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Efficacy of neurostimulation for epilepsy underestimated with patient reports
WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.
In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).
In this study, investigators evaluated seizure frequency in the first 2 months after RNS implantation with the ECoG component of the RNS device. They assessed change in seizure frequency relative to this baseline at 3, 6, and 12 months, and also compared the reduction in seizures against the patient self-report of baseline seizure activity.
The differences were large. On patient report, the reduction in seizure activity at month 3 was just 10%, compared with 85% when measured on ECoG.
“Our results with the RNS compare favorably to the pivotal trial only when using the ECoG seizure frequency baseline. The reason for this discrepancy is due to underreporting of seizures by patients and consequently a falsely low seizure frequency,” Dr. Young explained at the meeting.
The RNS system has been implanted for refractory focal or partial seizures in adult patients at UCI since 2015. The device is indicated for adjunctive use in patients not adequately controlled on at least two antiepileptic medications. Twelve patients have been treated, but two were excluded from this analysis because they had surgical resection at the time of the RNS implantation and one because of an infection related to the implantation.
In general, patients treated at UCI had characteristics similar to those in the pivotal trial, which was published more than 3 years ago (Epilepsia. 2014;55[3]:432-41). In that 191-patient trial, the reduction in seizure frequency at the end of 5 months of blinded analysis with RNS was 37.9% versus 17.3% for a sham procedure. Progressive further reductions in seizure activity were observed during an extended open-label follow-up.
In the UCI analysis, the mean reduction in seizure frequency at 12 months was 56% relative to the patient-reported baseline but 78% on the basis of the ECoG analysis. Although only four of the nine patients have 12 or more months of follow-up, three were considered to be responders to RNS whether evaluated in relation to the patient-reported baseline seizure activity or in relation to ECoG. The responder rate at 3 months on the basis of patient-reported baseline activity, however, was only 56%, compared with 100% based on ECoG.
“The big issue is underreporting of seizures by patients,” Dr. Young explained. He cited numerous other studies demonstrating the same phenomenon. He noted that noncompliance is only one reason patients underreport. In many cases, patients are simply unaware of seizure activity.
Based on these data, “we think ECoG may be a more objective way to track patient response to RNS,” Dr. Young said. He acknowledged that the number of patients limits this study and suggested that larger studies are needed to confirm the findings.
Dr. Young reported having no potential conflicts of interest related to this topic.
SOURCE: Young M et al. AES abstract 3.109.
WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.
In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).
In this study, investigators evaluated seizure frequency in the first 2 months after RNS implantation with the ECoG component of the RNS device. They assessed change in seizure frequency relative to this baseline at 3, 6, and 12 months, and also compared the reduction in seizures against the patient self-report of baseline seizure activity.
The differences were large. On patient report, the reduction in seizure activity at month 3 was just 10%, compared with 85% when measured on ECoG.
“Our results with the RNS compare favorably to the pivotal trial only when using the ECoG seizure frequency baseline. The reason for this discrepancy is due to underreporting of seizures by patients and consequently a falsely low seizure frequency,” Dr. Young explained at the meeting.
The RNS system has been implanted for refractory focal or partial seizures in adult patients at UCI since 2015. The device is indicated for adjunctive use in patients not adequately controlled on at least two antiepileptic medications. Twelve patients have been treated, but two were excluded from this analysis because they had surgical resection at the time of the RNS implantation and one because of an infection related to the implantation.
In general, patients treated at UCI had characteristics similar to those in the pivotal trial, which was published more than 3 years ago (Epilepsia. 2014;55[3]:432-41). In that 191-patient trial, the reduction in seizure frequency at the end of 5 months of blinded analysis with RNS was 37.9% versus 17.3% for a sham procedure. Progressive further reductions in seizure activity were observed during an extended open-label follow-up.
In the UCI analysis, the mean reduction in seizure frequency at 12 months was 56% relative to the patient-reported baseline but 78% on the basis of the ECoG analysis. Although only four of the nine patients have 12 or more months of follow-up, three were considered to be responders to RNS whether evaluated in relation to the patient-reported baseline seizure activity or in relation to ECoG. The responder rate at 3 months on the basis of patient-reported baseline activity, however, was only 56%, compared with 100% based on ECoG.
“The big issue is underreporting of seizures by patients,” Dr. Young explained. He cited numerous other studies demonstrating the same phenomenon. He noted that noncompliance is only one reason patients underreport. In many cases, patients are simply unaware of seizure activity.
Based on these data, “we think ECoG may be a more objective way to track patient response to RNS,” Dr. Young said. He acknowledged that the number of patients limits this study and suggested that larger studies are needed to confirm the findings.
Dr. Young reported having no potential conflicts of interest related to this topic.
SOURCE: Young M et al. AES abstract 3.109.
WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.
In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).
In this study, investigators evaluated seizure frequency in the first 2 months after RNS implantation with the ECoG component of the RNS device. They assessed change in seizure frequency relative to this baseline at 3, 6, and 12 months, and also compared the reduction in seizures against the patient self-report of baseline seizure activity.
The differences were large. On patient report, the reduction in seizure activity at month 3 was just 10%, compared with 85% when measured on ECoG.
“Our results with the RNS compare favorably to the pivotal trial only when using the ECoG seizure frequency baseline. The reason for this discrepancy is due to underreporting of seizures by patients and consequently a falsely low seizure frequency,” Dr. Young explained at the meeting.
The RNS system has been implanted for refractory focal or partial seizures in adult patients at UCI since 2015. The device is indicated for adjunctive use in patients not adequately controlled on at least two antiepileptic medications. Twelve patients have been treated, but two were excluded from this analysis because they had surgical resection at the time of the RNS implantation and one because of an infection related to the implantation.
In general, patients treated at UCI had characteristics similar to those in the pivotal trial, which was published more than 3 years ago (Epilepsia. 2014;55[3]:432-41). In that 191-patient trial, the reduction in seizure frequency at the end of 5 months of blinded analysis with RNS was 37.9% versus 17.3% for a sham procedure. Progressive further reductions in seizure activity were observed during an extended open-label follow-up.
In the UCI analysis, the mean reduction in seizure frequency at 12 months was 56% relative to the patient-reported baseline but 78% on the basis of the ECoG analysis. Although only four of the nine patients have 12 or more months of follow-up, three were considered to be responders to RNS whether evaluated in relation to the patient-reported baseline seizure activity or in relation to ECoG. The responder rate at 3 months on the basis of patient-reported baseline activity, however, was only 56%, compared with 100% based on ECoG.
“The big issue is underreporting of seizures by patients,” Dr. Young explained. He cited numerous other studies demonstrating the same phenomenon. He noted that noncompliance is only one reason patients underreport. In many cases, patients are simply unaware of seizure activity.
Based on these data, “we think ECoG may be a more objective way to track patient response to RNS,” Dr. Young said. He acknowledged that the number of patients limits this study and suggested that larger studies are needed to confirm the findings.
Dr. Young reported having no potential conflicts of interest related to this topic.
SOURCE: Young M et al. AES abstract 3.109.
REPORTING FROM AES 2017
Key clinical point:
Major finding: At 3 months after implantation, seizure activity was reduced 10% by patient report but 85% by objective measurement.
Data source: Retrospective study of nine patients implanted with the Responsive Neurostimulation System.
Disclosures: Dr. Young reported having no potential conflicts of interest related to this topic.
Source: Young M et al. AES abstract 3.109.
Toy stethoscopes
Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.
In medical school, I was taught that the most important part of a stethoscope is between the ears. I believe that statement is true, but in a similar way to how I choose wines. My palate can’t tell the difference between a $15 and a $50 bottle of wine, so buying more expensive wine is a waste. However, a $3 bottle of wine is clearly inferior, if not undrinkable. There are oenophiles (one a distant cousin in Norway) who have trained their palates to tell the difference in wines, just as there are audiophiles who support the sales of $1,000 stereo speakers. Some fraction of those snobs may have justification. So, if cardiologists have strong opinions on stethoscopes, I won’t begrudge them their choice of a more expensive model. Their tastes do not mean that the average person should spend that much on wine, speakers, or stethoscopes. I will assert that there was a time when I could tell a day or two in advance that my otoscope bulb was going to burn out. The color balance was wrong. I carried a pocket otoscope for a few years when rounding in the hospital, but never found it as accurate as my original one. Every craftsman gets accustomed to their best tools.
A professional should be aware of the minimum quality of tool needed to get the job done.
Toy isolation stethoscopes ($3 each retail in bulk) add nothing to my discernment of an infant with bronchiolitis who is distressed, so I consider that equipment a waste of money and polluting to the environment. I typically use my stethoscope and foam it on leaving the room. There is evidence that either foam or alcohol pads are effective1 in killing germs, but no proof that this hygiene makes a difference clinically.2 The myriad researchers who have published about stethoscope contamination have stopped at padding their academic portfolios with something easy to publish, which basically is a high school science project using agar plates. They then make insinuations about policy, without any cost-benefit analysis. They really haven’t been bothered enough to advance the science of clinical medicine and actually measure a clinical impact of these policies. It is a corruption of science created by the publish-or-perish environment.
One survey found that 45% of physicians disinfect their stethoscope annually or less. Laundering of white coats follows a similar pattern, which is why the British National Health Service banned lab coats for physicians 10 years ago. No ties or long sleeve shirts either. I am smug knowing that my sartorial sense was ahead of my time in this regard.
The quality-improvement work of Ignaz Semmelweis should be required reading for all physicians. The control chart3 he published on puerperal fever in Vienna in the 1840s is spectacular. Infection control is important. Modern medical science cannot produce a similar control chart to justify the amount of dollars spent annually on gowns, gloves, masks, and toy stethoscopes. Sad.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. Am J Infect Control. 2009 Apr;37(3):241-3.
2. J Hosp Infect. 2015 Sep;91(1):1-7.
3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever
Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.
In medical school, I was taught that the most important part of a stethoscope is between the ears. I believe that statement is true, but in a similar way to how I choose wines. My palate can’t tell the difference between a $15 and a $50 bottle of wine, so buying more expensive wine is a waste. However, a $3 bottle of wine is clearly inferior, if not undrinkable. There are oenophiles (one a distant cousin in Norway) who have trained their palates to tell the difference in wines, just as there are audiophiles who support the sales of $1,000 stereo speakers. Some fraction of those snobs may have justification. So, if cardiologists have strong opinions on stethoscopes, I won’t begrudge them their choice of a more expensive model. Their tastes do not mean that the average person should spend that much on wine, speakers, or stethoscopes. I will assert that there was a time when I could tell a day or two in advance that my otoscope bulb was going to burn out. The color balance was wrong. I carried a pocket otoscope for a few years when rounding in the hospital, but never found it as accurate as my original one. Every craftsman gets accustomed to their best tools.
A professional should be aware of the minimum quality of tool needed to get the job done.
Toy isolation stethoscopes ($3 each retail in bulk) add nothing to my discernment of an infant with bronchiolitis who is distressed, so I consider that equipment a waste of money and polluting to the environment. I typically use my stethoscope and foam it on leaving the room. There is evidence that either foam or alcohol pads are effective1 in killing germs, but no proof that this hygiene makes a difference clinically.2 The myriad researchers who have published about stethoscope contamination have stopped at padding their academic portfolios with something easy to publish, which basically is a high school science project using agar plates. They then make insinuations about policy, without any cost-benefit analysis. They really haven’t been bothered enough to advance the science of clinical medicine and actually measure a clinical impact of these policies. It is a corruption of science created by the publish-or-perish environment.
One survey found that 45% of physicians disinfect their stethoscope annually or less. Laundering of white coats follows a similar pattern, which is why the British National Health Service banned lab coats for physicians 10 years ago. No ties or long sleeve shirts either. I am smug knowing that my sartorial sense was ahead of my time in this regard.
The quality-improvement work of Ignaz Semmelweis should be required reading for all physicians. The control chart3 he published on puerperal fever in Vienna in the 1840s is spectacular. Infection control is important. Modern medical science cannot produce a similar control chart to justify the amount of dollars spent annually on gowns, gloves, masks, and toy stethoscopes. Sad.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. Am J Infect Control. 2009 Apr;37(3):241-3.
2. J Hosp Infect. 2015 Sep;91(1):1-7.
3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever
Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.
In medical school, I was taught that the most important part of a stethoscope is between the ears. I believe that statement is true, but in a similar way to how I choose wines. My palate can’t tell the difference between a $15 and a $50 bottle of wine, so buying more expensive wine is a waste. However, a $3 bottle of wine is clearly inferior, if not undrinkable. There are oenophiles (one a distant cousin in Norway) who have trained their palates to tell the difference in wines, just as there are audiophiles who support the sales of $1,000 stereo speakers. Some fraction of those snobs may have justification. So, if cardiologists have strong opinions on stethoscopes, I won’t begrudge them their choice of a more expensive model. Their tastes do not mean that the average person should spend that much on wine, speakers, or stethoscopes. I will assert that there was a time when I could tell a day or two in advance that my otoscope bulb was going to burn out. The color balance was wrong. I carried a pocket otoscope for a few years when rounding in the hospital, but never found it as accurate as my original one. Every craftsman gets accustomed to their best tools.
A professional should be aware of the minimum quality of tool needed to get the job done.
Toy isolation stethoscopes ($3 each retail in bulk) add nothing to my discernment of an infant with bronchiolitis who is distressed, so I consider that equipment a waste of money and polluting to the environment. I typically use my stethoscope and foam it on leaving the room. There is evidence that either foam or alcohol pads are effective1 in killing germs, but no proof that this hygiene makes a difference clinically.2 The myriad researchers who have published about stethoscope contamination have stopped at padding their academic portfolios with something easy to publish, which basically is a high school science project using agar plates. They then make insinuations about policy, without any cost-benefit analysis. They really haven’t been bothered enough to advance the science of clinical medicine and actually measure a clinical impact of these policies. It is a corruption of science created by the publish-or-perish environment.
One survey found that 45% of physicians disinfect their stethoscope annually or less. Laundering of white coats follows a similar pattern, which is why the British National Health Service banned lab coats for physicians 10 years ago. No ties or long sleeve shirts either. I am smug knowing that my sartorial sense was ahead of my time in this regard.
The quality-improvement work of Ignaz Semmelweis should be required reading for all physicians. The control chart3 he published on puerperal fever in Vienna in the 1840s is spectacular. Infection control is important. Modern medical science cannot produce a similar control chart to justify the amount of dollars spent annually on gowns, gloves, masks, and toy stethoscopes. Sad.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. Am J Infect Control. 2009 Apr;37(3):241-3.
2. J Hosp Infect. 2015 Sep;91(1):1-7.
3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever
Many Vets Lack Easy Access to Healthy Food Outlets
The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.
The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.
Related: Food Insecurity Among Veterans
In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.
The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.
Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?
Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”
The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.
The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.
Related: Food Insecurity Among Veterans
In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.
The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.
Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?
Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”
The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.
The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.
Related: Food Insecurity Among Veterans
In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.
The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.
Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?
Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”
Edoxaban noninferior to dalteparin for VTE in cancer
ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.
In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.
Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.
Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).
Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.
Patients and treatment
Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.
Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.
Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.
Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.
The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.
Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.
Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.
About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.
About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.
Results
The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.
This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).
“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”
The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).
The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).
“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”
Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).
The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).
“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.” 
ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.
In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.
Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.
Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).
Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.
Patients and treatment
Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.
Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.
Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.
Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.
The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.
Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.
Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.
About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.
About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.
Results
The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.
This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).
“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”
The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).
The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).
“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”
Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).
The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).
“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.”
ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.
In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.
Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.
Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).
Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.
Patients and treatment
Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.
Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.
Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.
Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.
The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.
Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.
Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.
About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.
About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.
Results
The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.
This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).
“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”
The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).
The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).
“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”
Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).
The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).
“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.”
FDA lifts clinical hold on fitusiran trials
The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.
The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.
Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.
The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.
The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.
As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.
Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.
With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.
“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.
“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”
About fitusiran
Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.
Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.
Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.
The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.
The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.
The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.
The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.
In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.
The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.
The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.
Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.
The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.
The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.
As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.
Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.
With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.
“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.
“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”
About fitusiran
Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.
Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.
Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.
The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.
The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.
The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.
The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.
In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.
The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.
The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.
Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.
The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.
The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.
As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.
Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.
With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.
“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.
“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”
About fitusiran
Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.
Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.
Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.
The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.
The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.
The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.
The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.
In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.
NK cell product receives orphan designation
The European Commission has granted orphan designation to a natural killer (NK) cell product for the treatment of multiple myeloma.
The product, called CellProtect, is manufactured from a patient’s own blood.
It consists of NK cells that have been activated and expanded so they can recognize and attack cancer cells.
CellProtect has been studied in a phase 1/2 trial of patients with multiple myeloma.
In this trial, the NK cell product was used as a supplement to autologous stem cell transplant.
CellProtect exhibited a good safety profile and signals of effect in the trial, according to CellProtect Nordic Pharmaceuticals AB, the company developing CellProtect.
Results from the trial are expected to be published in 2018.
“The decision from the commission is based on a recommendation from the European Medicines Agency’s Committee for Orphan Medicinal Products and confirms that a future product is considered to be of significant benefit to those suffering from multiple myeloma,” said Karin Mellström, chief executive officer of CellProtect Nordic Pharmaceuticals AB.
“We can now proceed and plan for additional clinical trials in order to receive approval to market CellProtect.”
Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Medicines Agency’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
The European Commission has granted orphan designation to a natural killer (NK) cell product for the treatment of multiple myeloma.
The product, called CellProtect, is manufactured from a patient’s own blood.
It consists of NK cells that have been activated and expanded so they can recognize and attack cancer cells.
CellProtect has been studied in a phase 1/2 trial of patients with multiple myeloma.
In this trial, the NK cell product was used as a supplement to autologous stem cell transplant.
CellProtect exhibited a good safety profile and signals of effect in the trial, according to CellProtect Nordic Pharmaceuticals AB, the company developing CellProtect.
Results from the trial are expected to be published in 2018.
“The decision from the commission is based on a recommendation from the European Medicines Agency’s Committee for Orphan Medicinal Products and confirms that a future product is considered to be of significant benefit to those suffering from multiple myeloma,” said Karin Mellström, chief executive officer of CellProtect Nordic Pharmaceuticals AB.
“We can now proceed and plan for additional clinical trials in order to receive approval to market CellProtect.”
Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Medicines Agency’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
The European Commission has granted orphan designation to a natural killer (NK) cell product for the treatment of multiple myeloma.
The product, called CellProtect, is manufactured from a patient’s own blood.
It consists of NK cells that have been activated and expanded so they can recognize and attack cancer cells.
CellProtect has been studied in a phase 1/2 trial of patients with multiple myeloma.
In this trial, the NK cell product was used as a supplement to autologous stem cell transplant.
CellProtect exhibited a good safety profile and signals of effect in the trial, according to CellProtect Nordic Pharmaceuticals AB, the company developing CellProtect.
Results from the trial are expected to be published in 2018.
“The decision from the commission is based on a recommendation from the European Medicines Agency’s Committee for Orphan Medicinal Products and confirms that a future product is considered to be of significant benefit to those suffering from multiple myeloma,” said Karin Mellström, chief executive officer of CellProtect Nordic Pharmaceuticals AB.
“We can now proceed and plan for additional clinical trials in order to receive approval to market CellProtect.”
Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Medicines Agency’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
FDA approves topical antibiotic for impetigo infections
The Food and Drug Administration has approved in patients aged 2 months or older.
This is the first topical treatment for impetigo to be approved in more than 10 years, according to the press release from the manufacturer, Medimetriks Pharmaceuticals.
Ozenoxacin is a quinolone antimicrobial. The prescribing information is available on the FDA website.
The Food and Drug Administration has approved in patients aged 2 months or older.
This is the first topical treatment for impetigo to be approved in more than 10 years, according to the press release from the manufacturer, Medimetriks Pharmaceuticals.
Ozenoxacin is a quinolone antimicrobial. The prescribing information is available on the FDA website.
The Food and Drug Administration has approved in patients aged 2 months or older.
This is the first topical treatment for impetigo to be approved in more than 10 years, according to the press release from the manufacturer, Medimetriks Pharmaceuticals.
Ozenoxacin is a quinolone antimicrobial. The prescribing information is available on the FDA website.
Juvéderm Voluma for Cheek Rejuvenation
Rare neurological complication linked to Waldenstrom disease
Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.
The patient, who had longstanding painful neuropathy, had presented to urgent care with a new-onset left facial nerve palsy, was then diagnosed with left Bell’s palsy, and began treatment with valacyclovir and prednisone.
The left-sided facial weakness gradually progressed to total paralysis of the left lower face and inability to close the left eye, and 2 weeks later, he developed right facial weakness that ran a similar course. The patient had a complicated clinical course that included symptomatic acute-on-chronic subdural hematoma, among other complications; eventually the patient’s symptoms stabilized and cranial neuropathies gradually improved, according to the report.
Bilateral facial nerve palsy is an extremely rare condition, occurring in just 0.3%-2% of all facial nerve palsy cases, according to the authors. By contrast, unilateral facial nerve palsy (or Bell’s palsy) is far more common, but it still occurs in only 25 patients per 100,000 population, they said.
Most cases of bilateral facial nerve palsy are caused by underlying Guillain-Barré syndrome, though some are congenital, related to trauma, or caused by etiologies that are metabolic, immunologic, or neoplastic in nature. While various types of neurological disturbances – from ischemic and hemorrhagic events to meningoencephalitis – have been documented to occur in up to a quarter of patients with Waldenstrom disease.
“Given the large differential that comprises the assessment of a bilateral facial nerve palsy, it warrants for an extensive work-up, and Waldenstrom’s macroglobulinemia should be sought as an additional possible etiology,” the authors wrote.
Dr. Torrealba-Acosta and coauthors reported having no financial disclosures.
SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.
Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.
The patient, who had longstanding painful neuropathy, had presented to urgent care with a new-onset left facial nerve palsy, was then diagnosed with left Bell’s palsy, and began treatment with valacyclovir and prednisone.
The left-sided facial weakness gradually progressed to total paralysis of the left lower face and inability to close the left eye, and 2 weeks later, he developed right facial weakness that ran a similar course. The patient had a complicated clinical course that included symptomatic acute-on-chronic subdural hematoma, among other complications; eventually the patient’s symptoms stabilized and cranial neuropathies gradually improved, according to the report.
Bilateral facial nerve palsy is an extremely rare condition, occurring in just 0.3%-2% of all facial nerve palsy cases, according to the authors. By contrast, unilateral facial nerve palsy (or Bell’s palsy) is far more common, but it still occurs in only 25 patients per 100,000 population, they said.
Most cases of bilateral facial nerve palsy are caused by underlying Guillain-Barré syndrome, though some are congenital, related to trauma, or caused by etiologies that are metabolic, immunologic, or neoplastic in nature. While various types of neurological disturbances – from ischemic and hemorrhagic events to meningoencephalitis – have been documented to occur in up to a quarter of patients with Waldenstrom disease.
“Given the large differential that comprises the assessment of a bilateral facial nerve palsy, it warrants for an extensive work-up, and Waldenstrom’s macroglobulinemia should be sought as an additional possible etiology,” the authors wrote.
Dr. Torrealba-Acosta and coauthors reported having no financial disclosures.
SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.
Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.
The patient, who had longstanding painful neuropathy, had presented to urgent care with a new-onset left facial nerve palsy, was then diagnosed with left Bell’s palsy, and began treatment with valacyclovir and prednisone.
The left-sided facial weakness gradually progressed to total paralysis of the left lower face and inability to close the left eye, and 2 weeks later, he developed right facial weakness that ran a similar course. The patient had a complicated clinical course that included symptomatic acute-on-chronic subdural hematoma, among other complications; eventually the patient’s symptoms stabilized and cranial neuropathies gradually improved, according to the report.
Bilateral facial nerve palsy is an extremely rare condition, occurring in just 0.3%-2% of all facial nerve palsy cases, according to the authors. By contrast, unilateral facial nerve palsy (or Bell’s palsy) is far more common, but it still occurs in only 25 patients per 100,000 population, they said.
Most cases of bilateral facial nerve palsy are caused by underlying Guillain-Barré syndrome, though some are congenital, related to trauma, or caused by etiologies that are metabolic, immunologic, or neoplastic in nature. While various types of neurological disturbances – from ischemic and hemorrhagic events to meningoencephalitis – have been documented to occur in up to a quarter of patients with Waldenstrom disease.
“Given the large differential that comprises the assessment of a bilateral facial nerve palsy, it warrants for an extensive work-up, and Waldenstrom’s macroglobulinemia should be sought as an additional possible etiology,” the authors wrote.
Dr. Torrealba-Acosta and coauthors reported having no financial disclosures.
SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.
FROM THE JOURNAL OF CLINICAL NEUROSCIENCE