychiatrist at Technical University of Dresden (Germany).
Sleep spindles are a specific sleep architecture formation evident on the sleep EEG. They are sudden high-amplitude bursts occurring in stage N2 sleep. They are thought to be associated with sensory gating and memory processes. Other investigators have repeatedly demonstrated that patients with schizophrenia, as well as their asymptomatic first-degree relatives, have a reduced density of fast spindles greater than 13 Hz, compared with the general population. In contrast, patients with unipolar depression do not display this polysomnographic abnormality.
These findings prompted Dr. Ritter and his coinvestigators to conduct an all-night polysomnographic study in 24 euthymic patients with bipolar disorder and 25 healthy controls. The bipolar patients demonstrated a reduced density and mean frequency of fast sleep spindles, but not slow spindles (Acta Psychiatr Scand. 2018 Aug;138[2]:163-72).
These sleep spindle findings implicate thalamic dysfunction as a potential neurobiologic mechanism in bipolar disorder, since spindles are generated in the thalamus and spun off in thalamocortical feedback loops, Dr. Ritter observed.
Which came first: the chicken (bipolar disorder) or the egg (sleep disturbance)?
Sleep problems are a prominent issue in patients with bipolar disorder, even when they are euthymic.
“Anybody who deals with bipolar patients knows that sleep is a constant issue. You are always talking to your patients about their sleep. They’re sleeping too much, or not enough, or they’re sleeping just about right but it’s unsatisfactory. They do not sleep well. And if there’s something that disrupts their sleep, it can precipitate episodes,” Dr. Ritter said.
He wondered whether sleep problems are an intrinsic part of the bipolar illness, or a byproduct of the stress of having a severe mental disorder, perhaps a medication side effect, or whether the disordered sleep actually precedes the clinical expression of the mood disorder. So he and his coinvestigators turned to a Munich-based cohort sample of 3,021 adolescents and young adults assessed via the standardized Composite International Diagnostic Interview four times during 10 years of prospective follow-up.
Among 1,943 participants in the epidemiologic study who were free of major mental disorders at entry, the presence of sleep disturbance at baseline as quantified using the Symptom Checklist-90-Revised doubled the risk of developing bipolar disorder within the next 10 years. After the researchers controlled for potential confounders, including parental mood disorder, gender, age, and a history of alcohol or cannabis dependence, poor sleep quality at baseline remained independently associated with a 1.75-fold increased chance of subsequently developing bipolar disorder (J Psychiatr Res. 2015 Sep;68:76-82).
“This is a little bit higher, actually, than the odds ratio usually found for depressive disorders,” said Dr. Ritter.
he added.
Dr. Ritter reported having no financial conflicts regarding these studies.
COPENHAGEN – Sleep spindle density is diminished in euthymic patients with bipolar disorder, suggesting that this sleep architecture abnormality might offer potential for early differentiation of bipolar from unipolar depression, Philipp S. Ritter, MD, said at the annual congress of the European College of Neuropsychopharmacology.
“Hopefully in the future our finding, if replicated, might have clinical utility. It might be a kind of soft biomarker that could be used in early detection, or, in people having their first depressive episode, you could perhaps use this to risk-stratify. And if you see there’s a great reduction in spindle density then a patient might have a higher likelihood of a bipolar disorder, so you might not want to treat with antidepressants that have a high switch rate,” explained Dr. Ritter, a psychiatrist at Technical University of Dresden (Germany).
Sleep spindles are a specific sleep architecture formation evident on the sleep EEG. They are sudden high-amplitude bursts occurring in stage N2 sleep. They are thought to be associated with sensory gating and memory processes. Other investigators have repeatedly demonstrated that patients with schizophrenia, as well as their asymptomatic first-degree relatives, have a reduced density of fast spindles greater than 13 Hz, compared with the general population. In contrast, patients with unipolar depression do not display this polysomnographic abnormality.
These findings prompted Dr. Ritter and his coinvestigators to conduct an all-night polysomnographic study in 24 euthymic patients with bipolar disorder and 25 healthy controls. The bipolar patients demonstrated a reduced density and mean frequency of fast sleep spindles, but not slow spindles (Acta Psychiatr Scand. 2018 Aug;138[2]:163-72).
These sleep spindle findings implicate thalamic dysfunction as a potential neurobiologic mechanism in bipolar disorder, since spindles are generated in the thalamus and spun off in thalamocortical feedback loops, Dr. Ritter observed.
Which came first: the chicken (bipolar disorder) or the egg (sleep disturbance)?
Sleep problems are a prominent issue in patients with bipolar disorder, even when they are euthymic.
“Anybody who deals with bipolar patients knows that sleep is a constant issue. You are always talking to your patients about their sleep. They’re sleeping too much, or not enough, or they’re sleeping just about right but it’s unsatisfactory. They do not sleep well. And if there’s something that disrupts their sleep, it can precipitate episodes,” Dr. Ritter said.
He wondered whether sleep problems are an intrinsic part of the bipolar illness, or a byproduct of the stress of having a severe mental disorder, perhaps a medication side effect, or whether the disordered sleep actually precedes the clinical expression of the mood disorder. So he and his coinvestigators turned to a Munich-based cohort sample of 3,021 adolescents and young adults assessed via the standardized Composite International Diagnostic Interview four times during 10 years of prospective follow-up.
Among 1,943 participants in the epidemiologic study who were free of major mental disorders at entry, the presence of sleep disturbance at baseline as quantified using the Symptom Checklist-90-Revised doubled the risk of developing bipolar disorder within the next 10 years. After the researchers controlled for potential confounders, including parental mood disorder, gender, age, and a history of alcohol or cannabis dependence, poor sleep quality at baseline remained independently associated with a 1.75-fold increased chance of subsequently developing bipolar disorder (J Psychiatr Res. 2015 Sep;68:76-82).
“This is a little bit higher, actually, than the odds ratio usually found for depressive disorders,” said Dr. Ritter.
he added.
Dr. Ritter reported having no financial conflicts regarding these studies.
REPORTING FROM ECNP 2019
Office of Inspector General
Question: Which one of the following statements is incorrect?
A. Office of Inspector General (OIG) is a federal agency of Department of Health & Human Services (HHS) that investigates statutory violations of health care fraud and abuse.
B. The three main legal minefields for physicians are false claims, kickbacks, and self-referrals.
C. Jail terms are part of the penalties provided by law.
D. OIG is also responsible for excluding violators from participating in Medicare/Medicaid programs, as well as curtailing a physician’s license to practice.
E. A private citizen can file a qui tam lawsuit against an errant practitioner or health care entity for fraud and abuse.
Answer: D. Health care fraud, waste, and abuse consume some 10% of federal health expenditures despite well-established laws that attempt to prevent and reduce such losses. The Department of Health & Human Services (HHS) Office of Inspector General, as well as the Department of Justice and the Centers for Medicare & Medicaid Services are charged with enforcing these and other laws like the Emergency Medical Treatment and Labor Act. Their web pages, referenced throughout this article, contain a wealth of information for the practitioner.
The term “Office of Inspector General” (OIG) refers to the oversight division of a federal or state agency charged with identifying and investigating fraud, waste, abuse, and mismanagement within that department or agency. There are currently 73 separate federal offices of inspectors general, which employ armed and unarmed criminal investigators, auditors, forensic auditors called “audigators,” and a variety of other specialists. An Act of Congress in 1976 established the first OIG under HHS. Besides being the first, HHS-OIG is also the largest, with a staff of approximately 1,600. A majority of resources goes toward the oversight of Medicare and Medicaid, as well as programs under other HHS institutions such as the Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration.1
HHS-OIG has the authority to seek civil monetary penalties, assessments, and exclusion against an individual or entity based on a wide variety of prohibited conduct affecting federal health care programs. Stiff penalties are regularly assessed against violators, and jail terms are not uncommon; however, it has no direct jurisdictions over physician licensure or nonfederal programs. The government maintains a pictorial list of its most wanted health care fugitives2 and provides an excellent set of Physician Education Training Materials on its website.3
False Claims Act (FCA)
In the health care arena, violation of FCA (31 U.S.C. §§3729-3733) is the foremost infraction. False claims by physicians can include billing for noncovered services such as experimental treatments, double billing, billing the government as the primary payer, or regularly waiving deductibles and copayments, as well as quality of care issues and unnecessary services. Wrongdoing also includes knowingly using another patient’s name for purposes of, say, federal drug coverage, billing for no-shows, and misrepresenting the diagnosis to justify services, as well as other claims. In the modern doctor’s office, the EMR enables easy check-offs on a preprinted form as documentation of actual work done. However, fraud is implicated if the information is deliberately misleading such as for purposes of upcoding. Importantly, physicians are liable for the actions of their office staff, so it is prudent to oversee and supervise all such activities. Naturally, one should document all claims that are sent and know the rules for allowable and excluded services.
FCA is an old law that was first enacted in 1863. It imposes liability for submitting a payment demand to the federal government where there is actual or constructive knowledge that the claim is false. Intent to defraud is not a required element but knowing or showing reckless disregard of the truth is. However, an error that is negligently committed is insufficient to constitute a violation. Penalties include treble damages, costs and attorney fees, and fines of $11,000 per false claim, as well as possible imprisonment and criminal fines. A so-called whistle-blower may file a lawsuit on behalf of the government and is entitled to a percentage of any recoveries. Whistle-blowers may be current or ex-business partners, hospital or office staff, patients, or competitors. The fact that a claim results from a kickback or is made in violation of the Stark law (discussed below) may also render it fraudulent, thus creating additional liability under FCA.
HHS-OIG, as well as the Department of Justice, discloses named cases of statutory violations on their websites. A few random 2019 examples include a New York licensed doctor was convicted of nine counts in connection with Oxycodone and Fentanyl diversion scheme; a Newton, Mass., geriatrician agreed to pay $680,000 to resolve allegations that he violated the False Claims Act by submitting inflated claims to Medicare and the Massachusetts Medicaid program (MassHealth) for care rendered to nursing home patients; and two Clermont, Fla., ophthalmologists agreed to pay a combined total of $157,312.32 to resolve allegations that they violated FCA by knowingly billing the government for mutually exclusive eyelid repair surgeries.
Anti-Kickback Statute (AKS)
AKS (42 U.S.C. § 1320a-7b[b]) is a criminal law that prohibits the knowing and willful payment of “remuneration” to induce or reward patient referrals or the generation of business involving any item or service payable by federal health care programs. Remuneration includes anything of value and can take many forms besides cash, such as free rent, lavish travel, and excessive compensation for medical directorships or consultancies. Rewarding a referral source may be acceptable in some industries, but is a crime in federal health care programs.
Moreover, the statute covers both the payers of kickbacks (those who offer or pay remuneration) and the recipients of kickbacks. Each party’s intent is a key element of their liability under AKS. Physicians who pay or accept kickbacks face penalties of up to $50,000 per kickback plus three times the amount of the remuneration and criminal prosecution. As an example, a Tulsa, Okla., doctor earlier this year agreed to pay the government $84,666.42 for allegedly accepting illegal kickback payments from a pharmacy, and in another case, a marketer agreed to pay nearly $340,000 for receiving kickbacks in exchange for prescription referrals.
A physician is an attractive target for kickback schemes. The kickback prohibition applies to all sources, even patients. For example, where the Medicare and Medicaid programs require patients to be responsible for copays for services, the health care provider is generally required to collect that money from the patients. Advertising the forgiveness of copayments or routinely waiving these copays would violate AKS. However, one may waive a copayment when a patient cannot afford to pay one or is uninsured. AKS also imposes civil monetary penalties on physicians who offer remuneration to Medicare and Medicaid beneficiaries to influence them to use their services. Note that the government does not need to prove patient harm or financial loss to show that a violation has occurred, and physicians can be guilty even if they rendered services that are medically necessary.
There are so-called safe harbors that protect certain payment and business practices from running afoul of AKS. The rules and requirements are complex, and require full understanding and strict adherence.4
Physician Self-Referral Law
The Physician Self-Referral Law (42 U.S.C. § 1395nn), commonly referred to as the Stark law, prohibits physicians from referring patients to receive “designated health services” payable by Medicare or Medicaid from entities with which the physician or an immediate family member has a financial relationship, unless an exception applies. Financial relationships include both ownership/investment interests and compensation arrangements. A partial list of “designated health services” includes services related to clinical laboratory, physical therapy, radiology, parenteral and enteral supplies, prosthetic devices and supplies, home health care outpatient prescription drugs, and inpatient and outpatient hospital services. This list is not meant to be an exhaustive one.
Stark is a strict liability statute, which means proof of specific intent to violate the law is not required. The law prohibits the submission, or causing the submission, of claims in violation of the law’s restrictions on referrals. Penalties for physicians who violate the Stark law include fines, as well as exclusion from participation in federal health care programs. Like AKS, Stark law features its own safe harbors.
Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some materials may have been discussed in earlier columns. For additional information, readers may contact the author at [email protected].
References
1. HHS Office of Inspector General. About OIG. https://oig.hhs.gov/about-oig/about-us/index.asp
2. HHS Office of Inspector General. OIG most wanted fugitives.
3. HHS Office of Inspector General. “Physician education training materials.” A roadmap for new physicians: Avoiding Medicare and Medicaid fraud and abuse.
4. HHS Office of Inspector General. Safe harbor regulations.
Question: Which one of the following statements is incorrect?
A. Office of Inspector General (OIG) is a federal agency of Department of Health & Human Services (HHS) that investigates statutory violations of health care fraud and abuse.
B. The three main legal minefields for physicians are false claims, kickbacks, and self-referrals.
C. Jail terms are part of the penalties provided by law.
D. OIG is also responsible for excluding violators from participating in Medicare/Medicaid programs, as well as curtailing a physician’s license to practice.
E. A private citizen can file a qui tam lawsuit against an errant practitioner or health care entity for fraud and abuse.
Answer: D. Health care fraud, waste, and abuse consume some 10% of federal health expenditures despite well-established laws that attempt to prevent and reduce such losses. The Department of Health & Human Services (HHS) Office of Inspector General, as well as the Department of Justice and the Centers for Medicare & Medicaid Services are charged with enforcing these and other laws like the Emergency Medical Treatment and Labor Act. Their web pages, referenced throughout this article, contain a wealth of information for the practitioner.
The term “Office of Inspector General” (OIG) refers to the oversight division of a federal or state agency charged with identifying and investigating fraud, waste, abuse, and mismanagement within that department or agency. There are currently 73 separate federal offices of inspectors general, which employ armed and unarmed criminal investigators, auditors, forensic auditors called “audigators,” and a variety of other specialists. An Act of Congress in 1976 established the first OIG under HHS. Besides being the first, HHS-OIG is also the largest, with a staff of approximately 1,600. A majority of resources goes toward the oversight of Medicare and Medicaid, as well as programs under other HHS institutions such as the Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration.1
HHS-OIG has the authority to seek civil monetary penalties, assessments, and exclusion against an individual or entity based on a wide variety of prohibited conduct affecting federal health care programs. Stiff penalties are regularly assessed against violators, and jail terms are not uncommon; however, it has no direct jurisdictions over physician licensure or nonfederal programs. The government maintains a pictorial list of its most wanted health care fugitives2 and provides an excellent set of Physician Education Training Materials on its website.3
False Claims Act (FCA)
In the health care arena, violation of FCA (31 U.S.C. §§3729-3733) is the foremost infraction. False claims by physicians can include billing for noncovered services such as experimental treatments, double billing, billing the government as the primary payer, or regularly waiving deductibles and copayments, as well as quality of care issues and unnecessary services. Wrongdoing also includes knowingly using another patient’s name for purposes of, say, federal drug coverage, billing for no-shows, and misrepresenting the diagnosis to justify services, as well as other claims. In the modern doctor’s office, the EMR enables easy check-offs on a preprinted form as documentation of actual work done. However, fraud is implicated if the information is deliberately misleading such as for purposes of upcoding. Importantly, physicians are liable for the actions of their office staff, so it is prudent to oversee and supervise all such activities. Naturally, one should document all claims that are sent and know the rules for allowable and excluded services.
FCA is an old law that was first enacted in 1863. It imposes liability for submitting a payment demand to the federal government where there is actual or constructive knowledge that the claim is false. Intent to defraud is not a required element but knowing or showing reckless disregard of the truth is. However, an error that is negligently committed is insufficient to constitute a violation. Penalties include treble damages, costs and attorney fees, and fines of $11,000 per false claim, as well as possible imprisonment and criminal fines. A so-called whistle-blower may file a lawsuit on behalf of the government and is entitled to a percentage of any recoveries. Whistle-blowers may be current or ex-business partners, hospital or office staff, patients, or competitors. The fact that a claim results from a kickback or is made in violation of the Stark law (discussed below) may also render it fraudulent, thus creating additional liability under FCA.
HHS-OIG, as well as the Department of Justice, discloses named cases of statutory violations on their websites. A few random 2019 examples include a New York licensed doctor was convicted of nine counts in connection with Oxycodone and Fentanyl diversion scheme; a Newton, Mass., geriatrician agreed to pay $680,000 to resolve allegations that he violated the False Claims Act by submitting inflated claims to Medicare and the Massachusetts Medicaid program (MassHealth) for care rendered to nursing home patients; and two Clermont, Fla., ophthalmologists agreed to pay a combined total of $157,312.32 to resolve allegations that they violated FCA by knowingly billing the government for mutually exclusive eyelid repair surgeries.
Anti-Kickback Statute (AKS)
AKS (42 U.S.C. § 1320a-7b[b]) is a criminal law that prohibits the knowing and willful payment of “remuneration” to induce or reward patient referrals or the generation of business involving any item or service payable by federal health care programs. Remuneration includes anything of value and can take many forms besides cash, such as free rent, lavish travel, and excessive compensation for medical directorships or consultancies. Rewarding a referral source may be acceptable in some industries, but is a crime in federal health care programs.
Moreover, the statute covers both the payers of kickbacks (those who offer or pay remuneration) and the recipients of kickbacks. Each party’s intent is a key element of their liability under AKS. Physicians who pay or accept kickbacks face penalties of up to $50,000 per kickback plus three times the amount of the remuneration and criminal prosecution. As an example, a Tulsa, Okla., doctor earlier this year agreed to pay the government $84,666.42 for allegedly accepting illegal kickback payments from a pharmacy, and in another case, a marketer agreed to pay nearly $340,000 for receiving kickbacks in exchange for prescription referrals.
A physician is an attractive target for kickback schemes. The kickback prohibition applies to all sources, even patients. For example, where the Medicare and Medicaid programs require patients to be responsible for copays for services, the health care provider is generally required to collect that money from the patients. Advertising the forgiveness of copayments or routinely waiving these copays would violate AKS. However, one may waive a copayment when a patient cannot afford to pay one or is uninsured. AKS also imposes civil monetary penalties on physicians who offer remuneration to Medicare and Medicaid beneficiaries to influence them to use their services. Note that the government does not need to prove patient harm or financial loss to show that a violation has occurred, and physicians can be guilty even if they rendered services that are medically necessary.
There are so-called safe harbors that protect certain payment and business practices from running afoul of AKS. The rules and requirements are complex, and require full understanding and strict adherence.4
Physician Self-Referral Law
The Physician Self-Referral Law (42 U.S.C. § 1395nn), commonly referred to as the Stark law, prohibits physicians from referring patients to receive “designated health services” payable by Medicare or Medicaid from entities with which the physician or an immediate family member has a financial relationship, unless an exception applies. Financial relationships include both ownership/investment interests and compensation arrangements. A partial list of “designated health services” includes services related to clinical laboratory, physical therapy, radiology, parenteral and enteral supplies, prosthetic devices and supplies, home health care outpatient prescription drugs, and inpatient and outpatient hospital services. This list is not meant to be an exhaustive one.
Stark is a strict liability statute, which means proof of specific intent to violate the law is not required. The law prohibits the submission, or causing the submission, of claims in violation of the law’s restrictions on referrals. Penalties for physicians who violate the Stark law include fines, as well as exclusion from participation in federal health care programs. Like AKS, Stark law features its own safe harbors.
Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some materials may have been discussed in earlier columns. For additional information, readers may contact the author at [email protected].
References
1. HHS Office of Inspector General. About OIG. https://oig.hhs.gov/about-oig/about-us/index.asp
2. HHS Office of Inspector General. OIG most wanted fugitives.
3. HHS Office of Inspector General. “Physician education training materials.” A roadmap for new physicians: Avoiding Medicare and Medicaid fraud and abuse.
4. HHS Office of Inspector General. Safe harbor regulations.
Question: Which one of the following statements is incorrect?
A. Office of Inspector General (OIG) is a federal agency of Department of Health & Human Services (HHS) that investigates statutory violations of health care fraud and abuse.
B. The three main legal minefields for physicians are false claims, kickbacks, and self-referrals.
C. Jail terms are part of the penalties provided by law.
D. OIG is also responsible for excluding violators from participating in Medicare/Medicaid programs, as well as curtailing a physician’s license to practice.
E. A private citizen can file a qui tam lawsuit against an errant practitioner or health care entity for fraud and abuse.
Answer: D. Health care fraud, waste, and abuse consume some 10% of federal health expenditures despite well-established laws that attempt to prevent and reduce such losses. The Department of Health & Human Services (HHS) Office of Inspector General, as well as the Department of Justice and the Centers for Medicare & Medicaid Services are charged with enforcing these and other laws like the Emergency Medical Treatment and Labor Act. Their web pages, referenced throughout this article, contain a wealth of information for the practitioner.
The term “Office of Inspector General” (OIG) refers to the oversight division of a federal or state agency charged with identifying and investigating fraud, waste, abuse, and mismanagement within that department or agency. There are currently 73 separate federal offices of inspectors general, which employ armed and unarmed criminal investigators, auditors, forensic auditors called “audigators,” and a variety of other specialists. An Act of Congress in 1976 established the first OIG under HHS. Besides being the first, HHS-OIG is also the largest, with a staff of approximately 1,600. A majority of resources goes toward the oversight of Medicare and Medicaid, as well as programs under other HHS institutions such as the Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration.1
HHS-OIG has the authority to seek civil monetary penalties, assessments, and exclusion against an individual or entity based on a wide variety of prohibited conduct affecting federal health care programs. Stiff penalties are regularly assessed against violators, and jail terms are not uncommon; however, it has no direct jurisdictions over physician licensure or nonfederal programs. The government maintains a pictorial list of its most wanted health care fugitives2 and provides an excellent set of Physician Education Training Materials on its website.3
False Claims Act (FCA)
In the health care arena, violation of FCA (31 U.S.C. §§3729-3733) is the foremost infraction. False claims by physicians can include billing for noncovered services such as experimental treatments, double billing, billing the government as the primary payer, or regularly waiving deductibles and copayments, as well as quality of care issues and unnecessary services. Wrongdoing also includes knowingly using another patient’s name for purposes of, say, federal drug coverage, billing for no-shows, and misrepresenting the diagnosis to justify services, as well as other claims. In the modern doctor’s office, the EMR enables easy check-offs on a preprinted form as documentation of actual work done. However, fraud is implicated if the information is deliberately misleading such as for purposes of upcoding. Importantly, physicians are liable for the actions of their office staff, so it is prudent to oversee and supervise all such activities. Naturally, one should document all claims that are sent and know the rules for allowable and excluded services.
FCA is an old law that was first enacted in 1863. It imposes liability for submitting a payment demand to the federal government where there is actual or constructive knowledge that the claim is false. Intent to defraud is not a required element but knowing or showing reckless disregard of the truth is. However, an error that is negligently committed is insufficient to constitute a violation. Penalties include treble damages, costs and attorney fees, and fines of $11,000 per false claim, as well as possible imprisonment and criminal fines. A so-called whistle-blower may file a lawsuit on behalf of the government and is entitled to a percentage of any recoveries. Whistle-blowers may be current or ex-business partners, hospital or office staff, patients, or competitors. The fact that a claim results from a kickback or is made in violation of the Stark law (discussed below) may also render it fraudulent, thus creating additional liability under FCA.
HHS-OIG, as well as the Department of Justice, discloses named cases of statutory violations on their websites. A few random 2019 examples include a New York licensed doctor was convicted of nine counts in connection with Oxycodone and Fentanyl diversion scheme; a Newton, Mass., geriatrician agreed to pay $680,000 to resolve allegations that he violated the False Claims Act by submitting inflated claims to Medicare and the Massachusetts Medicaid program (MassHealth) for care rendered to nursing home patients; and two Clermont, Fla., ophthalmologists agreed to pay a combined total of $157,312.32 to resolve allegations that they violated FCA by knowingly billing the government for mutually exclusive eyelid repair surgeries.
Anti-Kickback Statute (AKS)
AKS (42 U.S.C. § 1320a-7b[b]) is a criminal law that prohibits the knowing and willful payment of “remuneration” to induce or reward patient referrals or the generation of business involving any item or service payable by federal health care programs. Remuneration includes anything of value and can take many forms besides cash, such as free rent, lavish travel, and excessive compensation for medical directorships or consultancies. Rewarding a referral source may be acceptable in some industries, but is a crime in federal health care programs.
Moreover, the statute covers both the payers of kickbacks (those who offer or pay remuneration) and the recipients of kickbacks. Each party’s intent is a key element of their liability under AKS. Physicians who pay or accept kickbacks face penalties of up to $50,000 per kickback plus three times the amount of the remuneration and criminal prosecution. As an example, a Tulsa, Okla., doctor earlier this year agreed to pay the government $84,666.42 for allegedly accepting illegal kickback payments from a pharmacy, and in another case, a marketer agreed to pay nearly $340,000 for receiving kickbacks in exchange for prescription referrals.
A physician is an attractive target for kickback schemes. The kickback prohibition applies to all sources, even patients. For example, where the Medicare and Medicaid programs require patients to be responsible for copays for services, the health care provider is generally required to collect that money from the patients. Advertising the forgiveness of copayments or routinely waiving these copays would violate AKS. However, one may waive a copayment when a patient cannot afford to pay one or is uninsured. AKS also imposes civil monetary penalties on physicians who offer remuneration to Medicare and Medicaid beneficiaries to influence them to use their services. Note that the government does not need to prove patient harm or financial loss to show that a violation has occurred, and physicians can be guilty even if they rendered services that are medically necessary.
There are so-called safe harbors that protect certain payment and business practices from running afoul of AKS. The rules and requirements are complex, and require full understanding and strict adherence.4
Physician Self-Referral Law
The Physician Self-Referral Law (42 U.S.C. § 1395nn), commonly referred to as the Stark law, prohibits physicians from referring patients to receive “designated health services” payable by Medicare or Medicaid from entities with which the physician or an immediate family member has a financial relationship, unless an exception applies. Financial relationships include both ownership/investment interests and compensation arrangements. A partial list of “designated health services” includes services related to clinical laboratory, physical therapy, radiology, parenteral and enteral supplies, prosthetic devices and supplies, home health care outpatient prescription drugs, and inpatient and outpatient hospital services. This list is not meant to be an exhaustive one.
Stark is a strict liability statute, which means proof of specific intent to violate the law is not required. The law prohibits the submission, or causing the submission, of claims in violation of the law’s restrictions on referrals. Penalties for physicians who violate the Stark law include fines, as well as exclusion from participation in federal health care programs. Like AKS, Stark law features its own safe harbors.
Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some materials may have been discussed in earlier columns. For additional information, readers may contact the author at [email protected].
References
1. HHS Office of Inspector General. About OIG. https://oig.hhs.gov/about-oig/about-us/index.asp
2. HHS Office of Inspector General. OIG most wanted fugitives.
3. HHS Office of Inspector General. “Physician education training materials.” A roadmap for new physicians: Avoiding Medicare and Medicaid fraud and abuse.
4. HHS Office of Inspector General. Safe harbor regulations.