The human papillomavirus (HPV) vaccination is not associated with the development of multiple sclerosis (MS) or other demyelinating diseases, according to a study published January 6 in JAMA. Researchers examined Danish and Swedish girls and women between ages 10 and 44. Participants were followed up from 2006 to 2013. A total of 3,983,824 girls and women were eligible for inclusion in this study. Of these individuals, 789,082 were vaccinated, and 1,927,581 HPV vaccine doses were administered. At follow-up, 4,322 cases of MS and 3,300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period of two years following vaccination. “These findings do not support concerns about a causal relationship between HPV vaccination and demyelinating diseases,” the researchers stated.

No evidence of disease activity (NEDA) is a difficult outcome for patients with multiple sclerosis (MS) to sustain in the long term, even with treatment, according to a study published online ahead of print December 22 in JAMA Neurology. Researchers investigated the sustainability of NEDA over seven years in a group of 219 patients with MS. Patients had seven years of follow-up that included yearly brain MRI and biannual clinic visits. Investigators found that of 215 patients, 99 (46%) had NEDA for clinical and MRI measures at one year. At two years, 60 of 218 patients (27.5%) maintained NEDA, and 17 of 216 patients (7.9%) sustained NEDA after seven years. There was no difference in NEDA status for patients with early MS, compared with patients with more established disease.

Pharnext announced the proof of concept of its pleotherapy research and development approach based on a proprietary network pharmacology platform that identifies synergistic combinations of drugs already approved for other diseases. According to two reports published online December 10, 2014, in the Orphanet Journal of Rare Diseases, Pharnext’s lead pleodrug, PXT-3003, has shown positive results in preclinical and phase 2 clinical studies. The first paper shows consistent and synergistic preclinical data for PXT-3003 in two Charcot–Marie–Tooth disease type 1A (CMT 1A) rodent models. The second paper presents positive phase 2 results of PXT-3003 in 80 patients with mild to moderate CMT 1A.

Patients with acute ischemic stroke admitted to tertiary stroke centers during July had similar outcomes to patients admitted during other months, despite receiving slightly less frequent thrombolysis and stroke unit care, according to a study published online ahead of print December 19 in the Journal of Stroke and Cerebrovascular Diseases. Researchers examined 10,319 patients with acute ischemic stroke between July 1, 2003 and March 31, 2008. The research team evaluated referrals to long-term care facilities, length of hospital stay, hospital readmissions or emergency department visits within 30 days of hospital discharge, and hospital readmissions within 30 days from discharge due to stroke. “Ischemic stroke patients admitted in July were less likely to receive clot-busting drugs or be admitted to stroke units, but ultimately patients did just as well regardless of the month,” stated the investigators.

Insomnia symptoms are an important factor for explaining the mechanism by which alcohol use increases suicide risk, according to a study published December 15 in the Journal of Clinical Sleep Medicine. The study included 375 undergraduate students at a large, public university in the southeastern United States. Participants completed an online questionnaire that examined insomnia symptoms, nightmares, alcohol use, and suicide risk. Alcohol use was significantly associated with suicide risk among women. In addition, further analysis revealed that insomnia symptoms explained a significant proportion of the relationship between alcohol and suicide risk. Investigators found no direct effect of alcohol use on suicide risk in men, but they observed a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms.

The virtual supermarket (VSM) application correctly identifies 87.30% of patients with mild cognitive impairment (MCI), a level of diagnostic accuracy similar to that of standardized neuropsychologic tests, according to a study published online ahead of print November 25 in the Journal of Alzheimer’s Disease. Two groups, one of healthy older adults and one of patients with MCI, were recruited from day centers for people with cognitive disorders. Participants used the VSM application and underwent a battery of neuropsychologic tests. The VSM application accurately distinguished between patients with MCI and healthy older adults, but it was unable to differentiate between MCI subtypes. Overall, the VSM application is a valid method of screening for MCI in an older adult population, but it cannot be used for MCI subtype assessment.

—Kimberly D. Williams

The human papillomavirus (HPV) vaccination is not associated with the development of multiple sclerosis (MS) or other demyelinating diseases, according to a study published January 6 in JAMA. Researchers examined Danish and Swedish girls and women between ages 10 and 44. Participants were followed up from 2006 to 2013. A total of 3,983,824 girls and women were eligible for inclusion in this study. Of these individuals, 789,082 were vaccinated, and 1,927,581 HPV vaccine doses were administered. At follow-up, 4,322 cases of MS and 3,300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period of two years following vaccination. “These findings do not support concerns about a causal relationship between HPV vaccination and demyelinating diseases,” the researchers stated.

No evidence of disease activity (NEDA) is a difficult outcome for patients with multiple sclerosis (MS) to sustain in the long term, even with treatment, according to a study published online ahead of print December 22 in JAMA Neurology. Researchers investigated the sustainability of NEDA over seven years in a group of 219 patients with MS. Patients had seven years of follow-up that included yearly brain MRI and biannual clinic visits. Investigators found that of 215 patients, 99 (46%) had NEDA for clinical and MRI measures at one year. At two years, 60 of 218 patients (27.5%) maintained NEDA, and 17 of 216 patients (7.9%) sustained NEDA after seven years. There was no difference in NEDA status for patients with early MS, compared with patients with more established disease.

Pharnext announced the proof of concept of its pleotherapy research and development approach based on a proprietary network pharmacology platform that identifies synergistic combinations of drugs already approved for other diseases. According to two reports published online December 10, 2014, in the Orphanet Journal of Rare Diseases, Pharnext’s lead pleodrug, PXT-3003, has shown positive results in preclinical and phase 2 clinical studies. The first paper shows consistent and synergistic preclinical data for PXT-3003 in two Charcot–Marie–Tooth disease type 1A (CMT 1A) rodent models. The second paper presents positive phase 2 results of PXT-3003 in 80 patients with mild to moderate CMT 1A.

Patients with acute ischemic stroke admitted to tertiary stroke centers during July had similar outcomes to patients admitted during other months, despite receiving slightly less frequent thrombolysis and stroke unit care, according to a study published online ahead of print December 19 in the Journal of Stroke and Cerebrovascular Diseases. Researchers examined 10,319 patients with acute ischemic stroke between July 1, 2003 and March 31, 2008. The research team evaluated referrals to long-term care facilities, length of hospital stay, hospital readmissions or emergency department visits within 30 days of hospital discharge, and hospital readmissions within 30 days from discharge due to stroke. “Ischemic stroke patients admitted in July were less likely to receive clot-busting drugs or be admitted to stroke units, but ultimately patients did just as well regardless of the month,” stated the investigators.

Insomnia symptoms are an important factor for explaining the mechanism by which alcohol use increases suicide risk, according to a study published December 15 in the Journal of Clinical Sleep Medicine. The study included 375 undergraduate students at a large, public university in the southeastern United States. Participants completed an online questionnaire that examined insomnia symptoms, nightmares, alcohol use, and suicide risk. Alcohol use was significantly associated with suicide risk among women. In addition, further analysis revealed that insomnia symptoms explained a significant proportion of the relationship between alcohol and suicide risk. Investigators found no direct effect of alcohol use on suicide risk in men, but they observed a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms.

The virtual supermarket (VSM) application correctly identifies 87.30% of patients with mild cognitive impairment (MCI), a level of diagnostic accuracy similar to that of standardized neuropsychologic tests, according to a study published online ahead of print November 25 in the Journal of Alzheimer’s Disease. Two groups, one of healthy older adults and one of patients with MCI, were recruited from day centers for people with cognitive disorders. Participants used the VSM application and underwent a battery of neuropsychologic tests. The VSM application accurately distinguished between patients with MCI and healthy older adults, but it was unable to differentiate between MCI subtypes. Overall, the VSM application is a valid method of screening for MCI in an older adult population, but it cannot be used for MCI subtype assessment.

—Kimberly D. Williams

The human papillomavirus (HPV) vaccination is not associated with the development of multiple sclerosis (MS) or other demyelinating diseases, according to a study published January 6 in JAMA. Researchers examined Danish and Swedish girls and women between ages 10 and 44. Participants were followed up from 2006 to 2013. A total of 3,983,824 girls and women were eligible for inclusion in this study. Of these individuals, 789,082 were vaccinated, and 1,927,581 HPV vaccine doses were administered. At follow-up, 4,322 cases of MS and 3,300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period of two years following vaccination. “These findings do not support concerns about a causal relationship between HPV vaccination and demyelinating diseases,” the researchers stated.

No evidence of disease activity (NEDA) is a difficult outcome for patients with multiple sclerosis (MS) to sustain in the long term, even with treatment, according to a study published online ahead of print December 22 in JAMA Neurology. Researchers investigated the sustainability of NEDA over seven years in a group of 219 patients with MS. Patients had seven years of follow-up that included yearly brain MRI and biannual clinic visits. Investigators found that of 215 patients, 99 (46%) had NEDA for clinical and MRI measures at one year. At two years, 60 of 218 patients (27.5%) maintained NEDA, and 17 of 216 patients (7.9%) sustained NEDA after seven years. There was no difference in NEDA status for patients with early MS, compared with patients with more established disease.

Pharnext announced the proof of concept of its pleotherapy research and development approach based on a proprietary network pharmacology platform that identifies synergistic combinations of drugs already approved for other diseases. According to two reports published online December 10, 2014, in the Orphanet Journal of Rare Diseases, Pharnext’s lead pleodrug, PXT-3003, has shown positive results in preclinical and phase 2 clinical studies. The first paper shows consistent and synergistic preclinical data for PXT-3003 in two Charcot–Marie–Tooth disease type 1A (CMT 1A) rodent models. The second paper presents positive phase 2 results of PXT-3003 in 80 patients with mild to moderate CMT 1A.

Patients with acute ischemic stroke admitted to tertiary stroke centers during July had similar outcomes to patients admitted during other months, despite receiving slightly less frequent thrombolysis and stroke unit care, according to a study published online ahead of print December 19 in the Journal of Stroke and Cerebrovascular Diseases. Researchers examined 10,319 patients with acute ischemic stroke between July 1, 2003 and March 31, 2008. The research team evaluated referrals to long-term care facilities, length of hospital stay, hospital readmissions or emergency department visits within 30 days of hospital discharge, and hospital readmissions within 30 days from discharge due to stroke. “Ischemic stroke patients admitted in July were less likely to receive clot-busting drugs or be admitted to stroke units, but ultimately patients did just as well regardless of the month,” stated the investigators.

Insomnia symptoms are an important factor for explaining the mechanism by which alcohol use increases suicide risk, according to a study published December 15 in the Journal of Clinical Sleep Medicine. The study included 375 undergraduate students at a large, public university in the southeastern United States. Participants completed an online questionnaire that examined insomnia symptoms, nightmares, alcohol use, and suicide risk. Alcohol use was significantly associated with suicide risk among women. In addition, further analysis revealed that insomnia symptoms explained a significant proportion of the relationship between alcohol and suicide risk. Investigators found no direct effect of alcohol use on suicide risk in men, but they observed a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms.

The virtual supermarket (VSM) application correctly identifies 87.30% of patients with mild cognitive impairment (MCI), a level of diagnostic accuracy similar to that of standardized neuropsychologic tests, according to a study published online ahead of print November 25 in the Journal of Alzheimer’s Disease. Two groups, one of healthy older adults and one of patients with MCI, were recruited from day centers for people with cognitive disorders. Participants used the VSM application and underwent a battery of neuropsychologic tests. The VSM application accurately distinguished between patients with MCI and healthy older adults, but it was unable to differentiate between MCI subtypes. Overall, the VSM application is a valid method of screening for MCI in an older adult population, but it cannot be used for MCI subtype assessment.

—Kimberly D. Williams

SCOTTSDALE, Ariz.– “It’s surprising to me today, when I go proctor or watch a case, how people don’t understand the impact of radiation,” Dr. Mark A. Farber, professor of surgery and radiology at the University of North Carolina, Chapel Hill, said at the Southern Association for Vascular Surgery annual meeting. “Many times, I see people’s hands underneath the machine and on the fluoroscopy image.”

This flouting of the so-called ALARA (as low as reasonably achievable) principle happens in part because the number of complex procedures performed by vascular surgeons is increasing, despite what presenter Dr. Melissa Kirkwood, a vascular surgeon at the University of Texas Southwestern Medical Center, Dallas, told the audience is a lack of training in radiation dose terminology and basic safety principles. Yet, practicing excellent radiation safety protocols is “paramount” according to Dr. Farber who, along with Dr. Kirkwood, shared insights on how to minimize dose to both patients and vascular specialists, whether it be from primary, leakage, or scatter radiation.

Table up, detector down

Minimizing the air gap by as little as 100 mm – from 700 mm to 600 mm, for example – can reduce the dose of radiation from 17%-29%, whereas a 
10-cm increase in the air gap can result in as much as a 20%-38% increase in the radiation skin dose. This is essentially the application of the inverse square law, according to Dr. Kirkwood.

Dr. Farber said that some of the newer, more advanced machines have sensors that automatically detect where the collector should be in relation to the patient, but if your machine doesn’t have these “bells and whistles … remember that the skin dose decreases as the air gap decreases.”

Another advantage to using new imaging systems, according to Dr. Farber, is that they allow the use of pulsed fluoroscopy for as few as 2 or 3 pulses/sec. The selected pulse rate determines the number of fluoroscopic image frames that are generated by the machine per second. This is significant when the dose savings are essential and when performing simpler procedures, he said. “If you go from 7.5 frames down to 3 frames/sec, you can decrease the exposure for both you and your patient.”

Use between 15 and 30 pulses/sec for critical procedures where precision is crucial, but reducing the rate to 7.5 pulses/sec may result in as much as 70% less of a skin dose.

Add radiation barriers

Don’t assume that the lead shielding is doing the job. “It’s important that you keep up on this and have it tested regularly,” said Dr. Farber, who recently discovered his thyroid shield was cracked and needed to be replaced. Also, consider the lead shielding of your staff, which, even if it is not used as frequently as the physician’s, can suffer from improper handling. “They fold it or crinkle it up and drop it on the floor. This can lead to problems,” he said. And be sure to remember leaded glasses, lead drapes for the sides of the table, and leaded ceiling-mounted or standing shields.

For extra protection, Dr. Farber recommended the use of disposable protective drapes with cut-outs that allow access to the patient while helping to reduce the amount of scatter radiation exposure to the operator’s limbs. At a tally of anywhere from 1 to 10 mGy/hour, scatter radiation emanating from the patient is a particular risk to the operator’s legs from the knees down, said Dr. Kirkwood, “depending on how tall you are.”

Using the disposable drapes also can result in a 12-fold decrease in the amount of scatter on the eyes, a 25-fold decrease in thyroid exposure to scatter, and a 29-fold decrease in the hands being exposed. “They can be cumbersome at times, I admit,” Dr. Farber said. “But there is no substitute for using protective drapes.”

Leaded aprons also help cut radiation transmission rates, even if they are not foolproof. Wearing two-piece leaded apron systems can help cut down the body strain from the weight of the aprons; however, Dr. Farber said that, at his institution, they use a suspended body shield system operated by a boom so there is no physical stress on the clinician. Because the weightless system also provides additional protection for the specialist’s head and limbs, Dr. Farber said that the hefty price tag is justified. “The way I sold it to the hospital was I told them I could stop doing procedures, or they could get me one of these systems so I could do more procedures,” he said, adding he is having a weightless system installed on each side of the table. “They’ll get their money’s worth by the fact that you’re not over your exposure limit.”

And finally, don’t forget to protect the anesthesiologist! A standing shield that gives broad coverage area should suffice, Dr. Farber said.

Alter the intensifier position

Altering the angle can help ensure that one area of the patient’s body isn’t being overexposed to radiation. Since previously irradiated skin reacts abnormally when re-exposed to radiation because the regeneration and repair of the dermis can take up to several weeks after the initial insult, the timing of the intervals between exposures is critical, said Dr. Kirkwood, adding that the Joint Commission recommended that all doses of fluoroscopically guided interventions performed within the past 6-12 months should be considered when assessing potential skin injury risk.

Use collimation

Making it tighter, for example, can help improve image quality and reduce the radiation dose to both the patient and the operator, as can varying the acquisition rates.

Exit the room during DSA

During digital subtraction angiography, Dr. Farber said to “get away from the table if you can! It’s a huge dose you don’t need to be exposed to if you don’t need to be right next to the machine.” Dr. Kirkwood agreed: “Angiography is 10-100 times more dose than fluoroscopy.”

Reduce magnification

Using a larger monitor allows the operator to see more detail without increasing the magnification, which also increases the dose in the amount of the diameter over the diameter squared. “By not magnifying up [from a field of view of 14 to 28], you will save yourself a factor of at least 4,” Dr. Farber said. “And the actual dose may be even less.”

Optimize imaging

Today’s advanced imaging systems make it easy to produce many high-quality images – CT scans and ultrasounds – that allow a more comprehensive picture. Having various image sources on screen at once is “practice changing” because it can help clinicians see more possibilities for “how to do the case,” said Dr. Farber. “I’ve never heard anyone say, ’Well, I wish I didn’t have that extra imaging next to me.’ ”

Save images

But once you get it, don’t forget to keep it. “Many times you do an acquisition, you move the machine, and you realize you forget to save the image and now you’ve got to go back and do it all over again,” Dr. Farber lamented. But by once again making technology your friend, with functions that allow auto-return to previous positions, among other auto-commands, you can save the needed information and reduce any unnecessary dose exposure for both yourself and the patient, he said.

Protect your eyes

Cataracts are still all too common in the field, according to Dr. Farber. “It’s important that you have side shields on your glasses to cut down on the amount of radiation that comes in and around the glasses.” Eschew glasses that don’t overtly hug your face.

Geometric differences

Don’t forget that, if you’re standing on the side of the imaging source, the scattering effect will be greater than if you’re on the side of the image receptor. Once again, an understanding of the inverse square law can be protective, according to Dr. Kirkwood: “As x-rays exit the source, there is an exponential decrease in the number of x-rays per unit area as the distance from the source increases.”

“It’s simple stuff,” concluded Dr. Farber. “If you get in the habit of doing these things you will cut down your radiation exposure.”

Neither Dr. Farber nor Dr. Kirkwood had any relevant disclosures.

[email protected]
On Twitter @whitneymcknight

SCOTTSDALE, Ariz.– “It’s surprising to me today, when I go proctor or watch a case, how people don’t understand the impact of radiation,” Dr. Mark A. Farber, professor of surgery and radiology at the University of North Carolina, Chapel Hill, said at the Southern Association for Vascular Surgery annual meeting. “Many times, I see people’s hands underneath the machine and on the fluoroscopy image.”

This flouting of the so-called ALARA (as low as reasonably achievable) principle happens in part because the number of complex procedures performed by vascular surgeons is increasing, despite what presenter Dr. Melissa Kirkwood, a vascular surgeon at the University of Texas Southwestern Medical Center, Dallas, told the audience is a lack of training in radiation dose terminology and basic safety principles. Yet, practicing excellent radiation safety protocols is “paramount” according to Dr. Farber who, along with Dr. Kirkwood, shared insights on how to minimize dose to both patients and vascular specialists, whether it be from primary, leakage, or scatter radiation.

Table up, detector down

Minimizing the air gap by as little as 100 mm – from 700 mm to 600 mm, for example – can reduce the dose of radiation from 17%-29%, whereas a 
10-cm increase in the air gap can result in as much as a 20%-38% increase in the radiation skin dose. This is essentially the application of the inverse square law, according to Dr. Kirkwood.

Dr. Farber said that some of the newer, more advanced machines have sensors that automatically detect where the collector should be in relation to the patient, but if your machine doesn’t have these “bells and whistles … remember that the skin dose decreases as the air gap decreases.”

Another advantage to using new imaging systems, according to Dr. Farber, is that they allow the use of pulsed fluoroscopy for as few as 2 or 3 pulses/sec. The selected pulse rate determines the number of fluoroscopic image frames that are generated by the machine per second. This is significant when the dose savings are essential and when performing simpler procedures, he said. “If you go from 7.5 frames down to 3 frames/sec, you can decrease the exposure for both you and your patient.”

Use between 15 and 30 pulses/sec for critical procedures where precision is crucial, but reducing the rate to 7.5 pulses/sec may result in as much as 70% less of a skin dose.

Add radiation barriers

Don’t assume that the lead shielding is doing the job. “It’s important that you keep up on this and have it tested regularly,” said Dr. Farber, who recently discovered his thyroid shield was cracked and needed to be replaced. Also, consider the lead shielding of your staff, which, even if it is not used as frequently as the physician’s, can suffer from improper handling. “They fold it or crinkle it up and drop it on the floor. This can lead to problems,” he said. And be sure to remember leaded glasses, lead drapes for the sides of the table, and leaded ceiling-mounted or standing shields.

For extra protection, Dr. Farber recommended the use of disposable protective drapes with cut-outs that allow access to the patient while helping to reduce the amount of scatter radiation exposure to the operator’s limbs. At a tally of anywhere from 1 to 10 mGy/hour, scatter radiation emanating from the patient is a particular risk to the operator’s legs from the knees down, said Dr. Kirkwood, “depending on how tall you are.”

Using the disposable drapes also can result in a 12-fold decrease in the amount of scatter on the eyes, a 25-fold decrease in thyroid exposure to scatter, and a 29-fold decrease in the hands being exposed. “They can be cumbersome at times, I admit,” Dr. Farber said. “But there is no substitute for using protective drapes.”

Leaded aprons also help cut radiation transmission rates, even if they are not foolproof. Wearing two-piece leaded apron systems can help cut down the body strain from the weight of the aprons; however, Dr. Farber said that, at his institution, they use a suspended body shield system operated by a boom so there is no physical stress on the clinician. Because the weightless system also provides additional protection for the specialist’s head and limbs, Dr. Farber said that the hefty price tag is justified. “The way I sold it to the hospital was I told them I could stop doing procedures, or they could get me one of these systems so I could do more procedures,” he said, adding he is having a weightless system installed on each side of the table. “They’ll get their money’s worth by the fact that you’re not over your exposure limit.”

And finally, don’t forget to protect the anesthesiologist! A standing shield that gives broad coverage area should suffice, Dr. Farber said.

Alter the intensifier position

Altering the angle can help ensure that one area of the patient’s body isn’t being overexposed to radiation. Since previously irradiated skin reacts abnormally when re-exposed to radiation because the regeneration and repair of the dermis can take up to several weeks after the initial insult, the timing of the intervals between exposures is critical, said Dr. Kirkwood, adding that the Joint Commission recommended that all doses of fluoroscopically guided interventions performed within the past 6-12 months should be considered when assessing potential skin injury risk.

Use collimation

Making it tighter, for example, can help improve image quality and reduce the radiation dose to both the patient and the operator, as can varying the acquisition rates.

Exit the room during DSA

During digital subtraction angiography, Dr. Farber said to “get away from the table if you can! It’s a huge dose you don’t need to be exposed to if you don’t need to be right next to the machine.” Dr. Kirkwood agreed: “Angiography is 10-100 times more dose than fluoroscopy.”

Reduce magnification

Using a larger monitor allows the operator to see more detail without increasing the magnification, which also increases the dose in the amount of the diameter over the diameter squared. “By not magnifying up [from a field of view of 14 to 28], you will save yourself a factor of at least 4,” Dr. Farber said. “And the actual dose may be even less.”

Optimize imaging

Today’s advanced imaging systems make it easy to produce many high-quality images – CT scans and ultrasounds – that allow a more comprehensive picture. Having various image sources on screen at once is “practice changing” because it can help clinicians see more possibilities for “how to do the case,” said Dr. Farber. “I’ve never heard anyone say, ’Well, I wish I didn’t have that extra imaging next to me.’ ”

Save images

But once you get it, don’t forget to keep it. “Many times you do an acquisition, you move the machine, and you realize you forget to save the image and now you’ve got to go back and do it all over again,” Dr. Farber lamented. But by once again making technology your friend, with functions that allow auto-return to previous positions, among other auto-commands, you can save the needed information and reduce any unnecessary dose exposure for both yourself and the patient, he said.

Protect your eyes

Cataracts are still all too common in the field, according to Dr. Farber. “It’s important that you have side shields on your glasses to cut down on the amount of radiation that comes in and around the glasses.” Eschew glasses that don’t overtly hug your face.

Geometric differences

Don’t forget that, if you’re standing on the side of the imaging source, the scattering effect will be greater than if you’re on the side of the image receptor. Once again, an understanding of the inverse square law can be protective, according to Dr. Kirkwood: “As x-rays exit the source, there is an exponential decrease in the number of x-rays per unit area as the distance from the source increases.”

“It’s simple stuff,” concluded Dr. Farber. “If you get in the habit of doing these things you will cut down your radiation exposure.”

Neither Dr. Farber nor Dr. Kirkwood had any relevant disclosures.

[email protected]
On Twitter @whitneymcknight

SCOTTSDALE, Ariz.– “It’s surprising to me today, when I go proctor or watch a case, how people don’t understand the impact of radiation,” Dr. Mark A. Farber, professor of surgery and radiology at the University of North Carolina, Chapel Hill, said at the Southern Association for Vascular Surgery annual meeting. “Many times, I see people’s hands underneath the machine and on the fluoroscopy image.”

This flouting of the so-called ALARA (as low as reasonably achievable) principle happens in part because the number of complex procedures performed by vascular surgeons is increasing, despite what presenter Dr. Melissa Kirkwood, a vascular surgeon at the University of Texas Southwestern Medical Center, Dallas, told the audience is a lack of training in radiation dose terminology and basic safety principles. Yet, practicing excellent radiation safety protocols is “paramount” according to Dr. Farber who, along with Dr. Kirkwood, shared insights on how to minimize dose to both patients and vascular specialists, whether it be from primary, leakage, or scatter radiation.

Table up, detector down

Minimizing the air gap by as little as 100 mm – from 700 mm to 600 mm, for example – can reduce the dose of radiation from 17%-29%, whereas a 
10-cm increase in the air gap can result in as much as a 20%-38% increase in the radiation skin dose. This is essentially the application of the inverse square law, according to Dr. Kirkwood.

Dr. Farber said that some of the newer, more advanced machines have sensors that automatically detect where the collector should be in relation to the patient, but if your machine doesn’t have these “bells and whistles … remember that the skin dose decreases as the air gap decreases.”

Another advantage to using new imaging systems, according to Dr. Farber, is that they allow the use of pulsed fluoroscopy for as few as 2 or 3 pulses/sec. The selected pulse rate determines the number of fluoroscopic image frames that are generated by the machine per second. This is significant when the dose savings are essential and when performing simpler procedures, he said. “If you go from 7.5 frames down to 3 frames/sec, you can decrease the exposure for both you and your patient.”

Use between 15 and 30 pulses/sec for critical procedures where precision is crucial, but reducing the rate to 7.5 pulses/sec may result in as much as 70% less of a skin dose.

Add radiation barriers

Don’t assume that the lead shielding is doing the job. “It’s important that you keep up on this and have it tested regularly,” said Dr. Farber, who recently discovered his thyroid shield was cracked and needed to be replaced. Also, consider the lead shielding of your staff, which, even if it is not used as frequently as the physician’s, can suffer from improper handling. “They fold it or crinkle it up and drop it on the floor. This can lead to problems,” he said. And be sure to remember leaded glasses, lead drapes for the sides of the table, and leaded ceiling-mounted or standing shields.

For extra protection, Dr. Farber recommended the use of disposable protective drapes with cut-outs that allow access to the patient while helping to reduce the amount of scatter radiation exposure to the operator’s limbs. At a tally of anywhere from 1 to 10 mGy/hour, scatter radiation emanating from the patient is a particular risk to the operator’s legs from the knees down, said Dr. Kirkwood, “depending on how tall you are.”

Using the disposable drapes also can result in a 12-fold decrease in the amount of scatter on the eyes, a 25-fold decrease in thyroid exposure to scatter, and a 29-fold decrease in the hands being exposed. “They can be cumbersome at times, I admit,” Dr. Farber said. “But there is no substitute for using protective drapes.”

Leaded aprons also help cut radiation transmission rates, even if they are not foolproof. Wearing two-piece leaded apron systems can help cut down the body strain from the weight of the aprons; however, Dr. Farber said that, at his institution, they use a suspended body shield system operated by a boom so there is no physical stress on the clinician. Because the weightless system also provides additional protection for the specialist’s head and limbs, Dr. Farber said that the hefty price tag is justified. “The way I sold it to the hospital was I told them I could stop doing procedures, or they could get me one of these systems so I could do more procedures,” he said, adding he is having a weightless system installed on each side of the table. “They’ll get their money’s worth by the fact that you’re not over your exposure limit.”

And finally, don’t forget to protect the anesthesiologist! A standing shield that gives broad coverage area should suffice, Dr. Farber said.

Alter the intensifier position

Altering the angle can help ensure that one area of the patient’s body isn’t being overexposed to radiation. Since previously irradiated skin reacts abnormally when re-exposed to radiation because the regeneration and repair of the dermis can take up to several weeks after the initial insult, the timing of the intervals between exposures is critical, said Dr. Kirkwood, adding that the Joint Commission recommended that all doses of fluoroscopically guided interventions performed within the past 6-12 months should be considered when assessing potential skin injury risk.

Use collimation

Making it tighter, for example, can help improve image quality and reduce the radiation dose to both the patient and the operator, as can varying the acquisition rates.

Exit the room during DSA

During digital subtraction angiography, Dr. Farber said to “get away from the table if you can! It’s a huge dose you don’t need to be exposed to if you don’t need to be right next to the machine.” Dr. Kirkwood agreed: “Angiography is 10-100 times more dose than fluoroscopy.”

Reduce magnification

Using a larger monitor allows the operator to see more detail without increasing the magnification, which also increases the dose in the amount of the diameter over the diameter squared. “By not magnifying up [from a field of view of 14 to 28], you will save yourself a factor of at least 4,” Dr. Farber said. “And the actual dose may be even less.”

Optimize imaging

Today’s advanced imaging systems make it easy to produce many high-quality images – CT scans and ultrasounds – that allow a more comprehensive picture. Having various image sources on screen at once is “practice changing” because it can help clinicians see more possibilities for “how to do the case,” said Dr. Farber. “I’ve never heard anyone say, ’Well, I wish I didn’t have that extra imaging next to me.’ ”

Save images

But once you get it, don’t forget to keep it. “Many times you do an acquisition, you move the machine, and you realize you forget to save the image and now you’ve got to go back and do it all over again,” Dr. Farber lamented. But by once again making technology your friend, with functions that allow auto-return to previous positions, among other auto-commands, you can save the needed information and reduce any unnecessary dose exposure for both yourself and the patient, he said.

Protect your eyes

Cataracts are still all too common in the field, according to Dr. Farber. “It’s important that you have side shields on your glasses to cut down on the amount of radiation that comes in and around the glasses.” Eschew glasses that don’t overtly hug your face.

Geometric differences

Don’t forget that, if you’re standing on the side of the imaging source, the scattering effect will be greater than if you’re on the side of the image receptor. Once again, an understanding of the inverse square law can be protective, according to Dr. Kirkwood: “As x-rays exit the source, there is an exponential decrease in the number of x-rays per unit area as the distance from the source increases.”

“It’s simple stuff,” concluded Dr. Farber. “If you get in the habit of doing these things you will cut down your radiation exposure.”

Neither Dr. Farber nor Dr. Kirkwood had any relevant disclosures.

[email protected]
On Twitter @whitneymcknight

CORONADO, CALIF. – About half of patients decide to undergo head and neck surgery even before meeting their surgeon, and concerns about cost of the procedure weigh heavily on their minds, results from a pilot study demonstrated.

In an effort to determine which factors influence patient decision making about elective surgery in otolaryngology, lead study author Dr. Maya G. Sardesai and her associates surveyed 48 consecutive adults who underwent head and neck surgery performed by one of six surgeons at Harborview Medical Center, Seattle, between March and September 2014.

The effort “rose from an observation in her clinical practice that, despite similar degrees of disease burden and similar counseling, patients sometimes show widely divergent degrees of enthusiasm for elective procedures,” Dr. Sardesai of the department of otolaryngology-head and neck surgery at the medical center said at the Triological Society’s Combined Sections Meeting. “This prompted the question: What information influences decision making in this setting?”

Current guidelines emphasize discussing the risks and benefits of surgery in the informed consent process, she continued, “but some studies of decision making in this setting have suggested that other factors might also influence decisions, such as family advice, social perception, and cost. There’s limited data in the otolaryngology literature about this, even though there’s a preponderance of quality-of-life surgery with low but potentially significant risks.”

With input from patients and surgeons, the researchers created a 35-question survey and administered it in the surgeon’s office, with questions that centered around the timing of the procedure, advice of others, sources of information, and their approach to decision making. More than half of patients (56%) were undergoing tonsillectomy, followed by a nasal procedure (48%), palate procedure (44%), midline glossectomy (35%), hyoid suspension (4%), genioglossus advancement (4%), laryngeal procedure (2%), and other (6%). (The numbers exceeded 100% because some patients underwent more than one procedure.)

Nearly half of subjects (49%) reported making their decision to pursue surgery even before their surgical consultation or meeting their surgeon. The researchers then divided the cohort into patients who had decided to pursue surgery before or after meeting their surgeon. Among those who made the decision before meeting the surgeon, 64% rated information they received from their primary care provider as very important, while 100% rated information they received from the surgeon as very important. These percentages were similar among patients who made the decision after meeting the surgeon (43% and 96%, respectively).

Patients who made their decision to pursue surgery after meeting their surgeon also were more likely to weigh information received from the Internet as more important, compared with patients who made their decision before meeting their surgeon (38% vs. 20%). “This difference was not statistically significant,” Dr. Sardesai said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons. “All patients felt that Internet information seemed important.”

Patients in both groups weighed concerns about symptoms as very important (in the range of 83%), which rated “highly if not more than concerns about the risks with or without surgery (70%).” Finally, she and her associates found that 49% of patients in both groups considered the cost of medical bills as very important, “which is an interesting finding, because our current consent process doesn’t include much discussion about monetary costs of treatment.”

Overall, the findings suggest that otolaryngologists and head and neck surgeons should reach out to referring providers “to ensure that they are well informed about the indications, benefits, limitation, and risks of head and neck surgeries,” Dr. Sardesai concluded. “This may also enhance opportunities for shared and collaborative decision making. If decisions are being made prior to consultation, it begs the question about whether there are potential surgery candidates who defer surgical consultation altogether, and thus may be missing opportunities for better care. As otolaryngologists, we should also take an active role in providing and curating information from the Internet, since this is currently likely an increasingly important source of information for patients.”

She acknowledged certain limitations of the study, including its small sample size and the potential for recall bias. In addition, the survey “was administered in a surgeon’s office, which might bias patients to overemphasize the role of the surgeon,” she said. “Our future plans are to administer an enhanced version of the survey to broader [practice settings] to better understand these differences.”

Dr. Sardesai reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – About half of patients decide to undergo head and neck surgery even before meeting their surgeon, and concerns about cost of the procedure weigh heavily on their minds, results from a pilot study demonstrated.

In an effort to determine which factors influence patient decision making about elective surgery in otolaryngology, lead study author Dr. Maya G. Sardesai and her associates surveyed 48 consecutive adults who underwent head and neck surgery performed by one of six surgeons at Harborview Medical Center, Seattle, between March and September 2014.

The effort “rose from an observation in her clinical practice that, despite similar degrees of disease burden and similar counseling, patients sometimes show widely divergent degrees of enthusiasm for elective procedures,” Dr. Sardesai of the department of otolaryngology-head and neck surgery at the medical center said at the Triological Society’s Combined Sections Meeting. “This prompted the question: What information influences decision making in this setting?”

Current guidelines emphasize discussing the risks and benefits of surgery in the informed consent process, she continued, “but some studies of decision making in this setting have suggested that other factors might also influence decisions, such as family advice, social perception, and cost. There’s limited data in the otolaryngology literature about this, even though there’s a preponderance of quality-of-life surgery with low but potentially significant risks.”

With input from patients and surgeons, the researchers created a 35-question survey and administered it in the surgeon’s office, with questions that centered around the timing of the procedure, advice of others, sources of information, and their approach to decision making. More than half of patients (56%) were undergoing tonsillectomy, followed by a nasal procedure (48%), palate procedure (44%), midline glossectomy (35%), hyoid suspension (4%), genioglossus advancement (4%), laryngeal procedure (2%), and other (6%). (The numbers exceeded 100% because some patients underwent more than one procedure.)

Nearly half of subjects (49%) reported making their decision to pursue surgery even before their surgical consultation or meeting their surgeon. The researchers then divided the cohort into patients who had decided to pursue surgery before or after meeting their surgeon. Among those who made the decision before meeting the surgeon, 64% rated information they received from their primary care provider as very important, while 100% rated information they received from the surgeon as very important. These percentages were similar among patients who made the decision after meeting the surgeon (43% and 96%, respectively).

Patients who made their decision to pursue surgery after meeting their surgeon also were more likely to weigh information received from the Internet as more important, compared with patients who made their decision before meeting their surgeon (38% vs. 20%). “This difference was not statistically significant,” Dr. Sardesai said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons. “All patients felt that Internet information seemed important.”

Patients in both groups weighed concerns about symptoms as very important (in the range of 83%), which rated “highly if not more than concerns about the risks with or without surgery (70%).” Finally, she and her associates found that 49% of patients in both groups considered the cost of medical bills as very important, “which is an interesting finding, because our current consent process doesn’t include much discussion about monetary costs of treatment.”

Overall, the findings suggest that otolaryngologists and head and neck surgeons should reach out to referring providers “to ensure that they are well informed about the indications, benefits, limitation, and risks of head and neck surgeries,” Dr. Sardesai concluded. “This may also enhance opportunities for shared and collaborative decision making. If decisions are being made prior to consultation, it begs the question about whether there are potential surgery candidates who defer surgical consultation altogether, and thus may be missing opportunities for better care. As otolaryngologists, we should also take an active role in providing and curating information from the Internet, since this is currently likely an increasingly important source of information for patients.”

She acknowledged certain limitations of the study, including its small sample size and the potential for recall bias. In addition, the survey “was administered in a surgeon’s office, which might bias patients to overemphasize the role of the surgeon,” she said. “Our future plans are to administer an enhanced version of the survey to broader [practice settings] to better understand these differences.”

Dr. Sardesai reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – About half of patients decide to undergo head and neck surgery even before meeting their surgeon, and concerns about cost of the procedure weigh heavily on their minds, results from a pilot study demonstrated.

In an effort to determine which factors influence patient decision making about elective surgery in otolaryngology, lead study author Dr. Maya G. Sardesai and her associates surveyed 48 consecutive adults who underwent head and neck surgery performed by one of six surgeons at Harborview Medical Center, Seattle, between March and September 2014.

The effort “rose from an observation in her clinical practice that, despite similar degrees of disease burden and similar counseling, patients sometimes show widely divergent degrees of enthusiasm for elective procedures,” Dr. Sardesai of the department of otolaryngology-head and neck surgery at the medical center said at the Triological Society’s Combined Sections Meeting. “This prompted the question: What information influences decision making in this setting?”

Current guidelines emphasize discussing the risks and benefits of surgery in the informed consent process, she continued, “but some studies of decision making in this setting have suggested that other factors might also influence decisions, such as family advice, social perception, and cost. There’s limited data in the otolaryngology literature about this, even though there’s a preponderance of quality-of-life surgery with low but potentially significant risks.”

With input from patients and surgeons, the researchers created a 35-question survey and administered it in the surgeon’s office, with questions that centered around the timing of the procedure, advice of others, sources of information, and their approach to decision making. More than half of patients (56%) were undergoing tonsillectomy, followed by a nasal procedure (48%), palate procedure (44%), midline glossectomy (35%), hyoid suspension (4%), genioglossus advancement (4%), laryngeal procedure (2%), and other (6%). (The numbers exceeded 100% because some patients underwent more than one procedure.)

Nearly half of subjects (49%) reported making their decision to pursue surgery even before their surgical consultation or meeting their surgeon. The researchers then divided the cohort into patients who had decided to pursue surgery before or after meeting their surgeon. Among those who made the decision before meeting the surgeon, 64% rated information they received from their primary care provider as very important, while 100% rated information they received from the surgeon as very important. These percentages were similar among patients who made the decision after meeting the surgeon (43% and 96%, respectively).

Patients who made their decision to pursue surgery after meeting their surgeon also were more likely to weigh information received from the Internet as more important, compared with patients who made their decision before meeting their surgeon (38% vs. 20%). “This difference was not statistically significant,” Dr. Sardesai said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons. “All patients felt that Internet information seemed important.”

Patients in both groups weighed concerns about symptoms as very important (in the range of 83%), which rated “highly if not more than concerns about the risks with or without surgery (70%).” Finally, she and her associates found that 49% of patients in both groups considered the cost of medical bills as very important, “which is an interesting finding, because our current consent process doesn’t include much discussion about monetary costs of treatment.”

Overall, the findings suggest that otolaryngologists and head and neck surgeons should reach out to referring providers “to ensure that they are well informed about the indications, benefits, limitation, and risks of head and neck surgeries,” Dr. Sardesai concluded. “This may also enhance opportunities for shared and collaborative decision making. If decisions are being made prior to consultation, it begs the question about whether there are potential surgery candidates who defer surgical consultation altogether, and thus may be missing opportunities for better care. As otolaryngologists, we should also take an active role in providing and curating information from the Internet, since this is currently likely an increasingly important source of information for patients.”

She acknowledged certain limitations of the study, including its small sample size and the potential for recall bias. In addition, the survey “was administered in a surgeon’s office, which might bias patients to overemphasize the role of the surgeon,” she said. “Our future plans are to administer an enhanced version of the survey to broader [practice settings] to better understand these differences.”

Dr. Sardesai reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

Yuankai Shi, MD, PhD

Photo by Larry Young

SAN FRANCISCO—The histone deacetylase (HDAC) inhibitor chidamide is effective and well-tolerated in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), results of the phase 2 CHIPEL trial suggest.

The study showed that chidamide can elicit higher response rates than those previously observed with the folate analog metabolic inhibitor pralatrexate and the HDAC inhibitor romidepsin.

Chidamide also prolonged survival and posed a lower risk of toxicity compared to pralatrexate and romidepsin.

Yuankai Shi, MD, PhD, of the Chinese Academy of Medical Science & Peking Union Medical College in  Beijing, China, presented these results at the 7th Annual T-cell Lymphoma Forum. The trial is sponsored by Chipscreen Biosciences Ltd.

He noted that the CHIPEL study was split into two parts: an exploratory trial and a pivotal trial.

Exploratory trial

The exploratory trial included 19 patients who had a median age of 51 and were a median of 1.41 years from diagnosis. Seventeen patients had PTCL unspecified (PTCL-U), and 2 had other subtypes of PTCL.

The patients received chidamide at 30 mg (n=9) or 50 mg (n=10) twice a week for 2 weeks of a 3-week cycle. The overall response rate was 26% (n=5), and 16% of patients (n=3) had a complete response (CR) or unconfirmed CR (CRu).

Pivotal trial

The pivotal trial included 83 patients who had a median age of 53 and were a median of 1.06 years from diagnosis.

The patients had PTCL-U (29.1%, n=23), nasal NK/T-cell lymphoma (20.3%, n=16), anaplastic large-cell lymphoma (ALCL, 20.3%, n=16), angioimmunoblastic T-cell lymphoma (AITL, 11.4%, n=9), enteropathy-type T-cell lymphoma (2.5%, n=2), CD4-positive PTCL (1.3%, n=1), Lennert-type PTCL (1.3%, n=1), transformed mycosis fungoides (1.3%, n=1), and other subtypes of PTCL (12.7%, n=10).

These patients received chidamide at 30 mg twice a week without a drug-free holiday.

The overall response rate was 29% (n=23) according to investigators and 28% (n=22) according to an independent review committee. Fourteen percent of patients (n=11) had a CR/CRu, according to both sources.

The median progression-free survival was 2.1 months for all patients, 14 months for patients who achieved CR/CRus, 7.7 months in patients with partial responses, and 2.5 months in patients with stable disease.

The median overall survival was 21.4 months in all patients and not reached in patients who had a CR/CRu, partial response, or stable disease.

Overall safety

Of all 102 patients (in both the pivotal and exploratory analyses), 80% had at least one adverse event (AE), 37% had grade 3 or higher AEs, 17% had AEs leading to treatment discontinuation, and 8% had severe AEs.

The most common AEs were thrombocytopenia (50%), leukopenia (37%), neutropenia (19%), fatigue (11%), and fever (11%).

Twenty-four percent of patients had grade 3 or higher thrombocytopenia, 13% had grade 3 or higher leukopenia, and 10% had grade 3 or higher neutropenia.

Chidamide vs other agents

Dr Shi compared response rates with chidamide in the pivotal trial to those previously observed with pralatrexate (O’Connor et al, JCO 2011) and romidepsin (Coiffier et al, J Hematol Oncol 2014).

In patients with PTCL-U, response rates were similar for all 3 drugs (≈30%). In ALCL, the response rate with chidamide was higher (≈50%) than with pralatrexate (≈30%) or romidepsin (≈25%). And in AITL, the response rate with chidamide was higher (≈45%) than with pralatrexate (≈8%) or romidepsin (≈30%).

Chidamide also conferred better overall survival than pralatrexate, romidepsin, and other treatments from previous studies.

The median overall survival was 6.5 months with chemotherapy (Mak et al, JCO 2013), 14.5 months with pralatrexate (O’Connor et al, JCO 2011), 11.3 months with romidepsin (Coiffier et al, J Hematol Oncol 2014), 7.9 months with belinostat (Hyon-Zu Lee, Clinical Review 2009), and 21.4 months with chidamide.

Finally, Dr Shi compared the rates of AEs observed in the chidamide pivotal trial to AEs observed in the pralatrexate and romidepsin trials.

At least one AE occurred in 100% of patients treated with pralatrexate, 96% of patients on romidepsin, and 82% of patients on chidamide. Grade 3 or higher AEs occurred in 74%, 66%, and 39% of patients, respectively. And at least one severe AE occurred in 44%, 46%, and 8% of patients, respectively.

The favorable results observed with chidamide support the Chinese Food and Drug Administration’s December decision to approve the drug (under the brand name Epidaza) for use in patients with PTCL.

Yuankai Shi, MD, PhD

Photo by Larry Young

SAN FRANCISCO—The histone deacetylase (HDAC) inhibitor chidamide is effective and well-tolerated in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), results of the phase 2 CHIPEL trial suggest.

The study showed that chidamide can elicit higher response rates than those previously observed with the folate analog metabolic inhibitor pralatrexate and the HDAC inhibitor romidepsin.

Chidamide also prolonged survival and posed a lower risk of toxicity compared to pralatrexate and romidepsin.

Yuankai Shi, MD, PhD, of the Chinese Academy of Medical Science & Peking Union Medical College in  Beijing, China, presented these results at the 7th Annual T-cell Lymphoma Forum. The trial is sponsored by Chipscreen Biosciences Ltd.

He noted that the CHIPEL study was split into two parts: an exploratory trial and a pivotal trial.

Exploratory trial

The exploratory trial included 19 patients who had a median age of 51 and were a median of 1.41 years from diagnosis. Seventeen patients had PTCL unspecified (PTCL-U), and 2 had other subtypes of PTCL.

The patients received chidamide at 30 mg (n=9) or 50 mg (n=10) twice a week for 2 weeks of a 3-week cycle. The overall response rate was 26% (n=5), and 16% of patients (n=3) had a complete response (CR) or unconfirmed CR (CRu).

Pivotal trial

The pivotal trial included 83 patients who had a median age of 53 and were a median of 1.06 years from diagnosis.

The patients had PTCL-U (29.1%, n=23), nasal NK/T-cell lymphoma (20.3%, n=16), anaplastic large-cell lymphoma (ALCL, 20.3%, n=16), angioimmunoblastic T-cell lymphoma (AITL, 11.4%, n=9), enteropathy-type T-cell lymphoma (2.5%, n=2), CD4-positive PTCL (1.3%, n=1), Lennert-type PTCL (1.3%, n=1), transformed mycosis fungoides (1.3%, n=1), and other subtypes of PTCL (12.7%, n=10).

These patients received chidamide at 30 mg twice a week without a drug-free holiday.

The overall response rate was 29% (n=23) according to investigators and 28% (n=22) according to an independent review committee. Fourteen percent of patients (n=11) had a CR/CRu, according to both sources.

The median progression-free survival was 2.1 months for all patients, 14 months for patients who achieved CR/CRus, 7.7 months in patients with partial responses, and 2.5 months in patients with stable disease.

The median overall survival was 21.4 months in all patients and not reached in patients who had a CR/CRu, partial response, or stable disease.

Overall safety

Of all 102 patients (in both the pivotal and exploratory analyses), 80% had at least one adverse event (AE), 37% had grade 3 or higher AEs, 17% had AEs leading to treatment discontinuation, and 8% had severe AEs.

The most common AEs were thrombocytopenia (50%), leukopenia (37%), neutropenia (19%), fatigue (11%), and fever (11%).

Twenty-four percent of patients had grade 3 or higher thrombocytopenia, 13% had grade 3 or higher leukopenia, and 10% had grade 3 or higher neutropenia.

Chidamide vs other agents

Dr Shi compared response rates with chidamide in the pivotal trial to those previously observed with pralatrexate (O’Connor et al, JCO 2011) and romidepsin (Coiffier et al, J Hematol Oncol 2014).

In patients with PTCL-U, response rates were similar for all 3 drugs (≈30%). In ALCL, the response rate with chidamide was higher (≈50%) than with pralatrexate (≈30%) or romidepsin (≈25%). And in AITL, the response rate with chidamide was higher (≈45%) than with pralatrexate (≈8%) or romidepsin (≈30%).

Chidamide also conferred better overall survival than pralatrexate, romidepsin, and other treatments from previous studies.

The median overall survival was 6.5 months with chemotherapy (Mak et al, JCO 2013), 14.5 months with pralatrexate (O’Connor et al, JCO 2011), 11.3 months with romidepsin (Coiffier et al, J Hematol Oncol 2014), 7.9 months with belinostat (Hyon-Zu Lee, Clinical Review 2009), and 21.4 months with chidamide.

Finally, Dr Shi compared the rates of AEs observed in the chidamide pivotal trial to AEs observed in the pralatrexate and romidepsin trials.

At least one AE occurred in 100% of patients treated with pralatrexate, 96% of patients on romidepsin, and 82% of patients on chidamide. Grade 3 or higher AEs occurred in 74%, 66%, and 39% of patients, respectively. And at least one severe AE occurred in 44%, 46%, and 8% of patients, respectively.

The favorable results observed with chidamide support the Chinese Food and Drug Administration’s December decision to approve the drug (under the brand name Epidaza) for use in patients with PTCL.

Yuankai Shi, MD, PhD

Photo by Larry Young

SAN FRANCISCO—The histone deacetylase (HDAC) inhibitor chidamide is effective and well-tolerated in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), results of the phase 2 CHIPEL trial suggest.

The study showed that chidamide can elicit higher response rates than those previously observed with the folate analog metabolic inhibitor pralatrexate and the HDAC inhibitor romidepsin.

Chidamide also prolonged survival and posed a lower risk of toxicity compared to pralatrexate and romidepsin.

Yuankai Shi, MD, PhD, of the Chinese Academy of Medical Science & Peking Union Medical College in  Beijing, China, presented these results at the 7th Annual T-cell Lymphoma Forum. The trial is sponsored by Chipscreen Biosciences Ltd.

He noted that the CHIPEL study was split into two parts: an exploratory trial and a pivotal trial.

Exploratory trial

The exploratory trial included 19 patients who had a median age of 51 and were a median of 1.41 years from diagnosis. Seventeen patients had PTCL unspecified (PTCL-U), and 2 had other subtypes of PTCL.

The patients received chidamide at 30 mg (n=9) or 50 mg (n=10) twice a week for 2 weeks of a 3-week cycle. The overall response rate was 26% (n=5), and 16% of patients (n=3) had a complete response (CR) or unconfirmed CR (CRu).

Pivotal trial

The pivotal trial included 83 patients who had a median age of 53 and were a median of 1.06 years from diagnosis.

The patients had PTCL-U (29.1%, n=23), nasal NK/T-cell lymphoma (20.3%, n=16), anaplastic large-cell lymphoma (ALCL, 20.3%, n=16), angioimmunoblastic T-cell lymphoma (AITL, 11.4%, n=9), enteropathy-type T-cell lymphoma (2.5%, n=2), CD4-positive PTCL (1.3%, n=1), Lennert-type PTCL (1.3%, n=1), transformed mycosis fungoides (1.3%, n=1), and other subtypes of PTCL (12.7%, n=10).

These patients received chidamide at 30 mg twice a week without a drug-free holiday.

The overall response rate was 29% (n=23) according to investigators and 28% (n=22) according to an independent review committee. Fourteen percent of patients (n=11) had a CR/CRu, according to both sources.

The median progression-free survival was 2.1 months for all patients, 14 months for patients who achieved CR/CRus, 7.7 months in patients with partial responses, and 2.5 months in patients with stable disease.

The median overall survival was 21.4 months in all patients and not reached in patients who had a CR/CRu, partial response, or stable disease.

Overall safety

Of all 102 patients (in both the pivotal and exploratory analyses), 80% had at least one adverse event (AE), 37% had grade 3 or higher AEs, 17% had AEs leading to treatment discontinuation, and 8% had severe AEs.

The most common AEs were thrombocytopenia (50%), leukopenia (37%), neutropenia (19%), fatigue (11%), and fever (11%).

Twenty-four percent of patients had grade 3 or higher thrombocytopenia, 13% had grade 3 or higher leukopenia, and 10% had grade 3 or higher neutropenia.

Chidamide vs other agents

Dr Shi compared response rates with chidamide in the pivotal trial to those previously observed with pralatrexate (O’Connor et al, JCO 2011) and romidepsin (Coiffier et al, J Hematol Oncol 2014).

In patients with PTCL-U, response rates were similar for all 3 drugs (≈30%). In ALCL, the response rate with chidamide was higher (≈50%) than with pralatrexate (≈30%) or romidepsin (≈25%). And in AITL, the response rate with chidamide was higher (≈45%) than with pralatrexate (≈8%) or romidepsin (≈30%).

Chidamide also conferred better overall survival than pralatrexate, romidepsin, and other treatments from previous studies.

The median overall survival was 6.5 months with chemotherapy (Mak et al, JCO 2013), 14.5 months with pralatrexate (O’Connor et al, JCO 2011), 11.3 months with romidepsin (Coiffier et al, J Hematol Oncol 2014), 7.9 months with belinostat (Hyon-Zu Lee, Clinical Review 2009), and 21.4 months with chidamide.

Finally, Dr Shi compared the rates of AEs observed in the chidamide pivotal trial to AEs observed in the pralatrexate and romidepsin trials.

At least one AE occurred in 100% of patients treated with pralatrexate, 96% of patients on romidepsin, and 82% of patients on chidamide. Grade 3 or higher AEs occurred in 74%, 66%, and 39% of patients, respectively. And at least one severe AE occurred in 44%, 46%, and 8% of patients, respectively.

The favorable results observed with chidamide support the Chinese Food and Drug Administration’s December decision to approve the drug (under the brand name Epidaza) for use in patients with PTCL.

Thrombus

Credit: Kevin MacKenzie

Corticosteroid use may increase the risk of venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD), according to a study published in Clinical Gastroenterology and Hepatology.

The study showed that IBD patients who received corticosteroids alone or in combination with biologic therapy had a significantly higher risk of developing VTE than patients who received only biologic therapy.

“Venous thromboembolism is common in IBD and can lead to significant morbidity, increased death, and high rates of recurrent blood clots,” said lead study author Peter D.R. Higgins, MD, PhD, of the University of Michigan in Ann Arbor.

“The importance of understanding what causes this complication in this patient group cannot be understated.”

With that in mind, Dr Higgins and his colleagues conducted a retrospective analysis of adults with IBD identified from the Truven Health MarketScan® Databases.

The researchers assessed the rates of VTE over a 12-month period in 15,100 patients who were treated with biologics, corticosteroids, or a combination of the two.

In all, there were 325 VTEs. They occurred in 2.25% of patients who received only corticosteroids, 0.44% of patients who received biologics only, and 2.49% of patients who received combination therapy.

So the unadjusted risk of VTE within 12 months of an index prescription was 5-fold higher in patients who received corticosteroids alone and in combination with biologics than in patients who received biologics alone (P=0.028).

In a multivariate analysis in which corticosteroid-treated patients served as the reference, the odds ratio for VTE was 0.21 in patients who received biologics only (P<0.05) and 1.01 in patients treated with combination therapy (no significant difference).

“Combination therapy with corticosteroids and biologics was associated with nearly the same risk as corticosteroids alone, validating our conclusion that corticosteroids may truly increase venous thromboembolism risk and eliminate the potential benefit (for venous thromboembolic events) of inducing remission with biologics alone,” Dr Higgins said.

He and his colleagues noted that, although the association between active IBD flares and VTE has been well established, this is the first study to show a strong, independent association between corticosteroid use and VTE.

The study was funded by AbbVie Inc.

Thrombus

Credit: Kevin MacKenzie

Corticosteroid use may increase the risk of venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD), according to a study published in Clinical Gastroenterology and Hepatology.

The study showed that IBD patients who received corticosteroids alone or in combination with biologic therapy had a significantly higher risk of developing VTE than patients who received only biologic therapy.

“Venous thromboembolism is common in IBD and can lead to significant morbidity, increased death, and high rates of recurrent blood clots,” said lead study author Peter D.R. Higgins, MD, PhD, of the University of Michigan in Ann Arbor.

“The importance of understanding what causes this complication in this patient group cannot be understated.”

With that in mind, Dr Higgins and his colleagues conducted a retrospective analysis of adults with IBD identified from the Truven Health MarketScan® Databases.

The researchers assessed the rates of VTE over a 12-month period in 15,100 patients who were treated with biologics, corticosteroids, or a combination of the two.

In all, there were 325 VTEs. They occurred in 2.25% of patients who received only corticosteroids, 0.44% of patients who received biologics only, and 2.49% of patients who received combination therapy.

So the unadjusted risk of VTE within 12 months of an index prescription was 5-fold higher in patients who received corticosteroids alone and in combination with biologics than in patients who received biologics alone (P=0.028).

In a multivariate analysis in which corticosteroid-treated patients served as the reference, the odds ratio for VTE was 0.21 in patients who received biologics only (P<0.05) and 1.01 in patients treated with combination therapy (no significant difference).

“Combination therapy with corticosteroids and biologics was associated with nearly the same risk as corticosteroids alone, validating our conclusion that corticosteroids may truly increase venous thromboembolism risk and eliminate the potential benefit (for venous thromboembolic events) of inducing remission with biologics alone,” Dr Higgins said.

He and his colleagues noted that, although the association between active IBD flares and VTE has been well established, this is the first study to show a strong, independent association between corticosteroid use and VTE.

The study was funded by AbbVie Inc.

Thrombus

Credit: Kevin MacKenzie

Corticosteroid use may increase the risk of venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD), according to a study published in Clinical Gastroenterology and Hepatology.

The study showed that IBD patients who received corticosteroids alone or in combination with biologic therapy had a significantly higher risk of developing VTE than patients who received only biologic therapy.

“Venous thromboembolism is common in IBD and can lead to significant morbidity, increased death, and high rates of recurrent blood clots,” said lead study author Peter D.R. Higgins, MD, PhD, of the University of Michigan in Ann Arbor.

“The importance of understanding what causes this complication in this patient group cannot be understated.”

With that in mind, Dr Higgins and his colleagues conducted a retrospective analysis of adults with IBD identified from the Truven Health MarketScan® Databases.

The researchers assessed the rates of VTE over a 12-month period in 15,100 patients who were treated with biologics, corticosteroids, or a combination of the two.

In all, there were 325 VTEs. They occurred in 2.25% of patients who received only corticosteroids, 0.44% of patients who received biologics only, and 2.49% of patients who received combination therapy.

So the unadjusted risk of VTE within 12 months of an index prescription was 5-fold higher in patients who received corticosteroids alone and in combination with biologics than in patients who received biologics alone (P=0.028).

In a multivariate analysis in which corticosteroid-treated patients served as the reference, the odds ratio for VTE was 0.21 in patients who received biologics only (P<0.05) and 1.01 in patients treated with combination therapy (no significant difference).

“Combination therapy with corticosteroids and biologics was associated with nearly the same risk as corticosteroids alone, validating our conclusion that corticosteroids may truly increase venous thromboembolism risk and eliminate the potential benefit (for venous thromboembolic events) of inducing remission with biologics alone,” Dr Higgins said.

He and his colleagues noted that, although the association between active IBD flares and VTE has been well established, this is the first study to show a strong, independent association between corticosteroid use and VTE.

The study was funded by AbbVie Inc.

Platelets for transfusion

Platelet transfusions may not be appropriate treatment for patients with traumatic brain injury (TBI), new research suggests.

More than 1.7 million people in the US suffer a TBI every year, and as many as half of them experience progression of bleeding inside or around the brain, which is associated with an increased risk of death.

Platelet transfusions and desmopressin (DDAVP) are commonly used to prevent bleeding—and therefore death—in these patients.

But a new study published in the Journal of Neurotrauma suggests neither treatment is effective.

“Previous studies of platelet transfusion have looked only at mortality, and few studies have addressed the effect of DDAVP on bleeding in patients with TBI,” said study author Dennis Yong Kim, MD, of LA BioMed in Los Angeles, California.

“Our study found that the administration of platelets and DDAVP is no more effective in preventing progression of hemorrhage or death than was the use of none of these medications, irrespective of whether or not patients were on antiplatelet medications, such as aspirin, prior to their TBI.”

“Given the limited availability and potential for complications associated with transfusion of blood products like platelets, we believe that physicians should take a step back and re-think the necessity and efficacy of such treatments in patients with TBI.”

Dr Kim and his colleagues conducted a 3-year retrospective study of patients admitted to a Level 1 trauma center with TBI between January 1, 2010, and December 31, 2012. Of 408 patients, 126 received platelet transfusions and DDAVP, and 282 did not.

Overall, 37% of the patients demonstrated progression of traumatic intracranial hemorrhage within 4 hours of admission.

The researchers compared outcomes for the patients who received platelet transfusions and DDAVP to patients who did not receive the therapies.

A univariate analysis showed no difference in the incidence of hemorrhage progression, which occurred in 43.7% of patients who received transfusions and DDAVP and 34.2% of patients who received neither treatment (P=0.07).

And multivariate analyses showed that platelet transfusions and DDAVP were not associated with a decreased risk of hemorrhage progression (odds ratio=1.40, P=0.2) or mortality (odds ratio=1.50, P=0.4).

Platelets for transfusion

Platelet transfusions may not be appropriate treatment for patients with traumatic brain injury (TBI), new research suggests.

More than 1.7 million people in the US suffer a TBI every year, and as many as half of them experience progression of bleeding inside or around the brain, which is associated with an increased risk of death.

Platelet transfusions and desmopressin (DDAVP) are commonly used to prevent bleeding—and therefore death—in these patients.

But a new study published in the Journal of Neurotrauma suggests neither treatment is effective.

“Previous studies of platelet transfusion have looked only at mortality, and few studies have addressed the effect of DDAVP on bleeding in patients with TBI,” said study author Dennis Yong Kim, MD, of LA BioMed in Los Angeles, California.

“Our study found that the administration of platelets and DDAVP is no more effective in preventing progression of hemorrhage or death than was the use of none of these medications, irrespective of whether or not patients were on antiplatelet medications, such as aspirin, prior to their TBI.”

“Given the limited availability and potential for complications associated with transfusion of blood products like platelets, we believe that physicians should take a step back and re-think the necessity and efficacy of such treatments in patients with TBI.”

Dr Kim and his colleagues conducted a 3-year retrospective study of patients admitted to a Level 1 trauma center with TBI between January 1, 2010, and December 31, 2012. Of 408 patients, 126 received platelet transfusions and DDAVP, and 282 did not.

Overall, 37% of the patients demonstrated progression of traumatic intracranial hemorrhage within 4 hours of admission.

The researchers compared outcomes for the patients who received platelet transfusions and DDAVP to patients who did not receive the therapies.

A univariate analysis showed no difference in the incidence of hemorrhage progression, which occurred in 43.7% of patients who received transfusions and DDAVP and 34.2% of patients who received neither treatment (P=0.07).

And multivariate analyses showed that platelet transfusions and DDAVP were not associated with a decreased risk of hemorrhage progression (odds ratio=1.40, P=0.2) or mortality (odds ratio=1.50, P=0.4).

Platelets for transfusion

Platelet transfusions may not be appropriate treatment for patients with traumatic brain injury (TBI), new research suggests.

More than 1.7 million people in the US suffer a TBI every year, and as many as half of them experience progression of bleeding inside or around the brain, which is associated with an increased risk of death.

Platelet transfusions and desmopressin (DDAVP) are commonly used to prevent bleeding—and therefore death—in these patients.

But a new study published in the Journal of Neurotrauma suggests neither treatment is effective.

“Previous studies of platelet transfusion have looked only at mortality, and few studies have addressed the effect of DDAVP on bleeding in patients with TBI,” said study author Dennis Yong Kim, MD, of LA BioMed in Los Angeles, California.

“Our study found that the administration of platelets and DDAVP is no more effective in preventing progression of hemorrhage or death than was the use of none of these medications, irrespective of whether or not patients were on antiplatelet medications, such as aspirin, prior to their TBI.”

“Given the limited availability and potential for complications associated with transfusion of blood products like platelets, we believe that physicians should take a step back and re-think the necessity and efficacy of such treatments in patients with TBI.”

Dr Kim and his colleagues conducted a 3-year retrospective study of patients admitted to a Level 1 trauma center with TBI between January 1, 2010, and December 31, 2012. Of 408 patients, 126 received platelet transfusions and DDAVP, and 282 did not.

Overall, 37% of the patients demonstrated progression of traumatic intracranial hemorrhage within 4 hours of admission.

The researchers compared outcomes for the patients who received platelet transfusions and DDAVP to patients who did not receive the therapies.

A univariate analysis showed no difference in the incidence of hemorrhage progression, which occurred in 43.7% of patients who received transfusions and DDAVP and 34.2% of patients who received neither treatment (P=0.07).

And multivariate analyses showed that platelet transfusions and DDAVP were not associated with a decreased risk of hemorrhage progression (odds ratio=1.40, P=0.2) or mortality (odds ratio=1.50, P=0.4).

Eculizumab (Solirus)

Credit: Globovision

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending eculizumab (Soliris) as a treatment for atypical hemolytic uremic syndrome (aHUS), but only if certain conditions are met.

The guidance is the first to be produced as part of NICE’s highly specialized technologies program to evaluate treatments for very rare conditions.

aHUS affects around 200 people in England, with 20 to 30 new patients diagnosed with the condition each year.

The condition causes inflammation of blood vessels and thrombus formation throughout the body. So aHUS patients are at constant risk of sudden and progressive damage to, and failure of, vital organs.

“aHUS is a very distressing condition that imposes a significant burden both on those with the condition and their carers and families,” said NICE Chief Executive Sir Andrew Dillon.

“[A committee advising NICE] accepted that eculizumab is a step change in the management of aHUS and can be considered a significant innovation for a disease with a high unmet clinical need. It offers people with aHUS the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”

“The drug is, however, very expensive. The committee felt that the budget impact of eculizumab would be lower if the potential for adjusting the dose of the drug and stopping treatment was explored. This is reflected in the guidance, which recommends eculizumab should be funded only if important conditions are met, including the development of rules for starting and stopping treatment for clinical reasons. In the meantime, NHS England and the company should consider what opportunities might exist to reduce the cost of eculizumab to the NHS.”

The conditions for funding eculizumab are as follows:

• Use of the drug must be coordinated through an expert center.
• Monitoring systems must record the number of people with aHUS, the number who receive eculizumab, and the dose and duration of treatment.
• A national protocol must be developed for starting and stopping eculizumab for clinical reasons.
• A research program is needed with robust methods to evaluate when stopping treatment or dose adjustment might occur.

Eculizumab usage and costs

Eculizumab is given intravenously in adults as initial treatment at a dose of 900 mg for 4 weeks, then as maintenance treatment at a dose of 1200 mg on week 5 and then every 12 to 16 days.

The summary of product characteristics for eculizumab states that “treatment is recommended to continue for a patient’s lifetime, unless discontinuation of treatment is clinically indicated.” Eculizumab costs £3150 per 30 mL vial (excluding tax).

The net budget impact of eculizumab is confidential. However, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information that is available in the public domain.

This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult) and assumes a patient cohort of 170, as estimated by NHS England.

If it is assumed that all of these adults with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.

If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2, assuming all new patients are treated and all existing patients continue to be treated at the maintenance cost of £327,600 per year.

Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).

NHS England has indicated that the amount of the budget allocated for highly specialized services in 2013/14 was £544 million, and the money spent on high-cost drugs was £156 million.

The committee acknowledged that the estimate of the incremental cost of eculizumab made by Alexion Pharmaceuticals (the company developing eculizumab) compared with standard care was considerable. And incremental costs estimated by the evidence review group were higher still (although results are confidential).

Alexion estimated that eculizumab produced 25.22 additional quality-adjusted life-years (QALYs) per patient compared with standard care. Although the QALYs estimated in the evidence review group’s analysis were markedly lower than those calculated by the company, the advisory committee said both analyses produced substantial QALY gains of a magnitude that is rarely seen for any new drug.

For more information, see the guidance on the NICE website.

Eculizumab (Solirus)

Credit: Globovision

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending eculizumab (Soliris) as a treatment for atypical hemolytic uremic syndrome (aHUS), but only if certain conditions are met.

The guidance is the first to be produced as part of NICE’s highly specialized technologies program to evaluate treatments for very rare conditions.

aHUS affects around 200 people in England, with 20 to 30 new patients diagnosed with the condition each year.

The condition causes inflammation of blood vessels and thrombus formation throughout the body. So aHUS patients are at constant risk of sudden and progressive damage to, and failure of, vital organs.

“aHUS is a very distressing condition that imposes a significant burden both on those with the condition and their carers and families,” said NICE Chief Executive Sir Andrew Dillon.

“[A committee advising NICE] accepted that eculizumab is a step change in the management of aHUS and can be considered a significant innovation for a disease with a high unmet clinical need. It offers people with aHUS the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”

“The drug is, however, very expensive. The committee felt that the budget impact of eculizumab would be lower if the potential for adjusting the dose of the drug and stopping treatment was explored. This is reflected in the guidance, which recommends eculizumab should be funded only if important conditions are met, including the development of rules for starting and stopping treatment for clinical reasons. In the meantime, NHS England and the company should consider what opportunities might exist to reduce the cost of eculizumab to the NHS.”

The conditions for funding eculizumab are as follows:

• Use of the drug must be coordinated through an expert center.
• Monitoring systems must record the number of people with aHUS, the number who receive eculizumab, and the dose and duration of treatment.
• A national protocol must be developed for starting and stopping eculizumab for clinical reasons.
• A research program is needed with robust methods to evaluate when stopping treatment or dose adjustment might occur.

Eculizumab usage and costs

Eculizumab is given intravenously in adults as initial treatment at a dose of 900 mg for 4 weeks, then as maintenance treatment at a dose of 1200 mg on week 5 and then every 12 to 16 days.

The summary of product characteristics for eculizumab states that “treatment is recommended to continue for a patient’s lifetime, unless discontinuation of treatment is clinically indicated.” Eculizumab costs £3150 per 30 mL vial (excluding tax).

The net budget impact of eculizumab is confidential. However, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information that is available in the public domain.

This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult) and assumes a patient cohort of 170, as estimated by NHS England.

If it is assumed that all of these adults with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.

If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2, assuming all new patients are treated and all existing patients continue to be treated at the maintenance cost of £327,600 per year.

Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).

NHS England has indicated that the amount of the budget allocated for highly specialized services in 2013/14 was £544 million, and the money spent on high-cost drugs was £156 million.

The committee acknowledged that the estimate of the incremental cost of eculizumab made by Alexion Pharmaceuticals (the company developing eculizumab) compared with standard care was considerable. And incremental costs estimated by the evidence review group were higher still (although results are confidential).

Alexion estimated that eculizumab produced 25.22 additional quality-adjusted life-years (QALYs) per patient compared with standard care. Although the QALYs estimated in the evidence review group’s analysis were markedly lower than those calculated by the company, the advisory committee said both analyses produced substantial QALY gains of a magnitude that is rarely seen for any new drug.

For more information, see the guidance on the NICE website.

Eculizumab (Solirus)

Credit: Globovision

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending eculizumab (Soliris) as a treatment for atypical hemolytic uremic syndrome (aHUS), but only if certain conditions are met.

The guidance is the first to be produced as part of NICE’s highly specialized technologies program to evaluate treatments for very rare conditions.

aHUS affects around 200 people in England, with 20 to 30 new patients diagnosed with the condition each year.

The condition causes inflammation of blood vessels and thrombus formation throughout the body. So aHUS patients are at constant risk of sudden and progressive damage to, and failure of, vital organs.

“aHUS is a very distressing condition that imposes a significant burden both on those with the condition and their carers and families,” said NICE Chief Executive Sir Andrew Dillon.

“[A committee advising NICE] accepted that eculizumab is a step change in the management of aHUS and can be considered a significant innovation for a disease with a high unmet clinical need. It offers people with aHUS the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”

“The drug is, however, very expensive. The committee felt that the budget impact of eculizumab would be lower if the potential for adjusting the dose of the drug and stopping treatment was explored. This is reflected in the guidance, which recommends eculizumab should be funded only if important conditions are met, including the development of rules for starting and stopping treatment for clinical reasons. In the meantime, NHS England and the company should consider what opportunities might exist to reduce the cost of eculizumab to the NHS.”

The conditions for funding eculizumab are as follows:

• Use of the drug must be coordinated through an expert center.
• Monitoring systems must record the number of people with aHUS, the number who receive eculizumab, and the dose and duration of treatment.
• A national protocol must be developed for starting and stopping eculizumab for clinical reasons.
• A research program is needed with robust methods to evaluate when stopping treatment or dose adjustment might occur.

Eculizumab usage and costs

Eculizumab is given intravenously in adults as initial treatment at a dose of 900 mg for 4 weeks, then as maintenance treatment at a dose of 1200 mg on week 5 and then every 12 to 16 days.

The summary of product characteristics for eculizumab states that “treatment is recommended to continue for a patient’s lifetime, unless discontinuation of treatment is clinically indicated.” Eculizumab costs £3150 per 30 mL vial (excluding tax).

The net budget impact of eculizumab is confidential. However, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information that is available in the public domain.

This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult) and assumes a patient cohort of 170, as estimated by NHS England.

If it is assumed that all of these adults with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.

If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2, assuming all new patients are treated and all existing patients continue to be treated at the maintenance cost of £327,600 per year.

Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).

NHS England has indicated that the amount of the budget allocated for highly specialized services in 2013/14 was £544 million, and the money spent on high-cost drugs was £156 million.

The committee acknowledged that the estimate of the incremental cost of eculizumab made by Alexion Pharmaceuticals (the company developing eculizumab) compared with standard care was considerable. And incremental costs estimated by the evidence review group were higher still (although results are confidential).

Alexion estimated that eculizumab produced 25.22 additional quality-adjusted life-years (QALYs) per patient compared with standard care. Although the QALYs estimated in the evidence review group’s analysis were markedly lower than those calculated by the company, the advisory committee said both analyses produced substantial QALY gains of a magnitude that is rarely seen for any new drug.

For more information, see the guidance on the NICE website.

LAKE BUENA VISTA, FLA. – Regionalized trauma care significantly reduces long-term mortality and maintains similar functional outcomes in patients with severe traumatic brain injury, a study showed.

Regionalization of trauma care is a health care strategy that attempts to improve outcomes for trauma patients by setting up a tiered, integrated system that aims to match the injured patient with the appropriate health care facility in a timely fashion. The Northern Ohio Trauma System (NOTS) was created in 2010 to manage trauma patients using the regionalization model.

In this study of outcomes in NOTS patients, longer-term follow-up of 3,496 severe traumatic brain injury (TBI) admissions showed 30-day mortality fell from 21% to 16% after regionalization (24% relative reduction; P value < .0001) and 6-month mortality declined from 24% to 20% (17% relative reduction; P = .004).

Multivariable logistic regression only strengthened the effect of regionalization on the primary outcome, lead study author Dr. Michael Kelly said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma (EAST).

The odds ratio for 30-day mortality was 0.74, representing a 26% relative mortality reduction, and 0.82 for 6-month mortality, representing an 18% relative reduction.

At last year’s EAST meeting, Dr. Kelly and his colleagues reported that hospital mortality declined from 19% (262/1,359 patients) to 14% (302/2,137) in patients with severe TBI after the creation of the NOTS in 2010.

Despite bucking the current trend of rising mortality in hospitalized TBI patients, particularly those with severe brain injuries, their previous results were criticized by some as incomplete because hospital mortality was used without functional status measures or long-term mortality, he said.

To bridge the knowledge gap, the investigators identified all TBI patients older than 14 years with a Head Abbreviated Injury Scale (AIS) ≥ 3 from 2008 to 2012 in the NOTS database and matched them to the Ohio death index and the regional TBI rehabilitation database. Overall Functional Independence Measure (FIM) scores and FIM score gains were compared in 414 patients who were discharged to the regional TBI rehabilitation unit.

As a general rule of thumb, an overall FIM score of 60 is equivalent to 4 hours of personal care assistance in a nursing facility–type setting, a score of 80 equals 2 hours of personalized care in a nursing facility, more than 80 means the patient is able to receive family care at home, and ≥ 100 means minimal burdens in personal care, said Dr. Kelly of the MetroHealth Medical Center, Cleveland, and Cleveland Clinic.

A gain of 22 points is considered a minimal clinically important difference (MCID) for the overall FIM score. The MCID is 17 points for a FIM motor subscale gain, 3 for a FIM cognitive subscale gain, and has not been established for the FIM social subscale.

Overall FIM scores were similar before and after regionalization of trauma care (RT) at admission (54 vs. 48; P = .2) and at discharge (92 vs. 89; P = .1), he said.

FIM scores were similar in both groups at admission and discharge on the cognitive and social subscale domains, but were significantly lower post RT on the motor subscale at admission (38 vs. 31; P = .02) and discharge (68 vs. 65; P = .03). These differences were not clinically significant, according to Dr. Kelly and senior study author Dr. Jeffrey Claridge, NOTS medical director.

Pre- and post-RT patients had similar overall FIM score gains (37 vs. 36; P = .6), motor subscale gains (both groups 29), and social subscale gains (both groups 1). FIM cognitive subscale gains were significantly lower post RT (6 vs. 5; P = .01), but this difference was also not clinically significant.

Notably, discharges to regional TBI rehabilitation increased from 9% before RT to 14% after RT, Dr. Kelly said. The percentage of patients who were discharged to a skilled nurse facility or long-term care facility remained stable at about 30%, as did the percentage discharged home at about 40%.

“Regionalization improves long-term survival and maintains similar functional outcomes for patients with severe traumatic brain injury,” he concluded.

Patrice Wendling/Frontline Medical News

Discussant Dr. Jeffrey Coughenour of the University of Missouri Health System in Columbia said it appears regionalization is working, but added, “While we are saving more lives, what kind of lives are we saving? A question that has ever increasing implications for patients and payers evaluating the care we provide.”

He praised the investigators for using the FIM scale rather than the Glasgow Outcome Scale to try and answer this question, but said more information is needed on whether FIM scores improved in more challenging patients such as those with an AIS score of 4 or 5 or those entering rehabilitation after discharge to a skilled nursing or long-term care facility.

Data were not broken down for these more challenging subsets, Dr. Kelly said. The question of quality of life post regionalization was asked after the first study and that functional status was shown to be maintained in TBI patients in the follow-up study.

“Since no major changes in the hospital-based care or rehabilitation care of these TBI patients occurred, we weren’t surprised to see that functional outcomes did not improve,” he said in an interview. “The regionalization protocols were designed primarily to improve survival.”

During a discussion of the results, audience members questioned whether the investigators could be certain the results could be attributed to regionalization and not improvements in treatment of concurrent injuries or improvements in TBI treatment already underway at the time of policy change.

For the most part, these patients had isolated TBIs and no major changes in personnel or TBI care occurred during the study period, Dr. Kelly said.

Under NOTS, region-wide initiatives included use of the Centers for Disease Control and Prevention guidelines for field triage, a transfer line and transfer protocols, and a research database shared between two large hospital systems comprising the level I MetroHealth Medical Center trauma center, two level II trauma centers, and 12 nontrauma hospitals.

Dr. Kelly, his coauthors, and Dr. Coughenour reported no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Regionalized trauma care significantly reduces long-term mortality and maintains similar functional outcomes in patients with severe traumatic brain injury, a study showed.

Regionalization of trauma care is a health care strategy that attempts to improve outcomes for trauma patients by setting up a tiered, integrated system that aims to match the injured patient with the appropriate health care facility in a timely fashion. The Northern Ohio Trauma System (NOTS) was created in 2010 to manage trauma patients using the regionalization model.

In this study of outcomes in NOTS patients, longer-term follow-up of 3,496 severe traumatic brain injury (TBI) admissions showed 30-day mortality fell from 21% to 16% after regionalization (24% relative reduction; P value < .0001) and 6-month mortality declined from 24% to 20% (17% relative reduction; P = .004).

Multivariable logistic regression only strengthened the effect of regionalization on the primary outcome, lead study author Dr. Michael Kelly said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma (EAST).

The odds ratio for 30-day mortality was 0.74, representing a 26% relative mortality reduction, and 0.82 for 6-month mortality, representing an 18% relative reduction.

At last year’s EAST meeting, Dr. Kelly and his colleagues reported that hospital mortality declined from 19% (262/1,359 patients) to 14% (302/2,137) in patients with severe TBI after the creation of the NOTS in 2010.

Despite bucking the current trend of rising mortality in hospitalized TBI patients, particularly those with severe brain injuries, their previous results were criticized by some as incomplete because hospital mortality was used without functional status measures or long-term mortality, he said.

To bridge the knowledge gap, the investigators identified all TBI patients older than 14 years with a Head Abbreviated Injury Scale (AIS) ≥ 3 from 2008 to 2012 in the NOTS database and matched them to the Ohio death index and the regional TBI rehabilitation database. Overall Functional Independence Measure (FIM) scores and FIM score gains were compared in 414 patients who were discharged to the regional TBI rehabilitation unit.

As a general rule of thumb, an overall FIM score of 60 is equivalent to 4 hours of personal care assistance in a nursing facility–type setting, a score of 80 equals 2 hours of personalized care in a nursing facility, more than 80 means the patient is able to receive family care at home, and ≥ 100 means minimal burdens in personal care, said Dr. Kelly of the MetroHealth Medical Center, Cleveland, and Cleveland Clinic.

A gain of 22 points is considered a minimal clinically important difference (MCID) for the overall FIM score. The MCID is 17 points for a FIM motor subscale gain, 3 for a FIM cognitive subscale gain, and has not been established for the FIM social subscale.

Overall FIM scores were similar before and after regionalization of trauma care (RT) at admission (54 vs. 48; P = .2) and at discharge (92 vs. 89; P = .1), he said.

FIM scores were similar in both groups at admission and discharge on the cognitive and social subscale domains, but were significantly lower post RT on the motor subscale at admission (38 vs. 31; P = .02) and discharge (68 vs. 65; P = .03). These differences were not clinically significant, according to Dr. Kelly and senior study author Dr. Jeffrey Claridge, NOTS medical director.

Pre- and post-RT patients had similar overall FIM score gains (37 vs. 36; P = .6), motor subscale gains (both groups 29), and social subscale gains (both groups 1). FIM cognitive subscale gains were significantly lower post RT (6 vs. 5; P = .01), but this difference was also not clinically significant.

Notably, discharges to regional TBI rehabilitation increased from 9% before RT to 14% after RT, Dr. Kelly said. The percentage of patients who were discharged to a skilled nurse facility or long-term care facility remained stable at about 30%, as did the percentage discharged home at about 40%.

“Regionalization improves long-term survival and maintains similar functional outcomes for patients with severe traumatic brain injury,” he concluded.

Patrice Wendling/Frontline Medical News

Discussant Dr. Jeffrey Coughenour of the University of Missouri Health System in Columbia said it appears regionalization is working, but added, “While we are saving more lives, what kind of lives are we saving? A question that has ever increasing implications for patients and payers evaluating the care we provide.”

He praised the investigators for using the FIM scale rather than the Glasgow Outcome Scale to try and answer this question, but said more information is needed on whether FIM scores improved in more challenging patients such as those with an AIS score of 4 or 5 or those entering rehabilitation after discharge to a skilled nursing or long-term care facility.

Data were not broken down for these more challenging subsets, Dr. Kelly said. The question of quality of life post regionalization was asked after the first study and that functional status was shown to be maintained in TBI patients in the follow-up study.

“Since no major changes in the hospital-based care or rehabilitation care of these TBI patients occurred, we weren’t surprised to see that functional outcomes did not improve,” he said in an interview. “The regionalization protocols were designed primarily to improve survival.”

During a discussion of the results, audience members questioned whether the investigators could be certain the results could be attributed to regionalization and not improvements in treatment of concurrent injuries or improvements in TBI treatment already underway at the time of policy change.

For the most part, these patients had isolated TBIs and no major changes in personnel or TBI care occurred during the study period, Dr. Kelly said.

Under NOTS, region-wide initiatives included use of the Centers for Disease Control and Prevention guidelines for field triage, a transfer line and transfer protocols, and a research database shared between two large hospital systems comprising the level I MetroHealth Medical Center trauma center, two level II trauma centers, and 12 nontrauma hospitals.

Dr. Kelly, his coauthors, and Dr. Coughenour reported no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Regionalized trauma care significantly reduces long-term mortality and maintains similar functional outcomes in patients with severe traumatic brain injury, a study showed.

Regionalization of trauma care is a health care strategy that attempts to improve outcomes for trauma patients by setting up a tiered, integrated system that aims to match the injured patient with the appropriate health care facility in a timely fashion. The Northern Ohio Trauma System (NOTS) was created in 2010 to manage trauma patients using the regionalization model.

In this study of outcomes in NOTS patients, longer-term follow-up of 3,496 severe traumatic brain injury (TBI) admissions showed 30-day mortality fell from 21% to 16% after regionalization (24% relative reduction; P value < .0001) and 6-month mortality declined from 24% to 20% (17% relative reduction; P = .004).

Multivariable logistic regression only strengthened the effect of regionalization on the primary outcome, lead study author Dr. Michael Kelly said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma (EAST).

The odds ratio for 30-day mortality was 0.74, representing a 26% relative mortality reduction, and 0.82 for 6-month mortality, representing an 18% relative reduction.

At last year’s EAST meeting, Dr. Kelly and his colleagues reported that hospital mortality declined from 19% (262/1,359 patients) to 14% (302/2,137) in patients with severe TBI after the creation of the NOTS in 2010.

Despite bucking the current trend of rising mortality in hospitalized TBI patients, particularly those with severe brain injuries, their previous results were criticized by some as incomplete because hospital mortality was used without functional status measures or long-term mortality, he said.

To bridge the knowledge gap, the investigators identified all TBI patients older than 14 years with a Head Abbreviated Injury Scale (AIS) ≥ 3 from 2008 to 2012 in the NOTS database and matched them to the Ohio death index and the regional TBI rehabilitation database. Overall Functional Independence Measure (FIM) scores and FIM score gains were compared in 414 patients who were discharged to the regional TBI rehabilitation unit.

As a general rule of thumb, an overall FIM score of 60 is equivalent to 4 hours of personal care assistance in a nursing facility–type setting, a score of 80 equals 2 hours of personalized care in a nursing facility, more than 80 means the patient is able to receive family care at home, and ≥ 100 means minimal burdens in personal care, said Dr. Kelly of the MetroHealth Medical Center, Cleveland, and Cleveland Clinic.

A gain of 22 points is considered a minimal clinically important difference (MCID) for the overall FIM score. The MCID is 17 points for a FIM motor subscale gain, 3 for a FIM cognitive subscale gain, and has not been established for the FIM social subscale.

Overall FIM scores were similar before and after regionalization of trauma care (RT) at admission (54 vs. 48; P = .2) and at discharge (92 vs. 89; P = .1), he said.

FIM scores were similar in both groups at admission and discharge on the cognitive and social subscale domains, but were significantly lower post RT on the motor subscale at admission (38 vs. 31; P = .02) and discharge (68 vs. 65; P = .03). These differences were not clinically significant, according to Dr. Kelly and senior study author Dr. Jeffrey Claridge, NOTS medical director.

Pre- and post-RT patients had similar overall FIM score gains (37 vs. 36; P = .6), motor subscale gains (both groups 29), and social subscale gains (both groups 1). FIM cognitive subscale gains were significantly lower post RT (6 vs. 5; P = .01), but this difference was also not clinically significant.

Notably, discharges to regional TBI rehabilitation increased from 9% before RT to 14% after RT, Dr. Kelly said. The percentage of patients who were discharged to a skilled nurse facility or long-term care facility remained stable at about 30%, as did the percentage discharged home at about 40%.

“Regionalization improves long-term survival and maintains similar functional outcomes for patients with severe traumatic brain injury,” he concluded.

Patrice Wendling/Frontline Medical News

Discussant Dr. Jeffrey Coughenour of the University of Missouri Health System in Columbia said it appears regionalization is working, but added, “While we are saving more lives, what kind of lives are we saving? A question that has ever increasing implications for patients and payers evaluating the care we provide.”

He praised the investigators for using the FIM scale rather than the Glasgow Outcome Scale to try and answer this question, but said more information is needed on whether FIM scores improved in more challenging patients such as those with an AIS score of 4 or 5 or those entering rehabilitation after discharge to a skilled nursing or long-term care facility.

Data were not broken down for these more challenging subsets, Dr. Kelly said. The question of quality of life post regionalization was asked after the first study and that functional status was shown to be maintained in TBI patients in the follow-up study.

“Since no major changes in the hospital-based care or rehabilitation care of these TBI patients occurred, we weren’t surprised to see that functional outcomes did not improve,” he said in an interview. “The regionalization protocols were designed primarily to improve survival.”

During a discussion of the results, audience members questioned whether the investigators could be certain the results could be attributed to regionalization and not improvements in treatment of concurrent injuries or improvements in TBI treatment already underway at the time of policy change.

For the most part, these patients had isolated TBIs and no major changes in personnel or TBI care occurred during the study period, Dr. Kelly said.

Under NOTS, region-wide initiatives included use of the Centers for Disease Control and Prevention guidelines for field triage, a transfer line and transfer protocols, and a research database shared between two large hospital systems comprising the level I MetroHealth Medical Center trauma center, two level II trauma centers, and 12 nontrauma hospitals.

Dr. Kelly, his coauthors, and Dr. Coughenour reported no financial disclosures.

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