User login
Sixty-five roses
Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.
My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.
away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”
Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).
Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).
Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.
This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.
My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.
I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*
Oh boy. I had to go sit in my office, turn out the lights, and cry.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.
Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.
My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.
away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”
Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).
Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).
Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.
This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.
My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.
I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*
Oh boy. I had to go sit in my office, turn out the lights, and cry.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.
Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.
My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.
away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”
Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).
Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).
Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.
This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.
My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.
I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*
Oh boy. I had to go sit in my office, turn out the lights, and cry.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.
Primary periodic paralysis attacks reduced with long-term dichlorphenamide
AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.
“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.
Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.
In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)
The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.
Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.
The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).
The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).
No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.
Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.
A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.
Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.
AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.
“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.
Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.
In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)
The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.
Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.
The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).
The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).
No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.
Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.
A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.
Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.
AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.
“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.
Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.
In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)
The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.
Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.
The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).
The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).
No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.
Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.
A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.
Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.
REPORTING FROM AANEM
Patients with Charcot-Marie-Tooth disease describe wide range of care
AUSTIN, TEX. – Patients with Charcot-Marie-Tooth disease (CMT) receive a range of supportive care that includes physical therapy, surgery, medications, orthoses, and walking aids, according to patient-reported data presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. Patients describe approaches to CMT management that are broadly consistent with guidelines, researchers said.
“The range of different CMT treatments was wide,” reported Tjalf Ziemssen, MD, PhD, a researcher at Technische Universität Dresden in Germany, and colleagues. “ These results indicate that pain may have a substantial impact on people with CMT.”
The data also suggest that “lower-limb problems and mobility issues have a considerable impact on people with CMT,” they said.
CMT is a rare, progressive neuropathy that leads to distal muscle weakness, muscle atrophy, and sensory loss. There is no cure, and patients rely on supportive care. Until recently, few studies have assessed the impact of CMT on patients’ lives.
An ongoing, international, 2-year observational study is collecting data from adults with CMT. Patients report data via an app called CMT & Me.
To examine patient-reported treatment patterns and care standards for CMT in the United States and the United Kingdom, Dr. Ziemssen and colleagues analyzed data through Aug. 5, 2019, about 9.5 months into the study. Their interim analysis included data from 439 patients, including 222 patients in the United Kingdom and 217 in the United States.
More than 70% of participants visit a family doctor each year, and a similar proportion visit a neurologist. About 40% visit physical therapists, orthotists, or podiatrists. Other health care professionals seen by patients include occupational therapists (20%), orthopedic surgeons (nearly 20%), and pain specialists (about 15%).
About 70% of participants had received rehabilitation therapy such as physical therapy or occupational therapy, and about 70% had used medications, most frequently nonopioid analgesics (about 50%) and antidepressants (about 30%).
More than 80% used orthoses or walking aids, most commonly ankle or leg braces, insoles, or walking sticks.
In addition, about half of respondents had undergone a surgery for CMT. The most common procedures were osteotomy, hammertoe correction, and plantar fascia release.
Together, patients saw about a dozen types of health care professionals. “Small proportions of participants had visited each professional, which suggests that the care requirements of CMT patients are varied,” the researchers said.
The study was sponsored by Pharnext. Dr. Ziemssen and coauthors received compensation for participating in the study. Other coauthors are employees of Pharnext or Vitaccess, the company that developed the app used in the study.
SOURCE: Ziemssen T et al. AANEM 2019. Abstract 83. Treatment of Charcot-Marie-Tooth Disease in the United Kingdom and United States.
AUSTIN, TEX. – Patients with Charcot-Marie-Tooth disease (CMT) receive a range of supportive care that includes physical therapy, surgery, medications, orthoses, and walking aids, according to patient-reported data presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. Patients describe approaches to CMT management that are broadly consistent with guidelines, researchers said.
“The range of different CMT treatments was wide,” reported Tjalf Ziemssen, MD, PhD, a researcher at Technische Universität Dresden in Germany, and colleagues. “ These results indicate that pain may have a substantial impact on people with CMT.”
The data also suggest that “lower-limb problems and mobility issues have a considerable impact on people with CMT,” they said.
CMT is a rare, progressive neuropathy that leads to distal muscle weakness, muscle atrophy, and sensory loss. There is no cure, and patients rely on supportive care. Until recently, few studies have assessed the impact of CMT on patients’ lives.
An ongoing, international, 2-year observational study is collecting data from adults with CMT. Patients report data via an app called CMT & Me.
To examine patient-reported treatment patterns and care standards for CMT in the United States and the United Kingdom, Dr. Ziemssen and colleagues analyzed data through Aug. 5, 2019, about 9.5 months into the study. Their interim analysis included data from 439 patients, including 222 patients in the United Kingdom and 217 in the United States.
More than 70% of participants visit a family doctor each year, and a similar proportion visit a neurologist. About 40% visit physical therapists, orthotists, or podiatrists. Other health care professionals seen by patients include occupational therapists (20%), orthopedic surgeons (nearly 20%), and pain specialists (about 15%).
About 70% of participants had received rehabilitation therapy such as physical therapy or occupational therapy, and about 70% had used medications, most frequently nonopioid analgesics (about 50%) and antidepressants (about 30%).
More than 80% used orthoses or walking aids, most commonly ankle or leg braces, insoles, or walking sticks.
In addition, about half of respondents had undergone a surgery for CMT. The most common procedures were osteotomy, hammertoe correction, and plantar fascia release.
Together, patients saw about a dozen types of health care professionals. “Small proportions of participants had visited each professional, which suggests that the care requirements of CMT patients are varied,” the researchers said.
The study was sponsored by Pharnext. Dr. Ziemssen and coauthors received compensation for participating in the study. Other coauthors are employees of Pharnext or Vitaccess, the company that developed the app used in the study.
SOURCE: Ziemssen T et al. AANEM 2019. Abstract 83. Treatment of Charcot-Marie-Tooth Disease in the United Kingdom and United States.
AUSTIN, TEX. – Patients with Charcot-Marie-Tooth disease (CMT) receive a range of supportive care that includes physical therapy, surgery, medications, orthoses, and walking aids, according to patient-reported data presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. Patients describe approaches to CMT management that are broadly consistent with guidelines, researchers said.
“The range of different CMT treatments was wide,” reported Tjalf Ziemssen, MD, PhD, a researcher at Technische Universität Dresden in Germany, and colleagues. “ These results indicate that pain may have a substantial impact on people with CMT.”
The data also suggest that “lower-limb problems and mobility issues have a considerable impact on people with CMT,” they said.
CMT is a rare, progressive neuropathy that leads to distal muscle weakness, muscle atrophy, and sensory loss. There is no cure, and patients rely on supportive care. Until recently, few studies have assessed the impact of CMT on patients’ lives.
An ongoing, international, 2-year observational study is collecting data from adults with CMT. Patients report data via an app called CMT & Me.
To examine patient-reported treatment patterns and care standards for CMT in the United States and the United Kingdom, Dr. Ziemssen and colleagues analyzed data through Aug. 5, 2019, about 9.5 months into the study. Their interim analysis included data from 439 patients, including 222 patients in the United Kingdom and 217 in the United States.
More than 70% of participants visit a family doctor each year, and a similar proportion visit a neurologist. About 40% visit physical therapists, orthotists, or podiatrists. Other health care professionals seen by patients include occupational therapists (20%), orthopedic surgeons (nearly 20%), and pain specialists (about 15%).
About 70% of participants had received rehabilitation therapy such as physical therapy or occupational therapy, and about 70% had used medications, most frequently nonopioid analgesics (about 50%) and antidepressants (about 30%).
More than 80% used orthoses or walking aids, most commonly ankle or leg braces, insoles, or walking sticks.
In addition, about half of respondents had undergone a surgery for CMT. The most common procedures were osteotomy, hammertoe correction, and plantar fascia release.
Together, patients saw about a dozen types of health care professionals. “Small proportions of participants had visited each professional, which suggests that the care requirements of CMT patients are varied,” the researchers said.
The study was sponsored by Pharnext. Dr. Ziemssen and coauthors received compensation for participating in the study. Other coauthors are employees of Pharnext or Vitaccess, the company that developed the app used in the study.
SOURCE: Ziemssen T et al. AANEM 2019. Abstract 83. Treatment of Charcot-Marie-Tooth Disease in the United Kingdom and United States.
REPORTING FROM AANEM 2019
Researchers identify common reasons for misdiagnosis of ALS
AUSTIN – Lack of upper motor neuron signs on examination, presence of sensory symptoms, and absence of tongue fasciculations are common causes of amyotrophic lateral sclerosis (ALS) misdiagnosis, according to an investigation presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
Because its initial presenting symptoms vary, ALS can be difficult for clinicians to diagnose. A diagnostic error may prompt clinicians and patients to pursue ineffective and potentially harmful medical or surgical interventions. Research suggests that surgery, for example, hastens the progression of ALS.
Catherine Rodriguez, a medical student at University of Missouri in Columbia, and colleagues conducted a study to identify the clinical factors and types of cognitive errors that can result in misdiagnosis of ALS. The researchers analyzed electronic medical records of 88 patients with a diagnosis of ALS who were receiving treatment at the University of Missouri Hospital during 2011-2017 with at least 1 year of follow-up. They collected demographic information and clinical characteristics (e.g., ALS Functional Rating Scale and site of symptom onset) for each patient. If a patient received an incorrect diagnosis, Ms. Rodriguez and colleagues recorded the number of physicians he or she had seen, the incorrect diagnosis, the treatment, the type of diagnostic error, the clinical factors contributing to the misdiagnosis, and the type of physician who gave the incorrect diagnosis.
The investigators classed diagnostic errors according to the four categories of cognitive bias of the Patient Safety Network. The categories are availability heuristic (i.e., the diagnosis of a current patient is biased by the clinician’s experience with previous cases), anchoring heuristic (i.e., relying on the initial impression despite the emergence of evidence that may contradict it), framing effects (i.e., subtle cues and collateral information bias the diagnosis), and blind obedience (i.e., undue reliance on test results or expert opinion). Ms. Rodriguez and colleagues used Fisher’s exact test to perform a statistical analysis of the data.
Thirty-four (39%) of the 88 patients were female, and the populations average age was about 60 years. Eighty patients (91%) were white, six (7%) were black, and two (2%) were Hispanic. Twenty patients (23%) received an incorrect diagnosis. Common incorrect diagnoses included spinal abnormality, Bell’s palsy, myasthenia gravis, ulnar neuropathy, autoimmune motor neuropathy, and stroke.
The investigators observed significant differences in the reasons for misdiagnosis, depending on patient characteristics. Veterans were misdiagnosed because of the availability heuristic, while nonveterans were misdiagnosed because of the anchoring heuristic. Lower-limb onset was most commonly misdiagnosed because of the anchoring heuristic. Bulbar onset was most commonly misdiagnosed because of the availability heuristic. Surgical intervention was the most common treatment for an incorrect diagnosis.
The data serve as a reminder of the prevalence of cognitive biases, said Ms. Rodriguez. “Common things are common, so we tend to stick with those [diagnoses]. Especially with ALS, nobody wants to give anyone that diagnosis.” Clinicians should “recognize that incorrect diagnoses have equally bad outcomes for those patients,” she concluded.
The study was supported by a University of Missouri School of Medicine Summer Research Fellowship Program.
SOURCE: Rodriguez C et al. AANEM 2019. Abstract 10. Diagnostic errors and the implications for amyotrophic lateral sclerosis patients.
AUSTIN – Lack of upper motor neuron signs on examination, presence of sensory symptoms, and absence of tongue fasciculations are common causes of amyotrophic lateral sclerosis (ALS) misdiagnosis, according to an investigation presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
Because its initial presenting symptoms vary, ALS can be difficult for clinicians to diagnose. A diagnostic error may prompt clinicians and patients to pursue ineffective and potentially harmful medical or surgical interventions. Research suggests that surgery, for example, hastens the progression of ALS.
Catherine Rodriguez, a medical student at University of Missouri in Columbia, and colleagues conducted a study to identify the clinical factors and types of cognitive errors that can result in misdiagnosis of ALS. The researchers analyzed electronic medical records of 88 patients with a diagnosis of ALS who were receiving treatment at the University of Missouri Hospital during 2011-2017 with at least 1 year of follow-up. They collected demographic information and clinical characteristics (e.g., ALS Functional Rating Scale and site of symptom onset) for each patient. If a patient received an incorrect diagnosis, Ms. Rodriguez and colleagues recorded the number of physicians he or she had seen, the incorrect diagnosis, the treatment, the type of diagnostic error, the clinical factors contributing to the misdiagnosis, and the type of physician who gave the incorrect diagnosis.
The investigators classed diagnostic errors according to the four categories of cognitive bias of the Patient Safety Network. The categories are availability heuristic (i.e., the diagnosis of a current patient is biased by the clinician’s experience with previous cases), anchoring heuristic (i.e., relying on the initial impression despite the emergence of evidence that may contradict it), framing effects (i.e., subtle cues and collateral information bias the diagnosis), and blind obedience (i.e., undue reliance on test results or expert opinion). Ms. Rodriguez and colleagues used Fisher’s exact test to perform a statistical analysis of the data.
Thirty-four (39%) of the 88 patients were female, and the populations average age was about 60 years. Eighty patients (91%) were white, six (7%) were black, and two (2%) were Hispanic. Twenty patients (23%) received an incorrect diagnosis. Common incorrect diagnoses included spinal abnormality, Bell’s palsy, myasthenia gravis, ulnar neuropathy, autoimmune motor neuropathy, and stroke.
The investigators observed significant differences in the reasons for misdiagnosis, depending on patient characteristics. Veterans were misdiagnosed because of the availability heuristic, while nonveterans were misdiagnosed because of the anchoring heuristic. Lower-limb onset was most commonly misdiagnosed because of the anchoring heuristic. Bulbar onset was most commonly misdiagnosed because of the availability heuristic. Surgical intervention was the most common treatment for an incorrect diagnosis.
The data serve as a reminder of the prevalence of cognitive biases, said Ms. Rodriguez. “Common things are common, so we tend to stick with those [diagnoses]. Especially with ALS, nobody wants to give anyone that diagnosis.” Clinicians should “recognize that incorrect diagnoses have equally bad outcomes for those patients,” she concluded.
The study was supported by a University of Missouri School of Medicine Summer Research Fellowship Program.
SOURCE: Rodriguez C et al. AANEM 2019. Abstract 10. Diagnostic errors and the implications for amyotrophic lateral sclerosis patients.
AUSTIN – Lack of upper motor neuron signs on examination, presence of sensory symptoms, and absence of tongue fasciculations are common causes of amyotrophic lateral sclerosis (ALS) misdiagnosis, according to an investigation presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
Because its initial presenting symptoms vary, ALS can be difficult for clinicians to diagnose. A diagnostic error may prompt clinicians and patients to pursue ineffective and potentially harmful medical or surgical interventions. Research suggests that surgery, for example, hastens the progression of ALS.
Catherine Rodriguez, a medical student at University of Missouri in Columbia, and colleagues conducted a study to identify the clinical factors and types of cognitive errors that can result in misdiagnosis of ALS. The researchers analyzed electronic medical records of 88 patients with a diagnosis of ALS who were receiving treatment at the University of Missouri Hospital during 2011-2017 with at least 1 year of follow-up. They collected demographic information and clinical characteristics (e.g., ALS Functional Rating Scale and site of symptom onset) for each patient. If a patient received an incorrect diagnosis, Ms. Rodriguez and colleagues recorded the number of physicians he or she had seen, the incorrect diagnosis, the treatment, the type of diagnostic error, the clinical factors contributing to the misdiagnosis, and the type of physician who gave the incorrect diagnosis.
The investigators classed diagnostic errors according to the four categories of cognitive bias of the Patient Safety Network. The categories are availability heuristic (i.e., the diagnosis of a current patient is biased by the clinician’s experience with previous cases), anchoring heuristic (i.e., relying on the initial impression despite the emergence of evidence that may contradict it), framing effects (i.e., subtle cues and collateral information bias the diagnosis), and blind obedience (i.e., undue reliance on test results or expert opinion). Ms. Rodriguez and colleagues used Fisher’s exact test to perform a statistical analysis of the data.
Thirty-four (39%) of the 88 patients were female, and the populations average age was about 60 years. Eighty patients (91%) were white, six (7%) were black, and two (2%) were Hispanic. Twenty patients (23%) received an incorrect diagnosis. Common incorrect diagnoses included spinal abnormality, Bell’s palsy, myasthenia gravis, ulnar neuropathy, autoimmune motor neuropathy, and stroke.
The investigators observed significant differences in the reasons for misdiagnosis, depending on patient characteristics. Veterans were misdiagnosed because of the availability heuristic, while nonveterans were misdiagnosed because of the anchoring heuristic. Lower-limb onset was most commonly misdiagnosed because of the anchoring heuristic. Bulbar onset was most commonly misdiagnosed because of the availability heuristic. Surgical intervention was the most common treatment for an incorrect diagnosis.
The data serve as a reminder of the prevalence of cognitive biases, said Ms. Rodriguez. “Common things are common, so we tend to stick with those [diagnoses]. Especially with ALS, nobody wants to give anyone that diagnosis.” Clinicians should “recognize that incorrect diagnoses have equally bad outcomes for those patients,” she concluded.
The study was supported by a University of Missouri School of Medicine Summer Research Fellowship Program.
SOURCE: Rodriguez C et al. AANEM 2019. Abstract 10. Diagnostic errors and the implications for amyotrophic lateral sclerosis patients.
Robot-assisted, gamelike tool effective for classifying ADHD
A novel robot-assisted, gamelike test accurately classified ADHD type in elementary school–aged children, according to Mun-Taek Choi, PhD, and associates.
A total of 326 children in the third and fourth grades were included in the study, 35 of whom had been diagnosed with ADHD and 26 of whom were at risk. For the 10- to 12-minute test, participants followed a robot on a path across a numbered mat while stimuli were shown on a TV with both images and sound, and completed a task at each numbered square, reported Dr. Choi, of Sungkyunkwan University, Suwan, South Korea, and associates. The study was published in the Journal of Intelligent & Robotic Systems.
Inattentive and hyperactive-impulsive behavior was measured by the number of omission and commission errors. Response time and task completion time contributed to the measure of inattentive and hyperactive-impulsive behavior. Working memory deficits were measured as deviations in the prescribed route.
This figure improved over the course of the study as the tool learned more, indicating that generalization errors were not a serious issue for the tool, the investigators noted.
“Unlike conventional questionnaire-based tests, the robot-assisted test increases the accuracy of ADHD diagnosis by directly reflecting the quality of children’s behavior during the activity game with the robot involved in the action. Since the test obtains behavioral patterns and levels using robotic sensing technologies, it can reliably determine the three key elements of ADHD diagnosis: hyperactivity, inattentive behavior, and working memory,” the investigators wrote. Ultimately, Dr. Choi and associates wrote, the tool could help clinicians diagnose childhood ADHD.
The study was funded by the South Korean Ministry of Trade, Industry, & Energy. No disclosures were reported.
SOURCE: Choi M-T et al. J Intell Robot Syst. 2018 Jun 19. doi: 10.1007/s10846-018-0890-9.
A novel robot-assisted, gamelike test accurately classified ADHD type in elementary school–aged children, according to Mun-Taek Choi, PhD, and associates.
A total of 326 children in the third and fourth grades were included in the study, 35 of whom had been diagnosed with ADHD and 26 of whom were at risk. For the 10- to 12-minute test, participants followed a robot on a path across a numbered mat while stimuli were shown on a TV with both images and sound, and completed a task at each numbered square, reported Dr. Choi, of Sungkyunkwan University, Suwan, South Korea, and associates. The study was published in the Journal of Intelligent & Robotic Systems.
Inattentive and hyperactive-impulsive behavior was measured by the number of omission and commission errors. Response time and task completion time contributed to the measure of inattentive and hyperactive-impulsive behavior. Working memory deficits were measured as deviations in the prescribed route.
This figure improved over the course of the study as the tool learned more, indicating that generalization errors were not a serious issue for the tool, the investigators noted.
“Unlike conventional questionnaire-based tests, the robot-assisted test increases the accuracy of ADHD diagnosis by directly reflecting the quality of children’s behavior during the activity game with the robot involved in the action. Since the test obtains behavioral patterns and levels using robotic sensing technologies, it can reliably determine the three key elements of ADHD diagnosis: hyperactivity, inattentive behavior, and working memory,” the investigators wrote. Ultimately, Dr. Choi and associates wrote, the tool could help clinicians diagnose childhood ADHD.
The study was funded by the South Korean Ministry of Trade, Industry, & Energy. No disclosures were reported.
SOURCE: Choi M-T et al. J Intell Robot Syst. 2018 Jun 19. doi: 10.1007/s10846-018-0890-9.
A novel robot-assisted, gamelike test accurately classified ADHD type in elementary school–aged children, according to Mun-Taek Choi, PhD, and associates.
A total of 326 children in the third and fourth grades were included in the study, 35 of whom had been diagnosed with ADHD and 26 of whom were at risk. For the 10- to 12-minute test, participants followed a robot on a path across a numbered mat while stimuli were shown on a TV with both images and sound, and completed a task at each numbered square, reported Dr. Choi, of Sungkyunkwan University, Suwan, South Korea, and associates. The study was published in the Journal of Intelligent & Robotic Systems.
Inattentive and hyperactive-impulsive behavior was measured by the number of omission and commission errors. Response time and task completion time contributed to the measure of inattentive and hyperactive-impulsive behavior. Working memory deficits were measured as deviations in the prescribed route.
This figure improved over the course of the study as the tool learned more, indicating that generalization errors were not a serious issue for the tool, the investigators noted.
“Unlike conventional questionnaire-based tests, the robot-assisted test increases the accuracy of ADHD diagnosis by directly reflecting the quality of children’s behavior during the activity game with the robot involved in the action. Since the test obtains behavioral patterns and levels using robotic sensing technologies, it can reliably determine the three key elements of ADHD diagnosis: hyperactivity, inattentive behavior, and working memory,” the investigators wrote. Ultimately, Dr. Choi and associates wrote, the tool could help clinicians diagnose childhood ADHD.
The study was funded by the South Korean Ministry of Trade, Industry, & Energy. No disclosures were reported.
SOURCE: Choi M-T et al. J Intell Robot Syst. 2018 Jun 19. doi: 10.1007/s10846-018-0890-9.
FROM THE JOURNAL OF INTELLIGENT & ROBOTIC SYSTEMS
Psychodiagnostic testing services: The elusive quest for clinicians
Assessment psychologists should be colocated in specialty practices
Imagine the clinical care consequences if patients seen in specialty or primary care practices did not have ready access to laboratory, other medical tests, and/or consultative services deemed critical to quickly establishing diagnostic status and the development of an appropriate treatment plan. For instance, what would be the implications if a dentistry practice did not employ a dental hygienist; an otolaryngology group was not staffed with an audiologist; or a gastroenterology practice had no one available for digestive/nutritional consultation support.
Consider a neurologist who suspects that a patient has a potentially life-threatening brain condition, but the patient has to wait months for brain imaging or – even worse – is tasked to find their own provider for this diagnostic test only to be told that the neuroimaging service does not take their insurance and/or there are no available appointments for several months.
Situations of this kind would not be – and should not be – tolerated by medical professionals or their patients.
A common “real-world” scenario: After evaluation, a psychiatrist needs clarification regarding a possible subtle psychotic process, or, in another instance, suspects that there is an early degenerative cognitive change underlying recent changes in mood and personality. However, the psychiatrist has no dependable access to an assessment psychologist to assist in cases of this kind.
Patients are frequently told by psychiatrists and other physicians that they should have psychodiagnostic testing to arrive at a clearer picture of their clinical status and treatment needs. However, most medical practices, in particular, psychiatry, pediatrics, neurology, and neurosurgery, who see substantial numbers of patients who could benefit from testing, do not employ psychologists. When they do, many do not possess the requisite assessment skills to address the reason(s) for referral.
If the patient needing testing services is fortunate enough, he/she is referred to a well-trained psychologist within commuting distance who takes the patient’s insurance and is able to set up a timely appointment – an unlikely set of circumstances in today’s health care environment.
Some state psychological associations allow for a “matching service” of sorts in the form of announcements in the organization’s listserv, which reviews the referral and includes a back channel for psychologists to contact the patient regarding their availability for testing.
Over the past 2 decades, significant advancements have been made in the integration of primary and mental health care. Those need to continue to include colocating assessment psychologists in medical specialty practices, such as psychiatry, which make frequent referrals for psychodiagnostic testing or would like to but have no place to turn.
Dr. Pollak is affiliated with the Seacoast Mental Health Center in Portsmouth, N.H.
Assessment psychologists should be colocated in specialty practices
Assessment psychologists should be colocated in specialty practices
Imagine the clinical care consequences if patients seen in specialty or primary care practices did not have ready access to laboratory, other medical tests, and/or consultative services deemed critical to quickly establishing diagnostic status and the development of an appropriate treatment plan. For instance, what would be the implications if a dentistry practice did not employ a dental hygienist; an otolaryngology group was not staffed with an audiologist; or a gastroenterology practice had no one available for digestive/nutritional consultation support.
Consider a neurologist who suspects that a patient has a potentially life-threatening brain condition, but the patient has to wait months for brain imaging or – even worse – is tasked to find their own provider for this diagnostic test only to be told that the neuroimaging service does not take their insurance and/or there are no available appointments for several months.
Situations of this kind would not be – and should not be – tolerated by medical professionals or their patients.
A common “real-world” scenario: After evaluation, a psychiatrist needs clarification regarding a possible subtle psychotic process, or, in another instance, suspects that there is an early degenerative cognitive change underlying recent changes in mood and personality. However, the psychiatrist has no dependable access to an assessment psychologist to assist in cases of this kind.
Patients are frequently told by psychiatrists and other physicians that they should have psychodiagnostic testing to arrive at a clearer picture of their clinical status and treatment needs. However, most medical practices, in particular, psychiatry, pediatrics, neurology, and neurosurgery, who see substantial numbers of patients who could benefit from testing, do not employ psychologists. When they do, many do not possess the requisite assessment skills to address the reason(s) for referral.
If the patient needing testing services is fortunate enough, he/she is referred to a well-trained psychologist within commuting distance who takes the patient’s insurance and is able to set up a timely appointment – an unlikely set of circumstances in today’s health care environment.
Some state psychological associations allow for a “matching service” of sorts in the form of announcements in the organization’s listserv, which reviews the referral and includes a back channel for psychologists to contact the patient regarding their availability for testing.
Over the past 2 decades, significant advancements have been made in the integration of primary and mental health care. Those need to continue to include colocating assessment psychologists in medical specialty practices, such as psychiatry, which make frequent referrals for psychodiagnostic testing or would like to but have no place to turn.
Dr. Pollak is affiliated with the Seacoast Mental Health Center in Portsmouth, N.H.
Imagine the clinical care consequences if patients seen in specialty or primary care practices did not have ready access to laboratory, other medical tests, and/or consultative services deemed critical to quickly establishing diagnostic status and the development of an appropriate treatment plan. For instance, what would be the implications if a dentistry practice did not employ a dental hygienist; an otolaryngology group was not staffed with an audiologist; or a gastroenterology practice had no one available for digestive/nutritional consultation support.
Consider a neurologist who suspects that a patient has a potentially life-threatening brain condition, but the patient has to wait months for brain imaging or – even worse – is tasked to find their own provider for this diagnostic test only to be told that the neuroimaging service does not take their insurance and/or there are no available appointments for several months.
Situations of this kind would not be – and should not be – tolerated by medical professionals or their patients.
A common “real-world” scenario: After evaluation, a psychiatrist needs clarification regarding a possible subtle psychotic process, or, in another instance, suspects that there is an early degenerative cognitive change underlying recent changes in mood and personality. However, the psychiatrist has no dependable access to an assessment psychologist to assist in cases of this kind.
Patients are frequently told by psychiatrists and other physicians that they should have psychodiagnostic testing to arrive at a clearer picture of their clinical status and treatment needs. However, most medical practices, in particular, psychiatry, pediatrics, neurology, and neurosurgery, who see substantial numbers of patients who could benefit from testing, do not employ psychologists. When they do, many do not possess the requisite assessment skills to address the reason(s) for referral.
If the patient needing testing services is fortunate enough, he/she is referred to a well-trained psychologist within commuting distance who takes the patient’s insurance and is able to set up a timely appointment – an unlikely set of circumstances in today’s health care environment.
Some state psychological associations allow for a “matching service” of sorts in the form of announcements in the organization’s listserv, which reviews the referral and includes a back channel for psychologists to contact the patient regarding their availability for testing.
Over the past 2 decades, significant advancements have been made in the integration of primary and mental health care. Those need to continue to include colocating assessment psychologists in medical specialty practices, such as psychiatry, which make frequent referrals for psychodiagnostic testing or would like to but have no place to turn.
Dr. Pollak is affiliated with the Seacoast Mental Health Center in Portsmouth, N.H.
DNA methylation changes: An early biomarker for methotrexate response?
An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.
“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.
The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.
After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.
The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”
The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411
An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.
“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.
The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.
After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.
The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”
The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411
An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.
“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.
The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.
After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.
The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”
The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411
FROM RHEUMATOLOGY
Research on pediatric firearms deaths is underfunded
new research has found.
For the period 2008-2017, an average of $88 million per year was granted to study motor vehicle crashes, the leading cause of death in this age group. Cancer, the third leading cause of mortality, received on average $335 million per year. However, research into mortality from firearms, the second leading cause of death in this age group, received $12 million total during the entire research period across a total of 32 research grants.
This translates to $26,136 in research funding per death for the 33,577 deaths of children and adolescents in motor vehicle crashes from 2008-2017, $195,508 per death from cancer (17,111 deaths recorded), and just $597 per death from firearm injury (20,719 deaths recorded).
Pediatric firearm injury prevention “is substantially underfunded in relation to the magnitude of the public health problem,” Rebecca Cunningham, MD, from the University of Michigan, Ann Arbor, and colleagues wrote in the October 2019 issue of Health Affairs.
“According to our analysis, federal funding for this leading cause of pediatric mortality is 3.3 percent of what would be needed for it to be commensurate with the funding for other common causes of pediatric death,” the authors continued.
Dr. Cunningham and colleagues said that the “lack of an evidence base for firearm safety prevention has likely contributed to the lack of progress on, and recent increase in, firearm deaths among children and adolescents since 2013.”
They did note that there was an increase in federal research funding following the shooting in Newtown, Conn., with an increase from $136,224 in 2012 to $4.5 million in 2017, but it clearly is not enough.
“Our analysis, using other major diseases and the country’s history of federal funding as a guide, demonstrates that approximately $37 million per year over the next decade is needed to realize a reduction in pediatric firearm mortality that is comparable to that observed for other pediatric causes of death,” the authors state.
The group also suggests the development of a group similar to the National Highway Traffic Safety Administration that is focused specifically on firearm safety that could “begin to address the large gaps in foundational epidemiological and multidisciplinary behavioral research that the nation needs. It could have a transformational impact on the reduction of firearm injuries among children and adolescents parallel to what has been seen for other major causes of pediatric death in the U.S.”
SOURCE: Cunningham R et al. Health Affairs. 2019. doi: 10.1377/hlthaff.2019.00476.
new research has found.
For the period 2008-2017, an average of $88 million per year was granted to study motor vehicle crashes, the leading cause of death in this age group. Cancer, the third leading cause of mortality, received on average $335 million per year. However, research into mortality from firearms, the second leading cause of death in this age group, received $12 million total during the entire research period across a total of 32 research grants.
This translates to $26,136 in research funding per death for the 33,577 deaths of children and adolescents in motor vehicle crashes from 2008-2017, $195,508 per death from cancer (17,111 deaths recorded), and just $597 per death from firearm injury (20,719 deaths recorded).
Pediatric firearm injury prevention “is substantially underfunded in relation to the magnitude of the public health problem,” Rebecca Cunningham, MD, from the University of Michigan, Ann Arbor, and colleagues wrote in the October 2019 issue of Health Affairs.
“According to our analysis, federal funding for this leading cause of pediatric mortality is 3.3 percent of what would be needed for it to be commensurate with the funding for other common causes of pediatric death,” the authors continued.
Dr. Cunningham and colleagues said that the “lack of an evidence base for firearm safety prevention has likely contributed to the lack of progress on, and recent increase in, firearm deaths among children and adolescents since 2013.”
They did note that there was an increase in federal research funding following the shooting in Newtown, Conn., with an increase from $136,224 in 2012 to $4.5 million in 2017, but it clearly is not enough.
“Our analysis, using other major diseases and the country’s history of federal funding as a guide, demonstrates that approximately $37 million per year over the next decade is needed to realize a reduction in pediatric firearm mortality that is comparable to that observed for other pediatric causes of death,” the authors state.
The group also suggests the development of a group similar to the National Highway Traffic Safety Administration that is focused specifically on firearm safety that could “begin to address the large gaps in foundational epidemiological and multidisciplinary behavioral research that the nation needs. It could have a transformational impact on the reduction of firearm injuries among children and adolescents parallel to what has been seen for other major causes of pediatric death in the U.S.”
SOURCE: Cunningham R et al. Health Affairs. 2019. doi: 10.1377/hlthaff.2019.00476.
new research has found.
For the period 2008-2017, an average of $88 million per year was granted to study motor vehicle crashes, the leading cause of death in this age group. Cancer, the third leading cause of mortality, received on average $335 million per year. However, research into mortality from firearms, the second leading cause of death in this age group, received $12 million total during the entire research period across a total of 32 research grants.
This translates to $26,136 in research funding per death for the 33,577 deaths of children and adolescents in motor vehicle crashes from 2008-2017, $195,508 per death from cancer (17,111 deaths recorded), and just $597 per death from firearm injury (20,719 deaths recorded).
Pediatric firearm injury prevention “is substantially underfunded in relation to the magnitude of the public health problem,” Rebecca Cunningham, MD, from the University of Michigan, Ann Arbor, and colleagues wrote in the October 2019 issue of Health Affairs.
“According to our analysis, federal funding for this leading cause of pediatric mortality is 3.3 percent of what would be needed for it to be commensurate with the funding for other common causes of pediatric death,” the authors continued.
Dr. Cunningham and colleagues said that the “lack of an evidence base for firearm safety prevention has likely contributed to the lack of progress on, and recent increase in, firearm deaths among children and adolescents since 2013.”
They did note that there was an increase in federal research funding following the shooting in Newtown, Conn., with an increase from $136,224 in 2012 to $4.5 million in 2017, but it clearly is not enough.
“Our analysis, using other major diseases and the country’s history of federal funding as a guide, demonstrates that approximately $37 million per year over the next decade is needed to realize a reduction in pediatric firearm mortality that is comparable to that observed for other pediatric causes of death,” the authors state.
The group also suggests the development of a group similar to the National Highway Traffic Safety Administration that is focused specifically on firearm safety that could “begin to address the large gaps in foundational epidemiological and multidisciplinary behavioral research that the nation needs. It could have a transformational impact on the reduction of firearm injuries among children and adolescents parallel to what has been seen for other major causes of pediatric death in the U.S.”
SOURCE: Cunningham R et al. Health Affairs. 2019. doi: 10.1377/hlthaff.2019.00476.
FROM HEALTH AFFAIRS
New mechanisms, therapies for acne considered
SEATTLE – It used to be thought that acne begins with microcomedones, which go on to develop either inflammatory lesions or noninflammatory lesions, but more recent evidence has changed that perception, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital, Detroit.
Dr. Stein Gold said at the annual Coastal Dermatology Symposium. “All acne is inflammation acne,” and inflammation also persists, she added. Biopsies of scarred lesions, once considered postinflammatory, also have revealed persistent inflammation, she noted.
One study found that persistent scars can evolve from closed comedones, papules, and pustules, but the most common was a papule that turned into a postinflammatory lesion (J Drugs Dermatol 2017 Jun 1;16[6]:566-72). “So when patients come in and they have these red spots on their face, it’s not over. There’s still time to be aggressive because those inflammatory lesions are more likely to lead to scars than anything else,” Dr. Stein Gold said. “And we also know that papules that develop into scars do so because they’re there for a longer period of time. Those that develop scars are present about 10.5 days, compared with 6.6 days for those that don’t develop into scars.”
She went on to review some of the new treatments for acne that can be brought to bear in such cases. These include developments with topical retinoids that are aimed at improving delivery and reducing skin irritation.
A new topical retinoid, trifarotene cream, 0.005%, showed efficacy and tolerability for both the face and trunk in a recent phase 3 trial of patients with moderate facial and truncal acne and was recently approved for patients aged 9 years and older. In the study, about 30%-40% of people aged 9 years and older treated with once-daily trifarotene cream (Aklief) achieved clear or almost-clear status of the face at 12 weeks, vs. about 20% and 26%, of those on the vehicle cream (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9).
The drug can also treat papules and pustules, nearly as well as it treats blackheads and whiteheads, according to Dr. Stein Gold. Like other retinoids, it produces some redness and scaling and rather than letting these adverse events discourage patients, she leans in. “I tell patients they’re going to have some sloughing of the skin the first 2 weeks. I tell them that people pay money for that. It’s called a chemical peel,” said Dr. Stein Gold, noting that patients respond well to this information.
If patients find the treatments too irritating, she advises them to avoid applying it to wet skin. They can also apply it every other night, or even less frequently, and then work up to more frequent use, she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.
Tazarotene is another topical retinoid that can be very irritating. A new lotion formulation of tazarotene 0.045% contains a lower dose than the 0.1% typically used in creams, and has similar efficacy but reduced irritation, Dr. Stein Gold said. In August, the manufacturer submitted an application for approval with the Food and Drug Administration for treatment of acne.
Dr. Stein Gold also talked about using retinoids to minimize scarring, referring to a study of patients with moderate and severe facial acne, and atrophic acne scars, comparing adapalene 0.3% plus benzoyl peroxide 2.5% gel on one side of the face and vehicle on the other side of the face for 24 weeks, followed by application of the active treatment to both sides of the face for 24 weeks. Treatment was associated with a reduction of atrophic acne scars at 24 weeks, which was maintained for up to 48 weeks (Am J Clin Dermatol. 2019 Oct[5];20:725-32).
“We can now say to patients, ‘Not only can I help you with your acne, but I can potentially even improve your atrophic scarring,’ ” she said.
Finally, she discussed clascoterone, a novel androgen receptor antagonist, which inhibits sebum production and prevents colonization by Cutibacterium acnes (formerly called Propionibacterium acnes) and subsequent inflammation. “It does a lot of good things in terms of the pathogenesis of acne, but more importantly, it is one of the first drugs that topically has been shown to decrease the production of sebum,” Dr. Stein Gold said. A 1% cream formulation is being studied for acne.
Dr. Stein Gold is a consultant, investigator, and/or speaker for Galderma, Ortho Derm, Sol Gel, Foamix, Cassiopea, and Almirall.
This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – It used to be thought that acne begins with microcomedones, which go on to develop either inflammatory lesions or noninflammatory lesions, but more recent evidence has changed that perception, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital, Detroit.
Dr. Stein Gold said at the annual Coastal Dermatology Symposium. “All acne is inflammation acne,” and inflammation also persists, she added. Biopsies of scarred lesions, once considered postinflammatory, also have revealed persistent inflammation, she noted.
One study found that persistent scars can evolve from closed comedones, papules, and pustules, but the most common was a papule that turned into a postinflammatory lesion (J Drugs Dermatol 2017 Jun 1;16[6]:566-72). “So when patients come in and they have these red spots on their face, it’s not over. There’s still time to be aggressive because those inflammatory lesions are more likely to lead to scars than anything else,” Dr. Stein Gold said. “And we also know that papules that develop into scars do so because they’re there for a longer period of time. Those that develop scars are present about 10.5 days, compared with 6.6 days for those that don’t develop into scars.”
She went on to review some of the new treatments for acne that can be brought to bear in such cases. These include developments with topical retinoids that are aimed at improving delivery and reducing skin irritation.
A new topical retinoid, trifarotene cream, 0.005%, showed efficacy and tolerability for both the face and trunk in a recent phase 3 trial of patients with moderate facial and truncal acne and was recently approved for patients aged 9 years and older. In the study, about 30%-40% of people aged 9 years and older treated with once-daily trifarotene cream (Aklief) achieved clear or almost-clear status of the face at 12 weeks, vs. about 20% and 26%, of those on the vehicle cream (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9).
The drug can also treat papules and pustules, nearly as well as it treats blackheads and whiteheads, according to Dr. Stein Gold. Like other retinoids, it produces some redness and scaling and rather than letting these adverse events discourage patients, she leans in. “I tell patients they’re going to have some sloughing of the skin the first 2 weeks. I tell them that people pay money for that. It’s called a chemical peel,” said Dr. Stein Gold, noting that patients respond well to this information.
If patients find the treatments too irritating, she advises them to avoid applying it to wet skin. They can also apply it every other night, or even less frequently, and then work up to more frequent use, she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.
Tazarotene is another topical retinoid that can be very irritating. A new lotion formulation of tazarotene 0.045% contains a lower dose than the 0.1% typically used in creams, and has similar efficacy but reduced irritation, Dr. Stein Gold said. In August, the manufacturer submitted an application for approval with the Food and Drug Administration for treatment of acne.
Dr. Stein Gold also talked about using retinoids to minimize scarring, referring to a study of patients with moderate and severe facial acne, and atrophic acne scars, comparing adapalene 0.3% plus benzoyl peroxide 2.5% gel on one side of the face and vehicle on the other side of the face for 24 weeks, followed by application of the active treatment to both sides of the face for 24 weeks. Treatment was associated with a reduction of atrophic acne scars at 24 weeks, which was maintained for up to 48 weeks (Am J Clin Dermatol. 2019 Oct[5];20:725-32).
“We can now say to patients, ‘Not only can I help you with your acne, but I can potentially even improve your atrophic scarring,’ ” she said.
Finally, she discussed clascoterone, a novel androgen receptor antagonist, which inhibits sebum production and prevents colonization by Cutibacterium acnes (formerly called Propionibacterium acnes) and subsequent inflammation. “It does a lot of good things in terms of the pathogenesis of acne, but more importantly, it is one of the first drugs that topically has been shown to decrease the production of sebum,” Dr. Stein Gold said. A 1% cream formulation is being studied for acne.
Dr. Stein Gold is a consultant, investigator, and/or speaker for Galderma, Ortho Derm, Sol Gel, Foamix, Cassiopea, and Almirall.
This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – It used to be thought that acne begins with microcomedones, which go on to develop either inflammatory lesions or noninflammatory lesions, but more recent evidence has changed that perception, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital, Detroit.
Dr. Stein Gold said at the annual Coastal Dermatology Symposium. “All acne is inflammation acne,” and inflammation also persists, she added. Biopsies of scarred lesions, once considered postinflammatory, also have revealed persistent inflammation, she noted.
One study found that persistent scars can evolve from closed comedones, papules, and pustules, but the most common was a papule that turned into a postinflammatory lesion (J Drugs Dermatol 2017 Jun 1;16[6]:566-72). “So when patients come in and they have these red spots on their face, it’s not over. There’s still time to be aggressive because those inflammatory lesions are more likely to lead to scars than anything else,” Dr. Stein Gold said. “And we also know that papules that develop into scars do so because they’re there for a longer period of time. Those that develop scars are present about 10.5 days, compared with 6.6 days for those that don’t develop into scars.”
She went on to review some of the new treatments for acne that can be brought to bear in such cases. These include developments with topical retinoids that are aimed at improving delivery and reducing skin irritation.
A new topical retinoid, trifarotene cream, 0.005%, showed efficacy and tolerability for both the face and trunk in a recent phase 3 trial of patients with moderate facial and truncal acne and was recently approved for patients aged 9 years and older. In the study, about 30%-40% of people aged 9 years and older treated with once-daily trifarotene cream (Aklief) achieved clear or almost-clear status of the face at 12 weeks, vs. about 20% and 26%, of those on the vehicle cream (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9).
The drug can also treat papules and pustules, nearly as well as it treats blackheads and whiteheads, according to Dr. Stein Gold. Like other retinoids, it produces some redness and scaling and rather than letting these adverse events discourage patients, she leans in. “I tell patients they’re going to have some sloughing of the skin the first 2 weeks. I tell them that people pay money for that. It’s called a chemical peel,” said Dr. Stein Gold, noting that patients respond well to this information.
If patients find the treatments too irritating, she advises them to avoid applying it to wet skin. They can also apply it every other night, or even less frequently, and then work up to more frequent use, she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.
Tazarotene is another topical retinoid that can be very irritating. A new lotion formulation of tazarotene 0.045% contains a lower dose than the 0.1% typically used in creams, and has similar efficacy but reduced irritation, Dr. Stein Gold said. In August, the manufacturer submitted an application for approval with the Food and Drug Administration for treatment of acne.
Dr. Stein Gold also talked about using retinoids to minimize scarring, referring to a study of patients with moderate and severe facial acne, and atrophic acne scars, comparing adapalene 0.3% plus benzoyl peroxide 2.5% gel on one side of the face and vehicle on the other side of the face for 24 weeks, followed by application of the active treatment to both sides of the face for 24 weeks. Treatment was associated with a reduction of atrophic acne scars at 24 weeks, which was maintained for up to 48 weeks (Am J Clin Dermatol. 2019 Oct[5];20:725-32).
“We can now say to patients, ‘Not only can I help you with your acne, but I can potentially even improve your atrophic scarring,’ ” she said.
Finally, she discussed clascoterone, a novel androgen receptor antagonist, which inhibits sebum production and prevents colonization by Cutibacterium acnes (formerly called Propionibacterium acnes) and subsequent inflammation. “It does a lot of good things in terms of the pathogenesis of acne, but more importantly, it is one of the first drugs that topically has been shown to decrease the production of sebum,” Dr. Stein Gold said. A 1% cream formulation is being studied for acne.
Dr. Stein Gold is a consultant, investigator, and/or speaker for Galderma, Ortho Derm, Sol Gel, Foamix, Cassiopea, and Almirall.
This publication and Global Academy for Medical Education are owned by the same parent company.
EXPERT ANALYSIS FROM COASTAL DERM
Take drug, patient-level factors into account for when to end antiresorptive therapy
LAS VEGAS – according to an overview presented by Marcy B. Bolster, MD.
Recently published studies may help guide decisions about initiating and discontinuing treatment with bisphosphonates or denosumab (Prolia), the antiresorptive therapies. Understanding the ideal duration of bisphosphonate drug holidays “is a work in progress,” Dr. Bolster, from Harvard Medical School in Boston, said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
No holiday with denosumab
Data indicate that twice yearly denosumab remains safe at 10 years, but studies have found a rapid loss of bone mineral density and an increased risk for vertebral fractures after treatment is discontinued (J Bone Miner Res. 2018 Feb;33[2]:190-8).
“Therefore, it is not appropriate for denosumab to be utilized with a drug holiday. If a patient is placed on denosumab, then consideration needs to be given for what to follow the course of denosumab,” Dr. Bolster said. “It is important to review with our patients the essential scheduled dosing of every 6 months, that the patient should not miss doses, and that we are not going to be able to initiate a drug holiday without starting another medicine.”
Patients likely to require hospitalization may not be good candidates for denosumab therapy because they may not be able to adhere to the dosing regimen, she said.
Denosumab vs. bisphosphonates: Real-world data
Trials have found greater increases in bone mineral density with denosumab, compared with the bisphosphonate drug alendronate, but that finding does not necessarily equate with reduced fracture risk, Dr. Bolster said. A recent population-based study examined fracture risk in approximately 92,000 people over age 50 years. Most were women, and their mean age was 71 years (JAMA Netw Open. 2019 Apr 5;2[4]:e192416).
The researchers compared the incidence of hospitalization for hip fracture among new denosumab users and new alendronate users during the 3 years after starting treatment. At 3 years, hip fractures occurred in 3.7% of the denosumab group and in 3.1% of the alendronate group. The rate of any fracture was 9% for each group. Although the study design had limitations, the analysis found “no difference between denosumab and alendronate in terms of fracture-risk reduction,” Dr. Bolster said. “Both agents are good agents.”
A recent meta-analysis compared fracture risk with denosumab and any bisphosphonate treatment using data from 10 trials that included more than 5,000 patients (J Clin Endocrinol Metab. 2019 May 1;104[5]:1753-65).
At 12 and 24 months, denosumab produced greater increases in bone mineral density at the spine, hip, and femoral neck. “In fact, there was a greater increase in bone density seen in those on denosumab who had had prior bisphosphonate use,” Dr. Bolster said. In 9 out of 10 trials, however, fracture rate did not differ between patients who received denosumab or any bisphosphonate at 12 or 24 months.
Bisphosphonate drug holidays
An increased risk of atypical femoral fracture with long-term bisphosphonate therapy has driven research on the effects of bisphosphonate drug holidays. “When we start a drug holiday, it requires continued close monitoring of the patient’s risk factors,” as well as monitoring whether a new fracture occurs during the holiday, Dr. Bolster said.
“We have very little data to guide the duration of a drug holiday,” she said. One study examined changes in bone density and bone turnover markers during a drug holiday after treatment with oral alendronate or intravenous zoledronic acid (J Bone Miner Res. 2019 May;34[5]:810-6).
The investigators conducted a post hoc analysis of data from the FLEX and HORIZON trials. Although alendronate was used for a longer duration, compared with zoledronic acid (5 years vs. 3 years), alendronate had a more rapid offset of drug effect after 3 years. The difference may relate to compliance rates with oral therapy during the treatment period, Dr. Bolster said.
The study did not examine fracture rates, which is the outcome that ultimately matters at the end of the day, she said.
Data suggest that bisphosphonate holidays are associated with increased risk of hip fracture. An analysis of Medicare data by Curtis et al. found that “hip fracture rates were lowest among those who remained on bisphosphonates,” Dr. Bolster said. Hip fracture rates increased with the length of the drug holiday, and a drug holiday of between 2 and 3 years was associated with 39% increased risk. The analysis included data from more than 156,000 women, about 40% of whom stopped bisphosphonates for more than 6 months. A total of 3,745 hip fractures occurred during follow-up.
Individualize treatment
“Duration of therapy should be individualized to the patient,” Dr. Bolster said. Physicians should assess the patient’s risk factors and take into account fragility fractures before and during treatment, bone density, and comorbidities.
“In terms of duration for drug holiday, does the patient now have osteopenia after treatment?” she said. “It is uncommon for bone density to change significantly during treatment, but occasionally we have a patient who goes from osteoporosis to osteopenia.”
The resumption of treatment should be based on established guidelines and individual patient factors, she said. For some postmenopausal woman, estrogen or raloxifene may not be ideal treatments when resuming therapy because these medications may increase cardiovascular or thrombotic risks. Denosumab may not be a good option for some patients because of the limitations surrounding its ability to be discontinued. The anabolic agents teriparatide and abaloparatide “may be good options to consider after a drug holiday, or even to give to patients during the drug holiday,” Dr. Bolster said. “The drug holiday does not have to be a treatment holiday. It really just needs to be an antiresorptive holiday.”
Dr. Bolster owns stock in Johnson & Johnson and is on an advisory board for Gilead.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – according to an overview presented by Marcy B. Bolster, MD.
Recently published studies may help guide decisions about initiating and discontinuing treatment with bisphosphonates or denosumab (Prolia), the antiresorptive therapies. Understanding the ideal duration of bisphosphonate drug holidays “is a work in progress,” Dr. Bolster, from Harvard Medical School in Boston, said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
No holiday with denosumab
Data indicate that twice yearly denosumab remains safe at 10 years, but studies have found a rapid loss of bone mineral density and an increased risk for vertebral fractures after treatment is discontinued (J Bone Miner Res. 2018 Feb;33[2]:190-8).
“Therefore, it is not appropriate for denosumab to be utilized with a drug holiday. If a patient is placed on denosumab, then consideration needs to be given for what to follow the course of denosumab,” Dr. Bolster said. “It is important to review with our patients the essential scheduled dosing of every 6 months, that the patient should not miss doses, and that we are not going to be able to initiate a drug holiday without starting another medicine.”
Patients likely to require hospitalization may not be good candidates for denosumab therapy because they may not be able to adhere to the dosing regimen, she said.
Denosumab vs. bisphosphonates: Real-world data
Trials have found greater increases in bone mineral density with denosumab, compared with the bisphosphonate drug alendronate, but that finding does not necessarily equate with reduced fracture risk, Dr. Bolster said. A recent population-based study examined fracture risk in approximately 92,000 people over age 50 years. Most were women, and their mean age was 71 years (JAMA Netw Open. 2019 Apr 5;2[4]:e192416).
The researchers compared the incidence of hospitalization for hip fracture among new denosumab users and new alendronate users during the 3 years after starting treatment. At 3 years, hip fractures occurred in 3.7% of the denosumab group and in 3.1% of the alendronate group. The rate of any fracture was 9% for each group. Although the study design had limitations, the analysis found “no difference between denosumab and alendronate in terms of fracture-risk reduction,” Dr. Bolster said. “Both agents are good agents.”
A recent meta-analysis compared fracture risk with denosumab and any bisphosphonate treatment using data from 10 trials that included more than 5,000 patients (J Clin Endocrinol Metab. 2019 May 1;104[5]:1753-65).
At 12 and 24 months, denosumab produced greater increases in bone mineral density at the spine, hip, and femoral neck. “In fact, there was a greater increase in bone density seen in those on denosumab who had had prior bisphosphonate use,” Dr. Bolster said. In 9 out of 10 trials, however, fracture rate did not differ between patients who received denosumab or any bisphosphonate at 12 or 24 months.
Bisphosphonate drug holidays
An increased risk of atypical femoral fracture with long-term bisphosphonate therapy has driven research on the effects of bisphosphonate drug holidays. “When we start a drug holiday, it requires continued close monitoring of the patient’s risk factors,” as well as monitoring whether a new fracture occurs during the holiday, Dr. Bolster said.
“We have very little data to guide the duration of a drug holiday,” she said. One study examined changes in bone density and bone turnover markers during a drug holiday after treatment with oral alendronate or intravenous zoledronic acid (J Bone Miner Res. 2019 May;34[5]:810-6).
The investigators conducted a post hoc analysis of data from the FLEX and HORIZON trials. Although alendronate was used for a longer duration, compared with zoledronic acid (5 years vs. 3 years), alendronate had a more rapid offset of drug effect after 3 years. The difference may relate to compliance rates with oral therapy during the treatment period, Dr. Bolster said.
The study did not examine fracture rates, which is the outcome that ultimately matters at the end of the day, she said.
Data suggest that bisphosphonate holidays are associated with increased risk of hip fracture. An analysis of Medicare data by Curtis et al. found that “hip fracture rates were lowest among those who remained on bisphosphonates,” Dr. Bolster said. Hip fracture rates increased with the length of the drug holiday, and a drug holiday of between 2 and 3 years was associated with 39% increased risk. The analysis included data from more than 156,000 women, about 40% of whom stopped bisphosphonates for more than 6 months. A total of 3,745 hip fractures occurred during follow-up.
Individualize treatment
“Duration of therapy should be individualized to the patient,” Dr. Bolster said. Physicians should assess the patient’s risk factors and take into account fragility fractures before and during treatment, bone density, and comorbidities.
“In terms of duration for drug holiday, does the patient now have osteopenia after treatment?” she said. “It is uncommon for bone density to change significantly during treatment, but occasionally we have a patient who goes from osteoporosis to osteopenia.”
The resumption of treatment should be based on established guidelines and individual patient factors, she said. For some postmenopausal woman, estrogen or raloxifene may not be ideal treatments when resuming therapy because these medications may increase cardiovascular or thrombotic risks. Denosumab may not be a good option for some patients because of the limitations surrounding its ability to be discontinued. The anabolic agents teriparatide and abaloparatide “may be good options to consider after a drug holiday, or even to give to patients during the drug holiday,” Dr. Bolster said. “The drug holiday does not have to be a treatment holiday. It really just needs to be an antiresorptive holiday.”
Dr. Bolster owns stock in Johnson & Johnson and is on an advisory board for Gilead.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – according to an overview presented by Marcy B. Bolster, MD.
Recently published studies may help guide decisions about initiating and discontinuing treatment with bisphosphonates or denosumab (Prolia), the antiresorptive therapies. Understanding the ideal duration of bisphosphonate drug holidays “is a work in progress,” Dr. Bolster, from Harvard Medical School in Boston, said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
No holiday with denosumab
Data indicate that twice yearly denosumab remains safe at 10 years, but studies have found a rapid loss of bone mineral density and an increased risk for vertebral fractures after treatment is discontinued (J Bone Miner Res. 2018 Feb;33[2]:190-8).
“Therefore, it is not appropriate for denosumab to be utilized with a drug holiday. If a patient is placed on denosumab, then consideration needs to be given for what to follow the course of denosumab,” Dr. Bolster said. “It is important to review with our patients the essential scheduled dosing of every 6 months, that the patient should not miss doses, and that we are not going to be able to initiate a drug holiday without starting another medicine.”
Patients likely to require hospitalization may not be good candidates for denosumab therapy because they may not be able to adhere to the dosing regimen, she said.
Denosumab vs. bisphosphonates: Real-world data
Trials have found greater increases in bone mineral density with denosumab, compared with the bisphosphonate drug alendronate, but that finding does not necessarily equate with reduced fracture risk, Dr. Bolster said. A recent population-based study examined fracture risk in approximately 92,000 people over age 50 years. Most were women, and their mean age was 71 years (JAMA Netw Open. 2019 Apr 5;2[4]:e192416).
The researchers compared the incidence of hospitalization for hip fracture among new denosumab users and new alendronate users during the 3 years after starting treatment. At 3 years, hip fractures occurred in 3.7% of the denosumab group and in 3.1% of the alendronate group. The rate of any fracture was 9% for each group. Although the study design had limitations, the analysis found “no difference between denosumab and alendronate in terms of fracture-risk reduction,” Dr. Bolster said. “Both agents are good agents.”
A recent meta-analysis compared fracture risk with denosumab and any bisphosphonate treatment using data from 10 trials that included more than 5,000 patients (J Clin Endocrinol Metab. 2019 May 1;104[5]:1753-65).
At 12 and 24 months, denosumab produced greater increases in bone mineral density at the spine, hip, and femoral neck. “In fact, there was a greater increase in bone density seen in those on denosumab who had had prior bisphosphonate use,” Dr. Bolster said. In 9 out of 10 trials, however, fracture rate did not differ between patients who received denosumab or any bisphosphonate at 12 or 24 months.
Bisphosphonate drug holidays
An increased risk of atypical femoral fracture with long-term bisphosphonate therapy has driven research on the effects of bisphosphonate drug holidays. “When we start a drug holiday, it requires continued close monitoring of the patient’s risk factors,” as well as monitoring whether a new fracture occurs during the holiday, Dr. Bolster said.
“We have very little data to guide the duration of a drug holiday,” she said. One study examined changes in bone density and bone turnover markers during a drug holiday after treatment with oral alendronate or intravenous zoledronic acid (J Bone Miner Res. 2019 May;34[5]:810-6).
The investigators conducted a post hoc analysis of data from the FLEX and HORIZON trials. Although alendronate was used for a longer duration, compared with zoledronic acid (5 years vs. 3 years), alendronate had a more rapid offset of drug effect after 3 years. The difference may relate to compliance rates with oral therapy during the treatment period, Dr. Bolster said.
The study did not examine fracture rates, which is the outcome that ultimately matters at the end of the day, she said.
Data suggest that bisphosphonate holidays are associated with increased risk of hip fracture. An analysis of Medicare data by Curtis et al. found that “hip fracture rates were lowest among those who remained on bisphosphonates,” Dr. Bolster said. Hip fracture rates increased with the length of the drug holiday, and a drug holiday of between 2 and 3 years was associated with 39% increased risk. The analysis included data from more than 156,000 women, about 40% of whom stopped bisphosphonates for more than 6 months. A total of 3,745 hip fractures occurred during follow-up.
Individualize treatment
“Duration of therapy should be individualized to the patient,” Dr. Bolster said. Physicians should assess the patient’s risk factors and take into account fragility fractures before and during treatment, bone density, and comorbidities.
“In terms of duration for drug holiday, does the patient now have osteopenia after treatment?” she said. “It is uncommon for bone density to change significantly during treatment, but occasionally we have a patient who goes from osteoporosis to osteopenia.”
The resumption of treatment should be based on established guidelines and individual patient factors, she said. For some postmenopausal woman, estrogen or raloxifene may not be ideal treatments when resuming therapy because these medications may increase cardiovascular or thrombotic risks. Denosumab may not be a good option for some patients because of the limitations surrounding its ability to be discontinued. The anabolic agents teriparatide and abaloparatide “may be good options to consider after a drug holiday, or even to give to patients during the drug holiday,” Dr. Bolster said. “The drug holiday does not have to be a treatment holiday. It really just needs to be an antiresorptive holiday.”
Dr. Bolster owns stock in Johnson & Johnson and is on an advisory board for Gilead.
Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM PRD 2019