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Congenital melanocytic nevi in the very young tend to be benign
Histopathology findings of cytologic atypia, architectural disorder, and pagetoid spread are common in congenital melanocytic nevi (CMN) of all sizes in children aged 0-35 months, and tend to have benign outcomes, according to a retrospective study.
Emily A. Simons, MPH, and her associates at Boston Children’s Hospital studied 197 nevi in 179 patients with an average age of 14 months (range, 4 days to 35 months); 51% were female. Of those, 80% had skin types I-II, and 90% were white. The majority of the lesions involved the head or trunk and were predominantly medium in size, and 58% had a projected adult size of 1.5-10 cm. The study was retrospective; cases had been diagnosed between 1993 and 2013.
Cytologic atypia, architectural disorder, and pagetoid spread were the most frequent features – they were present in 73% of nevi and were closely associated. Combined histologic patterns of a blue nevus, spindle and Spitz nevus, or a deep penetrating nevus were identified in 40% of CMN. Proliferative nodules occurred in 5% of nevi.
Clinical outcomes were available for 130 patients, including 26 with large CMN and 8 with proliferative nodules. The children were alive and had not been diagnosed with melanoma at a mean follow-up of a mean of 8.4 years (range, 7 months to 21.3 years), even though margins of the last excision were positive in 41% of all CMN and in 77% of large CMN.
Malignant transformation of CMN certainly should be recognized, but the morbidity of overdiagnosis also needs to be considered. “Excision of larger CMN might require serial excisions under general anesthesia, the use of tissue expanders, and grafts,” Dr. Simons and her associates said.
Among the limitations of this study were that the majority of patients were white, so the results may not translate to children with darker skin types, they noted.
“The diagnosis of malignant melanoma should be made with great caution in this population,” they concluded, pointing out that the histopathologic features alone (cytologic atypia, architectural disorder, and pagetoid spread) “should not be interpreted as evidence for potential malignant behavior or serve as grounds for further excision.”
Read more in the Journal of the American Academy of Dermatology (2017 May;76[5]941-7).
The authors had no relevant financial disorders.
Histopathology findings of cytologic atypia, architectural disorder, and pagetoid spread are common in congenital melanocytic nevi (CMN) of all sizes in children aged 0-35 months, and tend to have benign outcomes, according to a retrospective study.
Emily A. Simons, MPH, and her associates at Boston Children’s Hospital studied 197 nevi in 179 patients with an average age of 14 months (range, 4 days to 35 months); 51% were female. Of those, 80% had skin types I-II, and 90% were white. The majority of the lesions involved the head or trunk and were predominantly medium in size, and 58% had a projected adult size of 1.5-10 cm. The study was retrospective; cases had been diagnosed between 1993 and 2013.
Cytologic atypia, architectural disorder, and pagetoid spread were the most frequent features – they were present in 73% of nevi and were closely associated. Combined histologic patterns of a blue nevus, spindle and Spitz nevus, or a deep penetrating nevus were identified in 40% of CMN. Proliferative nodules occurred in 5% of nevi.
Clinical outcomes were available for 130 patients, including 26 with large CMN and 8 with proliferative nodules. The children were alive and had not been diagnosed with melanoma at a mean follow-up of a mean of 8.4 years (range, 7 months to 21.3 years), even though margins of the last excision were positive in 41% of all CMN and in 77% of large CMN.
Malignant transformation of CMN certainly should be recognized, but the morbidity of overdiagnosis also needs to be considered. “Excision of larger CMN might require serial excisions under general anesthesia, the use of tissue expanders, and grafts,” Dr. Simons and her associates said.
Among the limitations of this study were that the majority of patients were white, so the results may not translate to children with darker skin types, they noted.
“The diagnosis of malignant melanoma should be made with great caution in this population,” they concluded, pointing out that the histopathologic features alone (cytologic atypia, architectural disorder, and pagetoid spread) “should not be interpreted as evidence for potential malignant behavior or serve as grounds for further excision.”
Read more in the Journal of the American Academy of Dermatology (2017 May;76[5]941-7).
The authors had no relevant financial disorders.
Histopathology findings of cytologic atypia, architectural disorder, and pagetoid spread are common in congenital melanocytic nevi (CMN) of all sizes in children aged 0-35 months, and tend to have benign outcomes, according to a retrospective study.
Emily A. Simons, MPH, and her associates at Boston Children’s Hospital studied 197 nevi in 179 patients with an average age of 14 months (range, 4 days to 35 months); 51% were female. Of those, 80% had skin types I-II, and 90% were white. The majority of the lesions involved the head or trunk and were predominantly medium in size, and 58% had a projected adult size of 1.5-10 cm. The study was retrospective; cases had been diagnosed between 1993 and 2013.
Cytologic atypia, architectural disorder, and pagetoid spread were the most frequent features – they were present in 73% of nevi and were closely associated. Combined histologic patterns of a blue nevus, spindle and Spitz nevus, or a deep penetrating nevus were identified in 40% of CMN. Proliferative nodules occurred in 5% of nevi.
Clinical outcomes were available for 130 patients, including 26 with large CMN and 8 with proliferative nodules. The children were alive and had not been diagnosed with melanoma at a mean follow-up of a mean of 8.4 years (range, 7 months to 21.3 years), even though margins of the last excision were positive in 41% of all CMN and in 77% of large CMN.
Malignant transformation of CMN certainly should be recognized, but the morbidity of overdiagnosis also needs to be considered. “Excision of larger CMN might require serial excisions under general anesthesia, the use of tissue expanders, and grafts,” Dr. Simons and her associates said.
Among the limitations of this study were that the majority of patients were white, so the results may not translate to children with darker skin types, they noted.
“The diagnosis of malignant melanoma should be made with great caution in this population,” they concluded, pointing out that the histopathologic features alone (cytologic atypia, architectural disorder, and pagetoid spread) “should not be interpreted as evidence for potential malignant behavior or serve as grounds for further excision.”
Read more in the Journal of the American Academy of Dermatology (2017 May;76[5]941-7).
The authors had no relevant financial disorders.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
No Link Found Between Spike Frequency and Surgical Outcomes
An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.
Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.
An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.
Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.
An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.
Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.
Patients With Refractory Focal Epilepsy Have Older Brains
Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.
Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.
Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.
Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.
Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.
Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.
Infliximab safe for recently vaccinated Kawasaki patients
Infliximab is safe to use in infants and young children with Kawasaki disease (KD) who have recently received live viral vaccinations, reported Aaron M. Lee, MS, and his associates at Rady Children’s Hospital-San Diego.
The study included 38 children, aged either less than 18 months or 4-6 years, who received either a 5 mg/kg or a 10 mg/kg dose of infliximab within 90 days of receiving a live vaccination of MMR, varicella-zoster virus, or rotavirus. During a 90-day follow-up period, no serious infections requiring antimicrobial therapy or hospitalization were reported. A single patient who received an MMR/VZV vaccine 42 days before infliximab treatment developed urticaria 15 minutes after the infliximab transfusion began, which was resolved with hydroxyzine.
“The data presented here suggest that a single dose of infliximab can be safely administered to acute KD patients regardless of recent live virus vaccination,” the investigators concluded.
Find the full report in the Pediatric Infectious Disease Journal (2017 Apr;36(4):435-7).
Infliximab is safe to use in infants and young children with Kawasaki disease (KD) who have recently received live viral vaccinations, reported Aaron M. Lee, MS, and his associates at Rady Children’s Hospital-San Diego.
The study included 38 children, aged either less than 18 months or 4-6 years, who received either a 5 mg/kg or a 10 mg/kg dose of infliximab within 90 days of receiving a live vaccination of MMR, varicella-zoster virus, or rotavirus. During a 90-day follow-up period, no serious infections requiring antimicrobial therapy or hospitalization were reported. A single patient who received an MMR/VZV vaccine 42 days before infliximab treatment developed urticaria 15 minutes after the infliximab transfusion began, which was resolved with hydroxyzine.
“The data presented here suggest that a single dose of infliximab can be safely administered to acute KD patients regardless of recent live virus vaccination,” the investigators concluded.
Find the full report in the Pediatric Infectious Disease Journal (2017 Apr;36(4):435-7).
Infliximab is safe to use in infants and young children with Kawasaki disease (KD) who have recently received live viral vaccinations, reported Aaron M. Lee, MS, and his associates at Rady Children’s Hospital-San Diego.
The study included 38 children, aged either less than 18 months or 4-6 years, who received either a 5 mg/kg or a 10 mg/kg dose of infliximab within 90 days of receiving a live vaccination of MMR, varicella-zoster virus, or rotavirus. During a 90-day follow-up period, no serious infections requiring antimicrobial therapy or hospitalization were reported. A single patient who received an MMR/VZV vaccine 42 days before infliximab treatment developed urticaria 15 minutes after the infliximab transfusion began, which was resolved with hydroxyzine.
“The data presented here suggest that a single dose of infliximab can be safely administered to acute KD patients regardless of recent live virus vaccination,” the investigators concluded.
Find the full report in the Pediatric Infectious Disease Journal (2017 Apr;36(4):435-7).
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
The Risk of Seizures Following Stroke
About 5% of patients who have had an ischemic stroke develop seizures, according to an analysis of data from the Framingham Heart Study. When researchers looked at the incidence of strokes between 1982 and 2003 and followed patients for 20 years, they found strokes had occurred in 469 patients, 25 of whom had experienced a seizure (5.3%). A third of these seizures happened within the first 24 hours of the stroke onset; half occurred within 30 days.
Stefanidou M, Das RR, Beiser AS, et al. Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study. Seizure. 2017;47:105-110.
About 5% of patients who have had an ischemic stroke develop seizures, according to an analysis of data from the Framingham Heart Study. When researchers looked at the incidence of strokes between 1982 and 2003 and followed patients for 20 years, they found strokes had occurred in 469 patients, 25 of whom had experienced a seizure (5.3%). A third of these seizures happened within the first 24 hours of the stroke onset; half occurred within 30 days.
Stefanidou M, Das RR, Beiser AS, et al. Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study. Seizure. 2017;47:105-110.
About 5% of patients who have had an ischemic stroke develop seizures, according to an analysis of data from the Framingham Heart Study. When researchers looked at the incidence of strokes between 1982 and 2003 and followed patients for 20 years, they found strokes had occurred in 469 patients, 25 of whom had experienced a seizure (5.3%). A third of these seizures happened within the first 24 hours of the stroke onset; half occurred within 30 days.
Stefanidou M, Das RR, Beiser AS, et al. Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study. Seizure. 2017;47:105-110.
Clearer heads are a fuzzy subject
Those of you who were in high school or middle school in 1987, when the DSM II-R first included “Attention Deficit Disorder With and Without Hyperactivity” for the first time, missed out on the “discovery,” and subsequent commercialization, of a condition that had been percolating under physicians’ noses for hundreds of years.
You may have wondered what primary care physicians did with their time before they were inundated with requests for evaluations and medications to treat ADHD. You may not realize that we didn’t always have ADHD specialists to help us or several dozen stimulant concoctions from which to choose. In the beginning, ADHD specialists had to invent themselves while the pharmaceutical companies scrambled to meet the demand for drugs that were longer lasting and more palatable.
The increasing popularity of professional contact sports is probably what we have to thank for sharpening this focus on head injury. I suspect that, for the general population, there are no more concussions occurring today than there were 50 years ago. However, in the subgroup of professional and elite college athletes, the players’ increasing speed, size, and flagrant ignorance of the rules have resulted in more significant head injuries. When a highly paid megastar athlete must sit out key games, the management of his head injury generates a lot of attention and discussion.
I am sure that there also has been an increase in concussions among young women who now have more opportunities to participate in contact sports. However, I suspect that most of the apparent increase in the diagnosis among high school and younger athletes of both sexes is primarily the result of heightened awareness. I don’t know of data to support or refute this opinion.
I may be wrong about lack of a real increase in concussion injuries, but there can be no arguing about the explosion in the number of clinics and providers who advertise themselves as concussion specialists. Neurologists, psychologists, chiropractors, orthopedists, and sports medicine practitioners and trainers all have climbed on the bandwagon to satisfy the demand generated by this country’s new concussion awareness.
The problem is that, just as in the early days after the “discovery” of ADHD, the science behind much of the advice and management strategies for concussion just isn’t there. For example, resting the brain after a head injury sounds like a good idea. After all, it works for a torn hamstring. However, “sounds like” and “is” are two very different things.
In an excellent article in this publication (“Spotlight shifts to active treatment for concussions,” by Christine Kilgore), I found some comforting news that concussion management may be taking some baby steps into the realm of evidence-based decision management. The original results came from a pediatric population, but it now appears that prolonged rest, which is routinely recommended, can be counterproductive in many concussed patients. The physicians quoted in this article suggest that their experience is pointing to the need for active management in patients with a variety of postconcussion symptoms. Brian Hainline, MD, a clinical professor of neurology at New York University and Indiana University, Indianapolis, observes, “It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged.”
Of course, the science is still lagging behind and the observations by the physicians quoted in this article are based on small series, but their agreement deserves our attention. I urge you to take a look at this article to get an idea of where the management of concussion appears to be going. Not surprisingly, no two concussion patients are the same, and their management should be tailored to their needs. Reliance on overly simplistic guidelines not only doesn’t work but can do harm. It’s that old Hippocratic Oath thing again.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Those of you who were in high school or middle school in 1987, when the DSM II-R first included “Attention Deficit Disorder With and Without Hyperactivity” for the first time, missed out on the “discovery,” and subsequent commercialization, of a condition that had been percolating under physicians’ noses for hundreds of years.
You may have wondered what primary care physicians did with their time before they were inundated with requests for evaluations and medications to treat ADHD. You may not realize that we didn’t always have ADHD specialists to help us or several dozen stimulant concoctions from which to choose. In the beginning, ADHD specialists had to invent themselves while the pharmaceutical companies scrambled to meet the demand for drugs that were longer lasting and more palatable.
The increasing popularity of professional contact sports is probably what we have to thank for sharpening this focus on head injury. I suspect that, for the general population, there are no more concussions occurring today than there were 50 years ago. However, in the subgroup of professional and elite college athletes, the players’ increasing speed, size, and flagrant ignorance of the rules have resulted in more significant head injuries. When a highly paid megastar athlete must sit out key games, the management of his head injury generates a lot of attention and discussion.
I am sure that there also has been an increase in concussions among young women who now have more opportunities to participate in contact sports. However, I suspect that most of the apparent increase in the diagnosis among high school and younger athletes of both sexes is primarily the result of heightened awareness. I don’t know of data to support or refute this opinion.
I may be wrong about lack of a real increase in concussion injuries, but there can be no arguing about the explosion in the number of clinics and providers who advertise themselves as concussion specialists. Neurologists, psychologists, chiropractors, orthopedists, and sports medicine practitioners and trainers all have climbed on the bandwagon to satisfy the demand generated by this country’s new concussion awareness.
The problem is that, just as in the early days after the “discovery” of ADHD, the science behind much of the advice and management strategies for concussion just isn’t there. For example, resting the brain after a head injury sounds like a good idea. After all, it works for a torn hamstring. However, “sounds like” and “is” are two very different things.
In an excellent article in this publication (“Spotlight shifts to active treatment for concussions,” by Christine Kilgore), I found some comforting news that concussion management may be taking some baby steps into the realm of evidence-based decision management. The original results came from a pediatric population, but it now appears that prolonged rest, which is routinely recommended, can be counterproductive in many concussed patients. The physicians quoted in this article suggest that their experience is pointing to the need for active management in patients with a variety of postconcussion symptoms. Brian Hainline, MD, a clinical professor of neurology at New York University and Indiana University, Indianapolis, observes, “It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged.”
Of course, the science is still lagging behind and the observations by the physicians quoted in this article are based on small series, but their agreement deserves our attention. I urge you to take a look at this article to get an idea of where the management of concussion appears to be going. Not surprisingly, no two concussion patients are the same, and their management should be tailored to their needs. Reliance on overly simplistic guidelines not only doesn’t work but can do harm. It’s that old Hippocratic Oath thing again.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Those of you who were in high school or middle school in 1987, when the DSM II-R first included “Attention Deficit Disorder With and Without Hyperactivity” for the first time, missed out on the “discovery,” and subsequent commercialization, of a condition that had been percolating under physicians’ noses for hundreds of years.
You may have wondered what primary care physicians did with their time before they were inundated with requests for evaluations and medications to treat ADHD. You may not realize that we didn’t always have ADHD specialists to help us or several dozen stimulant concoctions from which to choose. In the beginning, ADHD specialists had to invent themselves while the pharmaceutical companies scrambled to meet the demand for drugs that were longer lasting and more palatable.
The increasing popularity of professional contact sports is probably what we have to thank for sharpening this focus on head injury. I suspect that, for the general population, there are no more concussions occurring today than there were 50 years ago. However, in the subgroup of professional and elite college athletes, the players’ increasing speed, size, and flagrant ignorance of the rules have resulted in more significant head injuries. When a highly paid megastar athlete must sit out key games, the management of his head injury generates a lot of attention and discussion.
I am sure that there also has been an increase in concussions among young women who now have more opportunities to participate in contact sports. However, I suspect that most of the apparent increase in the diagnosis among high school and younger athletes of both sexes is primarily the result of heightened awareness. I don’t know of data to support or refute this opinion.
I may be wrong about lack of a real increase in concussion injuries, but there can be no arguing about the explosion in the number of clinics and providers who advertise themselves as concussion specialists. Neurologists, psychologists, chiropractors, orthopedists, and sports medicine practitioners and trainers all have climbed on the bandwagon to satisfy the demand generated by this country’s new concussion awareness.
The problem is that, just as in the early days after the “discovery” of ADHD, the science behind much of the advice and management strategies for concussion just isn’t there. For example, resting the brain after a head injury sounds like a good idea. After all, it works for a torn hamstring. However, “sounds like” and “is” are two very different things.
In an excellent article in this publication (“Spotlight shifts to active treatment for concussions,” by Christine Kilgore), I found some comforting news that concussion management may be taking some baby steps into the realm of evidence-based decision management. The original results came from a pediatric population, but it now appears that prolonged rest, which is routinely recommended, can be counterproductive in many concussed patients. The physicians quoted in this article suggest that their experience is pointing to the need for active management in patients with a variety of postconcussion symptoms. Brian Hainline, MD, a clinical professor of neurology at New York University and Indiana University, Indianapolis, observes, “It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged.”
Of course, the science is still lagging behind and the observations by the physicians quoted in this article are based on small series, but their agreement deserves our attention. I urge you to take a look at this article to get an idea of where the management of concussion appears to be going. Not surprisingly, no two concussion patients are the same, and their management should be tailored to their needs. Reliance on overly simplistic guidelines not only doesn’t work but can do harm. It’s that old Hippocratic Oath thing again.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Fat City
“Honey, does this town make me look fat?”
“Yes, Dear, I’m afraid it does.”
No, that really wasn’t a typo in the first line. I intended to type “town” and not “gown.” A recent article by Dionysus Powell in healthcareinamerica.us has prompted me to think a bit more about the relationship between obesity and the communities we inhabit (“Fit Cities vs. Fat Cities – What available data can tell us about the difference in lifestyle and obesity between cities,” by Dionysus Powell, March 28, 2017). The author is a biotech researcher who has collected readily available Centers for Disease Control and Prevention data on body mass index (BMI) and self-reported sedentary behavior in almost 200 U.S. cities. He then sliced and diced these numbers with each cities’ walkability score, which is a crude measure of how easily citizens and visitors on foot can reach a variety of destinations such as shops, schools, churches, libraries, and municipal offices. You can easily find your own town’s score by going to walkscore.com.
Not surprisingly, the author discovered that “differences in obesity rates between cities can largely be explained by differences in physical activity.” Of course, there is a point at which a community has sufficient walkable infrastructure so that its obesity rate is a result of the citizens choosing not to walk rather than the community’s failure to provide pedestrians with enough connectivity to do their daily errands on foot. That threshold point appears to be a walkability score of 50, yet Mr. Powell observes that most American cities fail to reach even that minimum.
Although rich people tend to have better health outcomes than poor people, and there is a “general trend for richer cities to be more physically active than poorer cities,” Mr. Powell could not find a relationship between a city’s median income and its walkability.
If, like most of us, you have been frustrated in your efforts to lower the BMI of your patients, it may be time to emerge from the confines of your office and take a look at your town’s walkability score. If it is less than 50, you and your fellow concerned citizens and officials have some work to do. It may mean advocating for improved pedestrian infrastructure and/or dismantling the physical and zoning barriers to pedestrian connectivity. For example, maybe your community should be adding more pedestrian-activated crossing signals or tapping into federal and state safe routes to school programs or adopting zoning ordinances that require sidewalks in all new developments.
Here in Brunswick, we have a very enviable walkability score of 87, meaning “most errands can be accomplished on foot.” We have a bicycle and pedestrian advisory committee that reports to the town council and works with the town engineer to advocate for infrastructure improvements that encourage pedestrian connectivity. However, funding these improvements in walkability is always a challenge. But as the analysis in this recent study suggestions, our biggest challenge continues to be encouraging our citizens to take advantage of our existing pedestrian infrastructure.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
“Honey, does this town make me look fat?”
“Yes, Dear, I’m afraid it does.”
No, that really wasn’t a typo in the first line. I intended to type “town” and not “gown.” A recent article by Dionysus Powell in healthcareinamerica.us has prompted me to think a bit more about the relationship between obesity and the communities we inhabit (“Fit Cities vs. Fat Cities – What available data can tell us about the difference in lifestyle and obesity between cities,” by Dionysus Powell, March 28, 2017). The author is a biotech researcher who has collected readily available Centers for Disease Control and Prevention data on body mass index (BMI) and self-reported sedentary behavior in almost 200 U.S. cities. He then sliced and diced these numbers with each cities’ walkability score, which is a crude measure of how easily citizens and visitors on foot can reach a variety of destinations such as shops, schools, churches, libraries, and municipal offices. You can easily find your own town’s score by going to walkscore.com.
Not surprisingly, the author discovered that “differences in obesity rates between cities can largely be explained by differences in physical activity.” Of course, there is a point at which a community has sufficient walkable infrastructure so that its obesity rate is a result of the citizens choosing not to walk rather than the community’s failure to provide pedestrians with enough connectivity to do their daily errands on foot. That threshold point appears to be a walkability score of 50, yet Mr. Powell observes that most American cities fail to reach even that minimum.
Although rich people tend to have better health outcomes than poor people, and there is a “general trend for richer cities to be more physically active than poorer cities,” Mr. Powell could not find a relationship between a city’s median income and its walkability.
If, like most of us, you have been frustrated in your efforts to lower the BMI of your patients, it may be time to emerge from the confines of your office and take a look at your town’s walkability score. If it is less than 50, you and your fellow concerned citizens and officials have some work to do. It may mean advocating for improved pedestrian infrastructure and/or dismantling the physical and zoning barriers to pedestrian connectivity. For example, maybe your community should be adding more pedestrian-activated crossing signals or tapping into federal and state safe routes to school programs or adopting zoning ordinances that require sidewalks in all new developments.
Here in Brunswick, we have a very enviable walkability score of 87, meaning “most errands can be accomplished on foot.” We have a bicycle and pedestrian advisory committee that reports to the town council and works with the town engineer to advocate for infrastructure improvements that encourage pedestrian connectivity. However, funding these improvements in walkability is always a challenge. But as the analysis in this recent study suggestions, our biggest challenge continues to be encouraging our citizens to take advantage of our existing pedestrian infrastructure.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
“Honey, does this town make me look fat?”
“Yes, Dear, I’m afraid it does.”
No, that really wasn’t a typo in the first line. I intended to type “town” and not “gown.” A recent article by Dionysus Powell in healthcareinamerica.us has prompted me to think a bit more about the relationship between obesity and the communities we inhabit (“Fit Cities vs. Fat Cities – What available data can tell us about the difference in lifestyle and obesity between cities,” by Dionysus Powell, March 28, 2017). The author is a biotech researcher who has collected readily available Centers for Disease Control and Prevention data on body mass index (BMI) and self-reported sedentary behavior in almost 200 U.S. cities. He then sliced and diced these numbers with each cities’ walkability score, which is a crude measure of how easily citizens and visitors on foot can reach a variety of destinations such as shops, schools, churches, libraries, and municipal offices. You can easily find your own town’s score by going to walkscore.com.
Not surprisingly, the author discovered that “differences in obesity rates between cities can largely be explained by differences in physical activity.” Of course, there is a point at which a community has sufficient walkable infrastructure so that its obesity rate is a result of the citizens choosing not to walk rather than the community’s failure to provide pedestrians with enough connectivity to do their daily errands on foot. That threshold point appears to be a walkability score of 50, yet Mr. Powell observes that most American cities fail to reach even that minimum.
Although rich people tend to have better health outcomes than poor people, and there is a “general trend for richer cities to be more physically active than poorer cities,” Mr. Powell could not find a relationship between a city’s median income and its walkability.
If, like most of us, you have been frustrated in your efforts to lower the BMI of your patients, it may be time to emerge from the confines of your office and take a look at your town’s walkability score. If it is less than 50, you and your fellow concerned citizens and officials have some work to do. It may mean advocating for improved pedestrian infrastructure and/or dismantling the physical and zoning barriers to pedestrian connectivity. For example, maybe your community should be adding more pedestrian-activated crossing signals or tapping into federal and state safe routes to school programs or adopting zoning ordinances that require sidewalks in all new developments.
Here in Brunswick, we have a very enviable walkability score of 87, meaning “most errands can be accomplished on foot.” We have a bicycle and pedestrian advisory committee that reports to the town council and works with the town engineer to advocate for infrastructure improvements that encourage pedestrian connectivity. However, funding these improvements in walkability is always a challenge. But as the analysis in this recent study suggestions, our biggest challenge continues to be encouraging our citizens to take advantage of our existing pedestrian infrastructure.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
HIV research update: March 2017
A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
The prevalence of multidrug-resistant gram-negative organisms is significantly higher in HIV-positive males than in HIV-negative males, according to a study in BMC Infectious Diseases.
“[The] effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of [Mycobacterium] tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates,” says a report published in Molecular Biology and Evolution.
A study in AIDS Care found that depression partially mediated the relationship between basic psychological needs and quality of life in people living with HIV, suggesting that basic psychological needs and depression may be specific targets for psychosocial interventions.
HIV-infected participants who took 52 weeks of pitavastatin 4 mg daily (vs. pravastatin 40 mg daily) experienced a greater reduction in select markers of immune activation and arterial inflammation, in a 45-site study.
Plasma soluble CD163 was independently associated with incident chronic kidney disease, chronic lung disease, and liver disease in treated HIV-1 infected individuals, according to a study in the journal AIDS.
The recombinant multiepitope protein MEP1 has the potential to be developed as an effective HIV-1 vaccine candidate, a recent study found, although suitable adjuvant is necessary for this protein to generate protective immune responses.
A study in HIV Clinical Trials found that the drug combination emtricitabine/tenofovir alafenamide offers safety advantages to HIV patients over the combination emtricitabine/tenofovir disoproxil fumarate and can be an important option as a nucleoside reverse transcriptase inhibitor backbone given with a variety of third agents.
A dataset analysis found mortality and CD4 progression rates in HIV-1 infected people exhibited regional and age-specific differences, with decreased survival in African and Southeast Asian/East Asian cohorts compared with European/North American and older age groups.
Residence in supportive housing is associated with improvements in CD4 count and viral load for a sample of formerly homeless persons living with HIV/AIDS, according to an Ohio-based study of 86 participants in a supportive housing program.
People living with HIV have a higher incidence of non–AIDS-defining cancer than does the general population and HCV-coinfection is associated with a higher incidence of non–AIDS-defining cancer.
Higher body mass index, lower apolipoprotein A1 and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection, according to a retrospective study in JAIDS.
A study in the journal AIDS found that alcohol use trajectories characterized by persistent unhealthy drinking are associated with more advanced HIV disease severity among HIV-infected veterans in the United States.
[email protected]
On Twitter @richpizzi
A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
The prevalence of multidrug-resistant gram-negative organisms is significantly higher in HIV-positive males than in HIV-negative males, according to a study in BMC Infectious Diseases.
“[The] effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of [Mycobacterium] tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates,” says a report published in Molecular Biology and Evolution.
A study in AIDS Care found that depression partially mediated the relationship between basic psychological needs and quality of life in people living with HIV, suggesting that basic psychological needs and depression may be specific targets for psychosocial interventions.
HIV-infected participants who took 52 weeks of pitavastatin 4 mg daily (vs. pravastatin 40 mg daily) experienced a greater reduction in select markers of immune activation and arterial inflammation, in a 45-site study.
Plasma soluble CD163 was independently associated with incident chronic kidney disease, chronic lung disease, and liver disease in treated HIV-1 infected individuals, according to a study in the journal AIDS.
The recombinant multiepitope protein MEP1 has the potential to be developed as an effective HIV-1 vaccine candidate, a recent study found, although suitable adjuvant is necessary for this protein to generate protective immune responses.
A study in HIV Clinical Trials found that the drug combination emtricitabine/tenofovir alafenamide offers safety advantages to HIV patients over the combination emtricitabine/tenofovir disoproxil fumarate and can be an important option as a nucleoside reverse transcriptase inhibitor backbone given with a variety of third agents.
A dataset analysis found mortality and CD4 progression rates in HIV-1 infected people exhibited regional and age-specific differences, with decreased survival in African and Southeast Asian/East Asian cohorts compared with European/North American and older age groups.
Residence in supportive housing is associated with improvements in CD4 count and viral load for a sample of formerly homeless persons living with HIV/AIDS, according to an Ohio-based study of 86 participants in a supportive housing program.
People living with HIV have a higher incidence of non–AIDS-defining cancer than does the general population and HCV-coinfection is associated with a higher incidence of non–AIDS-defining cancer.
Higher body mass index, lower apolipoprotein A1 and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection, according to a retrospective study in JAIDS.
A study in the journal AIDS found that alcohol use trajectories characterized by persistent unhealthy drinking are associated with more advanced HIV disease severity among HIV-infected veterans in the United States.
[email protected]
On Twitter @richpizzi
A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
The prevalence of multidrug-resistant gram-negative organisms is significantly higher in HIV-positive males than in HIV-negative males, according to a study in BMC Infectious Diseases.
“[The] effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of [Mycobacterium] tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates,” says a report published in Molecular Biology and Evolution.
A study in AIDS Care found that depression partially mediated the relationship between basic psychological needs and quality of life in people living with HIV, suggesting that basic psychological needs and depression may be specific targets for psychosocial interventions.
HIV-infected participants who took 52 weeks of pitavastatin 4 mg daily (vs. pravastatin 40 mg daily) experienced a greater reduction in select markers of immune activation and arterial inflammation, in a 45-site study.
Plasma soluble CD163 was independently associated with incident chronic kidney disease, chronic lung disease, and liver disease in treated HIV-1 infected individuals, according to a study in the journal AIDS.
The recombinant multiepitope protein MEP1 has the potential to be developed as an effective HIV-1 vaccine candidate, a recent study found, although suitable adjuvant is necessary for this protein to generate protective immune responses.
A study in HIV Clinical Trials found that the drug combination emtricitabine/tenofovir alafenamide offers safety advantages to HIV patients over the combination emtricitabine/tenofovir disoproxil fumarate and can be an important option as a nucleoside reverse transcriptase inhibitor backbone given with a variety of third agents.
A dataset analysis found mortality and CD4 progression rates in HIV-1 infected people exhibited regional and age-specific differences, with decreased survival in African and Southeast Asian/East Asian cohorts compared with European/North American and older age groups.
Residence in supportive housing is associated with improvements in CD4 count and viral load for a sample of formerly homeless persons living with HIV/AIDS, according to an Ohio-based study of 86 participants in a supportive housing program.
People living with HIV have a higher incidence of non–AIDS-defining cancer than does the general population and HCV-coinfection is associated with a higher incidence of non–AIDS-defining cancer.
Higher body mass index, lower apolipoprotein A1 and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection, according to a retrospective study in JAIDS.
A study in the journal AIDS found that alcohol use trajectories characterized by persistent unhealthy drinking are associated with more advanced HIV disease severity among HIV-infected veterans in the United States.
[email protected]
On Twitter @richpizzi
Pegylated interferon alfa-2a induces durable responses in MPNs
Pegylated interferon alfa-2a can induce durable hematologic and molecular responses in patients with advanced essential thrombocythemia and polycythemia vera, according to a post hoc analysis of data from a prospective, open-label, phase II trial.
Of 83 patients treated with pegylated interferon alfa-2a, 66 (80%) experienced hematological response, and of 55 of the 83 who were positive for the JAK2 Val617 mutation and who were evaluable for a molecular response, 35 (64%) experienced molecular response. The median response durations were 66 months and 53 months, respectively, wrote Lucia Masarova, MD, and her colleagues at MD Anderson Cancer Center, Houston.
Of the 66 hematological responders, 26 (39%) maintained some response during a median follow-up of 83 months. Among the 40 who lost their response, 19 had dose reductions or had the drug withheld because of intolerance or toxicity, 1 developed concurrent diffuse large B-cell lymphoma, and 20 progressed despite treatment with the highest tolerable dose of pegylated interferon alfa-2a. Of note, 7 (28%) of 25 patients who were treated for at least 46 months (median of 77 months) sustained their hematologic response for a median of 6 months after discontinuation of therapy, the investigators said (Lancet Haematol. 2017 Apr;4:e165-75).
Of the 35 molecular responders, 25 (71%) maintained some response during follow-up. Of the nine evaluable patients who did not maintain response (the 10th patient was taken off the study because of concurrent non-Hodgkin lymphoma) four lost response at a median of 2 years after the drug was withheld, and five lost response while on therapy. Three maintained their complete molecular remission – for 18, 55, and 79 months – after discontinuation of therapy.
“Only one patient who achieved a complete molecular remission has relapsed after stopping therapy for 16 months (complete molecular remission duration, 66 months). The other 9 of 10 patients had durable remissions (median duration 69 months),” the investigators wrote, noting that among the 20 patients with a partial molecular remission, 5 (25%) sustained best partial remission, 7 (28%) are in minor molecular remission, 8 (32%) lost their response, and 3 of 5 (60%) with minor molecular remission sustained that remission.
The study comprised adults over age 18 years who were diagnosed with essential thrombocythemia (40 patients) or polycythemia vera (43) and were enrolled during May 2005 to October 2009. Of the 83 patients, 52 (63%) had received some form of therapy prior to enrollment, including 14 who were treated with standard interferon alfa-2a and 1 who was treated with pegylated interferon alfa-2a. The initial starting dose of pegylated interferon alfa-2a used in the study was 450 mcg delivered subcutaneously once each week, but the dose was decreased in a stepwise manner to a final starting dose of 90 mcg per week due to toxicity; starting doses include 450 mcg in 3 patients, 360 mcg in 3 patients, 270 mcg in 19 patients, 180 mcg in 26 patients, and 90 mcg in 32 patients). Treatment continued as long as clinical benefit continued, and hematological responses were assessed every 3-6 months.
Treatment-related toxicities decreased over time, but five patients had treatment-limiting grade 3 or 4 toxicities after 60 months on therapy; overall 18 patients (22%) discontinued treatment due to toxicity.
The therapeutic approach to essential thrombocythemia and polycythemia vera has mainly focused on control of blood counts and reduction of the risk of thrombosis. Those at high risk for thrombosis generally undergo cytoreductive therapy with hydroxyurea. Recombinant interferon alfa is an alternative to hydroxyurea “given its biological, anti-proliferative, immunomodulating, and anticlonal effects,” the investigators explained.
“However, the widespread use of this biological drug has been limited by high rates of discontinuation due to side effects. Pegylated forms of interferon have a better pharmacological profile than short-acting interferons: they require less frequent injection, lower immunogenicity, and possibly fewer toxic effects,” they said.
Although pegylated interferon-alfa 2a has shown promise in several trials, most had short follow-up. The nearly 7 years of follow-up in the current trial is almost twice as long as in those prior studies.
During the current study, including follow-up, eight major vascular thromboembolic events occurred. One was associated with heart catheterization, one with elective chest surgery, and one with an angiogram. The remaining five occurred with no discernible cause after a median of 38 months of therapy for an incidence of 1.22 unprovoked vascular thromboembolic events per 100 person-years, and three of those were in patients with complete hematologic response. Two of the five patients were under age 60 years and had no history of thrombosis. Another patient had a serious unprovoked cerebrovascular hemorrhage after 3 years on therapy and while in complete hematological response.
In addition, 7 of the 83 patients in the study had disease progression on therapy; 6 progressed to myelofibrosis, and 1 developed acute myeloid leukemia. The median time to transformation in these patients was 40 months.
At the time of publication, 32 patient remained in the study and 24 were receiving treatment. Nineteen were in hematologic response at last follow-up, and most (75%) were on a dose of 90 mcg or less per week.
In addition to showing that some patients achieve durable responses on pegylated interferon alfa-2a, this study provided five important observations, the investigators said: 1) Patients might continue to derive clinical benefit from pegylated interferon alfa-2a even after losing response. 2) Only complete molecular remissions are durable, and some cases can be sustained after therapy discontinuation. 3) Clinical activity of pegylated interferon alfa-2a is not correlated with JAK2 mutation status. 4) Toxic effects unrelated to dose may develop and can be treatment-limiting, even after a long exposure to the drug. 5) Disease-related vascular complications or progression to myelofibrosis can still occur in patients on therapy.
“Our findings suggest that pegylated interferon alfa-2a is a viable treatment option, especially for young patients who want to avoid prolonged cytotoxic therapy. Lower doses minimize side effects while retaining efficacy,” they wrote, suggesting – based on these and other results – a starting dose of 45 mcg weekly to limit adverse events and maximize response.
They also noted that treated patients with a history of autoimmune disease and those with mood disorder should be monitored closely for side effects.
Future studies on pegylated interferon afla-2a alone or in combination with novel immunomodulatory drugs are needed to identify patients who would benefit most from treatment, and additional objective response criteria, such as measurement of spleen size, bone marrow histology, and quality of life should be used to better assess clinical benefit, they said.
The National Cancer Institute funded the study. The authors reported having no disclosures.
The finding by Masarova et al. that interferon alfa induces durable responses that persist even after stopping treatment in a relatively large proportion of patients contradicts the main issues raised against use of interferon alfa in this setting, Jean-Jacques Kiladjian, MD, said in an editorial.
For example, despite concerns about side effects and an inability of patients to tolerate interferon alfa, the findings confirm that it can control myeloproliferative neoplasms at reduced doses, with toxicity similar to that reported with hydroxyurea and, importantly, with no new safety issues noted, he said.
Further, the findings underscore the value of achieving a molecular response, which is a subject of debate.
“In particular, patients who achieved complete molecular response derived the longest clinical benefit and none of them had disease progression,” he wrote (Lancet Haematol. 2017 Apr;4:e150-1).
While the investigators did not note a clear decrease in the expected incidence of transformation to myelofibrosis or acute leukemia among study participants, they did “underline the limitations of this study for accurate estimation of these events,” and two ongoing studies comparing interferon alfa and hydroxyurea in much larger cohorts (the Proud-PV and MPD-RC 112 studies) should provide stronger evidence regarding the leukemogenic potential of the therapies, he said.
Dr. Kiladjian is with Assistance Publique–Hopitaux de Paris and Centre d’Investigations Cliniques, Hopital Saint-Louis, Université Paris Diderot, France. He reported receiving institutional research grants from Novartis and AOP Orphan, and serving as an advisory board member for Novartis, AOP Orphan, and Shire.
The finding by Masarova et al. that interferon alfa induces durable responses that persist even after stopping treatment in a relatively large proportion of patients contradicts the main issues raised against use of interferon alfa in this setting, Jean-Jacques Kiladjian, MD, said in an editorial.
For example, despite concerns about side effects and an inability of patients to tolerate interferon alfa, the findings confirm that it can control myeloproliferative neoplasms at reduced doses, with toxicity similar to that reported with hydroxyurea and, importantly, with no new safety issues noted, he said.
Further, the findings underscore the value of achieving a molecular response, which is a subject of debate.
“In particular, patients who achieved complete molecular response derived the longest clinical benefit and none of them had disease progression,” he wrote (Lancet Haematol. 2017 Apr;4:e150-1).
While the investigators did not note a clear decrease in the expected incidence of transformation to myelofibrosis or acute leukemia among study participants, they did “underline the limitations of this study for accurate estimation of these events,” and two ongoing studies comparing interferon alfa and hydroxyurea in much larger cohorts (the Proud-PV and MPD-RC 112 studies) should provide stronger evidence regarding the leukemogenic potential of the therapies, he said.
Dr. Kiladjian is with Assistance Publique–Hopitaux de Paris and Centre d’Investigations Cliniques, Hopital Saint-Louis, Université Paris Diderot, France. He reported receiving institutional research grants from Novartis and AOP Orphan, and serving as an advisory board member for Novartis, AOP Orphan, and Shire.
The finding by Masarova et al. that interferon alfa induces durable responses that persist even after stopping treatment in a relatively large proportion of patients contradicts the main issues raised against use of interferon alfa in this setting, Jean-Jacques Kiladjian, MD, said in an editorial.
For example, despite concerns about side effects and an inability of patients to tolerate interferon alfa, the findings confirm that it can control myeloproliferative neoplasms at reduced doses, with toxicity similar to that reported with hydroxyurea and, importantly, with no new safety issues noted, he said.
Further, the findings underscore the value of achieving a molecular response, which is a subject of debate.
“In particular, patients who achieved complete molecular response derived the longest clinical benefit and none of them had disease progression,” he wrote (Lancet Haematol. 2017 Apr;4:e150-1).
While the investigators did not note a clear decrease in the expected incidence of transformation to myelofibrosis or acute leukemia among study participants, they did “underline the limitations of this study for accurate estimation of these events,” and two ongoing studies comparing interferon alfa and hydroxyurea in much larger cohorts (the Proud-PV and MPD-RC 112 studies) should provide stronger evidence regarding the leukemogenic potential of the therapies, he said.
Dr. Kiladjian is with Assistance Publique–Hopitaux de Paris and Centre d’Investigations Cliniques, Hopital Saint-Louis, Université Paris Diderot, France. He reported receiving institutional research grants from Novartis and AOP Orphan, and serving as an advisory board member for Novartis, AOP Orphan, and Shire.
Pegylated interferon alfa-2a can induce durable hematologic and molecular responses in patients with advanced essential thrombocythemia and polycythemia vera, according to a post hoc analysis of data from a prospective, open-label, phase II trial.
Of 83 patients treated with pegylated interferon alfa-2a, 66 (80%) experienced hematological response, and of 55 of the 83 who were positive for the JAK2 Val617 mutation and who were evaluable for a molecular response, 35 (64%) experienced molecular response. The median response durations were 66 months and 53 months, respectively, wrote Lucia Masarova, MD, and her colleagues at MD Anderson Cancer Center, Houston.
Of the 66 hematological responders, 26 (39%) maintained some response during a median follow-up of 83 months. Among the 40 who lost their response, 19 had dose reductions or had the drug withheld because of intolerance or toxicity, 1 developed concurrent diffuse large B-cell lymphoma, and 20 progressed despite treatment with the highest tolerable dose of pegylated interferon alfa-2a. Of note, 7 (28%) of 25 patients who were treated for at least 46 months (median of 77 months) sustained their hematologic response for a median of 6 months after discontinuation of therapy, the investigators said (Lancet Haematol. 2017 Apr;4:e165-75).
Of the 35 molecular responders, 25 (71%) maintained some response during follow-up. Of the nine evaluable patients who did not maintain response (the 10th patient was taken off the study because of concurrent non-Hodgkin lymphoma) four lost response at a median of 2 years after the drug was withheld, and five lost response while on therapy. Three maintained their complete molecular remission – for 18, 55, and 79 months – after discontinuation of therapy.
“Only one patient who achieved a complete molecular remission has relapsed after stopping therapy for 16 months (complete molecular remission duration, 66 months). The other 9 of 10 patients had durable remissions (median duration 69 months),” the investigators wrote, noting that among the 20 patients with a partial molecular remission, 5 (25%) sustained best partial remission, 7 (28%) are in minor molecular remission, 8 (32%) lost their response, and 3 of 5 (60%) with minor molecular remission sustained that remission.
The study comprised adults over age 18 years who were diagnosed with essential thrombocythemia (40 patients) or polycythemia vera (43) and were enrolled during May 2005 to October 2009. Of the 83 patients, 52 (63%) had received some form of therapy prior to enrollment, including 14 who were treated with standard interferon alfa-2a and 1 who was treated with pegylated interferon alfa-2a. The initial starting dose of pegylated interferon alfa-2a used in the study was 450 mcg delivered subcutaneously once each week, but the dose was decreased in a stepwise manner to a final starting dose of 90 mcg per week due to toxicity; starting doses include 450 mcg in 3 patients, 360 mcg in 3 patients, 270 mcg in 19 patients, 180 mcg in 26 patients, and 90 mcg in 32 patients). Treatment continued as long as clinical benefit continued, and hematological responses were assessed every 3-6 months.
Treatment-related toxicities decreased over time, but five patients had treatment-limiting grade 3 or 4 toxicities after 60 months on therapy; overall 18 patients (22%) discontinued treatment due to toxicity.
The therapeutic approach to essential thrombocythemia and polycythemia vera has mainly focused on control of blood counts and reduction of the risk of thrombosis. Those at high risk for thrombosis generally undergo cytoreductive therapy with hydroxyurea. Recombinant interferon alfa is an alternative to hydroxyurea “given its biological, anti-proliferative, immunomodulating, and anticlonal effects,” the investigators explained.
“However, the widespread use of this biological drug has been limited by high rates of discontinuation due to side effects. Pegylated forms of interferon have a better pharmacological profile than short-acting interferons: they require less frequent injection, lower immunogenicity, and possibly fewer toxic effects,” they said.
Although pegylated interferon-alfa 2a has shown promise in several trials, most had short follow-up. The nearly 7 years of follow-up in the current trial is almost twice as long as in those prior studies.
During the current study, including follow-up, eight major vascular thromboembolic events occurred. One was associated with heart catheterization, one with elective chest surgery, and one with an angiogram. The remaining five occurred with no discernible cause after a median of 38 months of therapy for an incidence of 1.22 unprovoked vascular thromboembolic events per 100 person-years, and three of those were in patients with complete hematologic response. Two of the five patients were under age 60 years and had no history of thrombosis. Another patient had a serious unprovoked cerebrovascular hemorrhage after 3 years on therapy and while in complete hematological response.
In addition, 7 of the 83 patients in the study had disease progression on therapy; 6 progressed to myelofibrosis, and 1 developed acute myeloid leukemia. The median time to transformation in these patients was 40 months.
At the time of publication, 32 patient remained in the study and 24 were receiving treatment. Nineteen were in hematologic response at last follow-up, and most (75%) were on a dose of 90 mcg or less per week.
In addition to showing that some patients achieve durable responses on pegylated interferon alfa-2a, this study provided five important observations, the investigators said: 1) Patients might continue to derive clinical benefit from pegylated interferon alfa-2a even after losing response. 2) Only complete molecular remissions are durable, and some cases can be sustained after therapy discontinuation. 3) Clinical activity of pegylated interferon alfa-2a is not correlated with JAK2 mutation status. 4) Toxic effects unrelated to dose may develop and can be treatment-limiting, even after a long exposure to the drug. 5) Disease-related vascular complications or progression to myelofibrosis can still occur in patients on therapy.
“Our findings suggest that pegylated interferon alfa-2a is a viable treatment option, especially for young patients who want to avoid prolonged cytotoxic therapy. Lower doses minimize side effects while retaining efficacy,” they wrote, suggesting – based on these and other results – a starting dose of 45 mcg weekly to limit adverse events and maximize response.
They also noted that treated patients with a history of autoimmune disease and those with mood disorder should be monitored closely for side effects.
Future studies on pegylated interferon afla-2a alone or in combination with novel immunomodulatory drugs are needed to identify patients who would benefit most from treatment, and additional objective response criteria, such as measurement of spleen size, bone marrow histology, and quality of life should be used to better assess clinical benefit, they said.
The National Cancer Institute funded the study. The authors reported having no disclosures.
Pegylated interferon alfa-2a can induce durable hematologic and molecular responses in patients with advanced essential thrombocythemia and polycythemia vera, according to a post hoc analysis of data from a prospective, open-label, phase II trial.
Of 83 patients treated with pegylated interferon alfa-2a, 66 (80%) experienced hematological response, and of 55 of the 83 who were positive for the JAK2 Val617 mutation and who were evaluable for a molecular response, 35 (64%) experienced molecular response. The median response durations were 66 months and 53 months, respectively, wrote Lucia Masarova, MD, and her colleagues at MD Anderson Cancer Center, Houston.
Of the 66 hematological responders, 26 (39%) maintained some response during a median follow-up of 83 months. Among the 40 who lost their response, 19 had dose reductions or had the drug withheld because of intolerance or toxicity, 1 developed concurrent diffuse large B-cell lymphoma, and 20 progressed despite treatment with the highest tolerable dose of pegylated interferon alfa-2a. Of note, 7 (28%) of 25 patients who were treated for at least 46 months (median of 77 months) sustained their hematologic response for a median of 6 months after discontinuation of therapy, the investigators said (Lancet Haematol. 2017 Apr;4:e165-75).
Of the 35 molecular responders, 25 (71%) maintained some response during follow-up. Of the nine evaluable patients who did not maintain response (the 10th patient was taken off the study because of concurrent non-Hodgkin lymphoma) four lost response at a median of 2 years after the drug was withheld, and five lost response while on therapy. Three maintained their complete molecular remission – for 18, 55, and 79 months – after discontinuation of therapy.
“Only one patient who achieved a complete molecular remission has relapsed after stopping therapy for 16 months (complete molecular remission duration, 66 months). The other 9 of 10 patients had durable remissions (median duration 69 months),” the investigators wrote, noting that among the 20 patients with a partial molecular remission, 5 (25%) sustained best partial remission, 7 (28%) are in minor molecular remission, 8 (32%) lost their response, and 3 of 5 (60%) with minor molecular remission sustained that remission.
The study comprised adults over age 18 years who were diagnosed with essential thrombocythemia (40 patients) or polycythemia vera (43) and were enrolled during May 2005 to October 2009. Of the 83 patients, 52 (63%) had received some form of therapy prior to enrollment, including 14 who were treated with standard interferon alfa-2a and 1 who was treated with pegylated interferon alfa-2a. The initial starting dose of pegylated interferon alfa-2a used in the study was 450 mcg delivered subcutaneously once each week, but the dose was decreased in a stepwise manner to a final starting dose of 90 mcg per week due to toxicity; starting doses include 450 mcg in 3 patients, 360 mcg in 3 patients, 270 mcg in 19 patients, 180 mcg in 26 patients, and 90 mcg in 32 patients). Treatment continued as long as clinical benefit continued, and hematological responses were assessed every 3-6 months.
Treatment-related toxicities decreased over time, but five patients had treatment-limiting grade 3 or 4 toxicities after 60 months on therapy; overall 18 patients (22%) discontinued treatment due to toxicity.
The therapeutic approach to essential thrombocythemia and polycythemia vera has mainly focused on control of blood counts and reduction of the risk of thrombosis. Those at high risk for thrombosis generally undergo cytoreductive therapy with hydroxyurea. Recombinant interferon alfa is an alternative to hydroxyurea “given its biological, anti-proliferative, immunomodulating, and anticlonal effects,” the investigators explained.
“However, the widespread use of this biological drug has been limited by high rates of discontinuation due to side effects. Pegylated forms of interferon have a better pharmacological profile than short-acting interferons: they require less frequent injection, lower immunogenicity, and possibly fewer toxic effects,” they said.
Although pegylated interferon-alfa 2a has shown promise in several trials, most had short follow-up. The nearly 7 years of follow-up in the current trial is almost twice as long as in those prior studies.
During the current study, including follow-up, eight major vascular thromboembolic events occurred. One was associated with heart catheterization, one with elective chest surgery, and one with an angiogram. The remaining five occurred with no discernible cause after a median of 38 months of therapy for an incidence of 1.22 unprovoked vascular thromboembolic events per 100 person-years, and three of those were in patients with complete hematologic response. Two of the five patients were under age 60 years and had no history of thrombosis. Another patient had a serious unprovoked cerebrovascular hemorrhage after 3 years on therapy and while in complete hematological response.
In addition, 7 of the 83 patients in the study had disease progression on therapy; 6 progressed to myelofibrosis, and 1 developed acute myeloid leukemia. The median time to transformation in these patients was 40 months.
At the time of publication, 32 patient remained in the study and 24 were receiving treatment. Nineteen were in hematologic response at last follow-up, and most (75%) were on a dose of 90 mcg or less per week.
In addition to showing that some patients achieve durable responses on pegylated interferon alfa-2a, this study provided five important observations, the investigators said: 1) Patients might continue to derive clinical benefit from pegylated interferon alfa-2a even after losing response. 2) Only complete molecular remissions are durable, and some cases can be sustained after therapy discontinuation. 3) Clinical activity of pegylated interferon alfa-2a is not correlated with JAK2 mutation status. 4) Toxic effects unrelated to dose may develop and can be treatment-limiting, even after a long exposure to the drug. 5) Disease-related vascular complications or progression to myelofibrosis can still occur in patients on therapy.
“Our findings suggest that pegylated interferon alfa-2a is a viable treatment option, especially for young patients who want to avoid prolonged cytotoxic therapy. Lower doses minimize side effects while retaining efficacy,” they wrote, suggesting – based on these and other results – a starting dose of 45 mcg weekly to limit adverse events and maximize response.
They also noted that treated patients with a history of autoimmune disease and those with mood disorder should be monitored closely for side effects.
Future studies on pegylated interferon afla-2a alone or in combination with novel immunomodulatory drugs are needed to identify patients who would benefit most from treatment, and additional objective response criteria, such as measurement of spleen size, bone marrow histology, and quality of life should be used to better assess clinical benefit, they said.
The National Cancer Institute funded the study. The authors reported having no disclosures.
FROM THE LANCET HAEMATOLOGY
Key clinical point:
Major finding: Eighty percent of patients experienced hematological response and 64% experienced molecular response. The median response durations were 66 months and 53 months, respectively.
Data source: A post hoc analysis of data from an open-label, phase II study of 83 patients.
Disclosures: The National Cancer Institute funded the study. The authors reported having no disclosures.
Statins in HIV-positive patients are a missed opportunity
WASHINGTON – Only one in four U.S. adults with known HIV infection is on statin therapy, even though premature coronary heart disease has become a leading cause of morbidity and mortality for HIV-positive individuals in an era of greatly extended life expectancy due to highly active antiretroviral therapy, Robert S. Rosenson, MD, reported at the annual meeting of the American College of Cardiology.
Not only are statins greatly underutilized in HIV-positive patients, but in a large national observational study, 8% of those who were on a statin were on one that was contraindicated because of concomitant use of antiretroviral therapy or other agents posing a risk for major drug interactions, added Dr. Rosenson, professor of medicine and director of cardiometabolic disorders at Icahn School of Medicine at Mount Sinai, New York.
He presented a retrospective cohort study of 23,119 HIV-positive U.S. adults with commercial health insurance in 2014. The data source was the MarketScan database.
During the study year, 5,931 HIV-positive adults (26%) were taking a statin. In a multivariate regression analysis, factors associated with increased likelihood of statin therapy were age 50 years or older, male gender, known coronary heart disease, hypertension, and diabetes.
A total of 491 patients were taking a contraindicated statin or a statin at too high a dose to be safe, given the other medications they were on.
The protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and some statins are metabolized by the cytochrome P450 isoenzyme CYP3A4. As a consequence, areas under the curve for simvastatin and lovastatin skyrocket when those statins are given with some protease inhibitors, placing patients at increased risk for myopathy, including rhabdomyolysis.
As a consequence, simvastatin and lovastatin are widely considered contraindicated in HIV-positive patients.
Infectious Diseases Society of America guidelines recommend pravastatin or low-dose atorvastatin at 10 mg/day as first-line therapy for lipid-lowering and cardiovascular risk reduction in HIV-positive patients, with fluvastatin a reasonable alternative.
Dr. Rosenson noted that in his study, 62% of the HIV-infected patients on a contraindicated statin were taking a protease inhibitor, 29% were on gemfibrozil (Lopid), and the remaining handful were on other agents posing significant risk of drug interactions, including azole antifungals, calcium channel blockers, or cobicistat (Tybost).
The statin study was jointly funded by Amgen, Mount Sinai, and the University of Alabama. Dr. Rosenson reported serving as a consultant to Amgen, Eli Lilly, Regeneron, and Sanofi.
WASHINGTON – Only one in four U.S. adults with known HIV infection is on statin therapy, even though premature coronary heart disease has become a leading cause of morbidity and mortality for HIV-positive individuals in an era of greatly extended life expectancy due to highly active antiretroviral therapy, Robert S. Rosenson, MD, reported at the annual meeting of the American College of Cardiology.
Not only are statins greatly underutilized in HIV-positive patients, but in a large national observational study, 8% of those who were on a statin were on one that was contraindicated because of concomitant use of antiretroviral therapy or other agents posing a risk for major drug interactions, added Dr. Rosenson, professor of medicine and director of cardiometabolic disorders at Icahn School of Medicine at Mount Sinai, New York.
He presented a retrospective cohort study of 23,119 HIV-positive U.S. adults with commercial health insurance in 2014. The data source was the MarketScan database.
During the study year, 5,931 HIV-positive adults (26%) were taking a statin. In a multivariate regression analysis, factors associated with increased likelihood of statin therapy were age 50 years or older, male gender, known coronary heart disease, hypertension, and diabetes.
A total of 491 patients were taking a contraindicated statin or a statin at too high a dose to be safe, given the other medications they were on.
The protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and some statins are metabolized by the cytochrome P450 isoenzyme CYP3A4. As a consequence, areas under the curve for simvastatin and lovastatin skyrocket when those statins are given with some protease inhibitors, placing patients at increased risk for myopathy, including rhabdomyolysis.
As a consequence, simvastatin and lovastatin are widely considered contraindicated in HIV-positive patients.
Infectious Diseases Society of America guidelines recommend pravastatin or low-dose atorvastatin at 10 mg/day as first-line therapy for lipid-lowering and cardiovascular risk reduction in HIV-positive patients, with fluvastatin a reasonable alternative.
Dr. Rosenson noted that in his study, 62% of the HIV-infected patients on a contraindicated statin were taking a protease inhibitor, 29% were on gemfibrozil (Lopid), and the remaining handful were on other agents posing significant risk of drug interactions, including azole antifungals, calcium channel blockers, or cobicistat (Tybost).
The statin study was jointly funded by Amgen, Mount Sinai, and the University of Alabama. Dr. Rosenson reported serving as a consultant to Amgen, Eli Lilly, Regeneron, and Sanofi.
WASHINGTON – Only one in four U.S. adults with known HIV infection is on statin therapy, even though premature coronary heart disease has become a leading cause of morbidity and mortality for HIV-positive individuals in an era of greatly extended life expectancy due to highly active antiretroviral therapy, Robert S. Rosenson, MD, reported at the annual meeting of the American College of Cardiology.
Not only are statins greatly underutilized in HIV-positive patients, but in a large national observational study, 8% of those who were on a statin were on one that was contraindicated because of concomitant use of antiretroviral therapy or other agents posing a risk for major drug interactions, added Dr. Rosenson, professor of medicine and director of cardiometabolic disorders at Icahn School of Medicine at Mount Sinai, New York.
He presented a retrospective cohort study of 23,119 HIV-positive U.S. adults with commercial health insurance in 2014. The data source was the MarketScan database.
During the study year, 5,931 HIV-positive adults (26%) were taking a statin. In a multivariate regression analysis, factors associated with increased likelihood of statin therapy were age 50 years or older, male gender, known coronary heart disease, hypertension, and diabetes.
A total of 491 patients were taking a contraindicated statin or a statin at too high a dose to be safe, given the other medications they were on.
The protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and some statins are metabolized by the cytochrome P450 isoenzyme CYP3A4. As a consequence, areas under the curve for simvastatin and lovastatin skyrocket when those statins are given with some protease inhibitors, placing patients at increased risk for myopathy, including rhabdomyolysis.
As a consequence, simvastatin and lovastatin are widely considered contraindicated in HIV-positive patients.
Infectious Diseases Society of America guidelines recommend pravastatin or low-dose atorvastatin at 10 mg/day as first-line therapy for lipid-lowering and cardiovascular risk reduction in HIV-positive patients, with fluvastatin a reasonable alternative.
Dr. Rosenson noted that in his study, 62% of the HIV-infected patients on a contraindicated statin were taking a protease inhibitor, 29% were on gemfibrozil (Lopid), and the remaining handful were on other agents posing significant risk of drug interactions, including azole antifungals, calcium channel blockers, or cobicistat (Tybost).
The statin study was jointly funded by Amgen, Mount Sinai, and the University of Alabama. Dr. Rosenson reported serving as a consultant to Amgen, Eli Lilly, Regeneron, and Sanofi.
AT ACC 2017
Key clinical point:
Major finding: Lipid-lowering in HIV-positive adults can be tricky: Eight percent of those who were on statin therapy were taking a statin contraindicated in HIV-infected individuals.
Data source: A retrospective study of more than 23,000 HIV-positive U.S. adults with commercial health insurance in 2014.
Disclosures: The statin study was jointly funded by Amgen and two U.S. medical schools. Dr. Rosenson reported serving as a consultant to Amgen, Eli Lilly, Regeneron, and Sanofi.