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AAP renews public health approach to gun injury prevention
ORLANDO – The American Academy of Pediatrics created the Gun Safety and Injury Prevention Research Initiative to study and implement gun safety interventions to prevent homicide, suicide and unintentional injuries caused by firearms.
In an interview at the annual meeting of the American Academy of Pediatrics, Colleen A. Kraft, MD, FAAP, current AAP president, explained how AAP has renewed its efforts to protect children from firearm injuries. Black children are more likely to die in a homicide, while white children are more likely to die in a suicide through use of a firearm, Dr. Kraft said. The AAP seeks to find a nonpolitical way to discuss gun safety “with a lens on children and a lens on safety,” she said.
“What we are looking to do is to bring together partners who have the research expertise in gun safety and injury prevention, find out what we know, decide what we don’t know yet, and begin to bring together focus groups of parents and families and legislators and doctors, and people to talk about … gun safety in a way that resonates with everyone,” Dr. Kraft said.
Visit AAP’s website for more information on the Gun Safety and Injury Prevention Research Initiative.
Dr. Kraft reports no relevant conflicts of interest.
ORLANDO – The American Academy of Pediatrics created the Gun Safety and Injury Prevention Research Initiative to study and implement gun safety interventions to prevent homicide, suicide and unintentional injuries caused by firearms.
In an interview at the annual meeting of the American Academy of Pediatrics, Colleen A. Kraft, MD, FAAP, current AAP president, explained how AAP has renewed its efforts to protect children from firearm injuries. Black children are more likely to die in a homicide, while white children are more likely to die in a suicide through use of a firearm, Dr. Kraft said. The AAP seeks to find a nonpolitical way to discuss gun safety “with a lens on children and a lens on safety,” she said.
“What we are looking to do is to bring together partners who have the research expertise in gun safety and injury prevention, find out what we know, decide what we don’t know yet, and begin to bring together focus groups of parents and families and legislators and doctors, and people to talk about … gun safety in a way that resonates with everyone,” Dr. Kraft said.
Visit AAP’s website for more information on the Gun Safety and Injury Prevention Research Initiative.
Dr. Kraft reports no relevant conflicts of interest.
ORLANDO – The American Academy of Pediatrics created the Gun Safety and Injury Prevention Research Initiative to study and implement gun safety interventions to prevent homicide, suicide and unintentional injuries caused by firearms.
In an interview at the annual meeting of the American Academy of Pediatrics, Colleen A. Kraft, MD, FAAP, current AAP president, explained how AAP has renewed its efforts to protect children from firearm injuries. Black children are more likely to die in a homicide, while white children are more likely to die in a suicide through use of a firearm, Dr. Kraft said. The AAP seeks to find a nonpolitical way to discuss gun safety “with a lens on children and a lens on safety,” she said.
“What we are looking to do is to bring together partners who have the research expertise in gun safety and injury prevention, find out what we know, decide what we don’t know yet, and begin to bring together focus groups of parents and families and legislators and doctors, and people to talk about … gun safety in a way that resonates with everyone,” Dr. Kraft said.
Visit AAP’s website for more information on the Gun Safety and Injury Prevention Research Initiative.
Dr. Kraft reports no relevant conflicts of interest.
REPORTING FROM AAP 2018
Triggers May Guide Treatment of New Daily Persistent Headache
Aggressive initial therapy is appropriate because the disorder becomes increasingly refractory with time.
ASHEVILLE, NC—New daily persistent headache is rare and difficult to treat. Although neurologists may be tempted to try a series of treatments until the patient improves, therapeutic success is more likely if the neurologist can identify a triggering event, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. Elements of the patient’s history or clinical examination also can guide treatment, he added at the Eighth Annual Scientific Meeting of the Southern Headache Society.
Patients Remember the Onset
New daily persistent headache was first described in 1986, and few researchers have studied it. It is a persistent headache with a clearly remembered onset. “Most [patients] can name the date it began or at least the month,” said Dr. Rozen. The headache becomes unremitting within 24 hours and must be present for longer than three months, according to the current diagnostic criteria. Patients may have a remitting form, a relapsing-remitting form, or a refractory form of the headache. The age of onset “can be as early as in the mid to late teens or early 20s, especially in the female population,” said Dr. Rozen. Age of onset also depends on the triggering event.
The pain typically is bilateral and moderate to severe. Although many patients may present with a tension-type headache, more than 60% have migrainous symptoms such as nausea, photophobia, or phonophobia, said Dr. Rozen.
The disorder is more common among women than among men. Between 10% and 13% of patients who present to headache clinics have new daily persistent headache, said Dr. Rozen. “It is either becoming more prevalent in the office, or we are better at recognizing it.”
Comparing Effects on the Genders
For a study published in 2016, Dr. Rozen examined 97 patients (65 women) with new daily persistent headache. Approximately 53% of patients could not identify a triggering event for their headache, which makes treatment “much more difficult,” said Dr. Rozen. Although the mean age of onset was younger in women (32.4) than men (35.8), the age of onset was the same between genders when Dr. Rozen examined for individual triggers.
The frequency of individual triggering events also was the same between genders, and these results suggest that each trigger may be associated with a discrete pathogenesis. Triggers included infection or flulike illness (22%), stressful life event (9%), surgery (9%), and other (7%). All patients who had identified surgery as a trigger had been intubated, and Dr. Rozen hypothesized that their headaches were cervicogenic. The younger patients who had undergone surgery were hypermobile, and the older patients had neck arthritis as predisposing risk factors for neck irritation with intubation.
A Somatoform Disorder?
The stubbornly refractory nature of this disorder has aroused the suspicion that it may be somatoform. In 2017, Uniyal and colleagues found that somatization, generalized anxiety disorder, depression, and catastrophization were more common in patients with new daily persistent headache, compared with patients with chronic low back pain and healthy controls.
Interpreting these data is difficult, said Dr. Rozen. They may indicate that these psychiatric comorbidities are risk factors for new daily persistent headache. An equally plausible interpretation is that these patients have a different disorder (eg, Ehlers-Danlos syndrome) that encompasses these common traits. Finally, symptoms such as depression and catastrophization may be sequelae of, rather than risk factors for, new daily persistent headache.
Researchers have found imaging abnormalities to be rare in patients with new daily persistent headache. About two-thirds of patients in a 2002 study had normal MRI or CT results, and the rest had nonspecific findings unrelated to the headache. Dr. Rozen found that white matter lesions were uncommon in patients with this disorder, except for those with a history of migraine or cardiovascular or cerebrovascular risk factors. CSF likewise generally is normal in patients with new daily persistent headache.
Triggers Suggest Treatments
Goadsby proposed in 2011 that new daily persistent headache is a syndrome rather than a single disorder. “I’m completely in agreement,” said Dr. Rozen. “However, I do believe that individuals who have the same triggering event have the same pathogenesis.” Identifying the triggering event and understanding the temporal profile of the first headache can enable the choice of appropriate therapy, he added.
A patient whose persistent headache begins with a thunderclap onset likely has a prolonged cerebral artery vasospasm. Dr. Rozen treated a patient whose initial headache was a thunderclap; imaging ultimately revealed that she had a vasospasm. Her headache responded to nimodipine within days. Nimodipine generally provides relief within three to five days, said Dr. Rozen. If it worsens the headache, then the patient does not have vasospasm, he added.
Many patients with new daily persistent headache have a physical presentation that suggests Marfan syndrome. This observation led Dr. Rozen to hypothesize that cervical hypermobility is a risk factor for new daily persistent headache. Hypermobile patients may put significant stress on the C1, C2, and C3 joints, which are “where the trigeminal–cervical complex comes together,” said Dr. Rozen. A long plane ride or appointment with the dentist could trigger new daily persistent headache. Treatment with onabotulinumtoxinA often helps these patients. High cervical blocks also can bring relief, said Dr. Rozen.
He and his colleagues recently identified a new subset of patients with new daily persistent headache. They were older female patients with a mean age of 57 who suddenly developed the disorder. Most of them reported that the pain was worst before they got out of bed in the morning. Within seconds of assuming the Trendelenburg position, these patients had intensified pain and nausea, suggesting CSF hypertension. The patients all responded to acetazolamide or spironolactone, which lowered CSF pressure. “I think these individuals developed cerebral vein insufficiency because of estrogen withdrawal based on their age. Plus, the majority were overweight, which can also raise baseline CSF pressure.”
Examination Should Incorporate Imaging
All patients with new daily persistent headache should undergo imaging, including a brain MRI with and without gadolinium, plus an MR venogram, which can identify CSF leaks and a cerebral vein thrombosis, which are leading secondary causes of the disorder. Neurologists could examine patients’ viral titers in addition if the history suggests a post infectious trigger. A lumbar puncture and measurement of opening CSF pressure are appropriate for patients who have not responded to medication.
Evidence From the Literature
The literature possibly supports the efficacy of several treatments in new daily persistent headache, but includes no placebo-controlled trials for them. Dr. Rozen found doxycycline to be helpful for several patients with elevated CSF tumor necrosis factor alpha.
Marmura and colleagues found that mexiletine reduced the severity of pain in patients with refractory new daily persistent headache. The treatment did not reduce headache frequency, however, and side effects were common.
In a retrospective study, Prakash et al followed 63 patients with new daily persistent headache for five years. They found that patients who received IV methyl prednisolone and sodium valproate had a better response than patients who received other therapies. They called for prospective and controlled studies to confirm this observation.
In general, aggressive initial therapy is warranted, “especially if you meet an individual within one year of headache onset,” said Dr. Rozen. The likelihood of response to therapy appears to decline with the duration of the headache. “Infusion therapy or inpatient therapy with IV medications, even with standard migraine protocols, may help break the cycle,” Dr. Rozen concluded.
—Erik Greb
Suggested Reading
Goadsby PJ. New daily persistent headache: a syndrome, not a discrete disorder. Headache. 2011;51(4):650-653.
Marmura MJ, Passero FC Jr, Young WB. Mexiletine for refractory chronic daily headache: a report of nine cases. Headache. 2008;48(10):1506-1510.
Prakash S, Saini S, Rana KR, Mahato P. Refining clinical features and therapeutic options of new daily persistent headache: a retrospective study of 63 patients in India. J Headache Pain. 2012;13(6):477-485.
Rozen TD. A new subtype of chronic daily headache presenting in older women. J Womens Health (Larchmt). 2018;27(2):203-208.
Rozen TD. Triggering events and new daily persistent headache: age and gender differences and insights on pathogenesis-a clinic-based study. Headache. 2016;56(1):164-173.
Uniyal R, Paliwal VK, Tripathi A. Psychiatric comorbidity in new daily persistent headache: a cross-sectional study. Eur J Pain. 2017;21(6):1031-1038.
Aggressive initial therapy is appropriate because the disorder becomes increasingly refractory with time.
Aggressive initial therapy is appropriate because the disorder becomes increasingly refractory with time.
ASHEVILLE, NC—New daily persistent headache is rare and difficult to treat. Although neurologists may be tempted to try a series of treatments until the patient improves, therapeutic success is more likely if the neurologist can identify a triggering event, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. Elements of the patient’s history or clinical examination also can guide treatment, he added at the Eighth Annual Scientific Meeting of the Southern Headache Society.
Patients Remember the Onset
New daily persistent headache was first described in 1986, and few researchers have studied it. It is a persistent headache with a clearly remembered onset. “Most [patients] can name the date it began or at least the month,” said Dr. Rozen. The headache becomes unremitting within 24 hours and must be present for longer than three months, according to the current diagnostic criteria. Patients may have a remitting form, a relapsing-remitting form, or a refractory form of the headache. The age of onset “can be as early as in the mid to late teens or early 20s, especially in the female population,” said Dr. Rozen. Age of onset also depends on the triggering event.
The pain typically is bilateral and moderate to severe. Although many patients may present with a tension-type headache, more than 60% have migrainous symptoms such as nausea, photophobia, or phonophobia, said Dr. Rozen.
The disorder is more common among women than among men. Between 10% and 13% of patients who present to headache clinics have new daily persistent headache, said Dr. Rozen. “It is either becoming more prevalent in the office, or we are better at recognizing it.”
Comparing Effects on the Genders
For a study published in 2016, Dr. Rozen examined 97 patients (65 women) with new daily persistent headache. Approximately 53% of patients could not identify a triggering event for their headache, which makes treatment “much more difficult,” said Dr. Rozen. Although the mean age of onset was younger in women (32.4) than men (35.8), the age of onset was the same between genders when Dr. Rozen examined for individual triggers.
The frequency of individual triggering events also was the same between genders, and these results suggest that each trigger may be associated with a discrete pathogenesis. Triggers included infection or flulike illness (22%), stressful life event (9%), surgery (9%), and other (7%). All patients who had identified surgery as a trigger had been intubated, and Dr. Rozen hypothesized that their headaches were cervicogenic. The younger patients who had undergone surgery were hypermobile, and the older patients had neck arthritis as predisposing risk factors for neck irritation with intubation.
A Somatoform Disorder?
The stubbornly refractory nature of this disorder has aroused the suspicion that it may be somatoform. In 2017, Uniyal and colleagues found that somatization, generalized anxiety disorder, depression, and catastrophization were more common in patients with new daily persistent headache, compared with patients with chronic low back pain and healthy controls.
Interpreting these data is difficult, said Dr. Rozen. They may indicate that these psychiatric comorbidities are risk factors for new daily persistent headache. An equally plausible interpretation is that these patients have a different disorder (eg, Ehlers-Danlos syndrome) that encompasses these common traits. Finally, symptoms such as depression and catastrophization may be sequelae of, rather than risk factors for, new daily persistent headache.
Researchers have found imaging abnormalities to be rare in patients with new daily persistent headache. About two-thirds of patients in a 2002 study had normal MRI or CT results, and the rest had nonspecific findings unrelated to the headache. Dr. Rozen found that white matter lesions were uncommon in patients with this disorder, except for those with a history of migraine or cardiovascular or cerebrovascular risk factors. CSF likewise generally is normal in patients with new daily persistent headache.
Triggers Suggest Treatments
Goadsby proposed in 2011 that new daily persistent headache is a syndrome rather than a single disorder. “I’m completely in agreement,” said Dr. Rozen. “However, I do believe that individuals who have the same triggering event have the same pathogenesis.” Identifying the triggering event and understanding the temporal profile of the first headache can enable the choice of appropriate therapy, he added.
A patient whose persistent headache begins with a thunderclap onset likely has a prolonged cerebral artery vasospasm. Dr. Rozen treated a patient whose initial headache was a thunderclap; imaging ultimately revealed that she had a vasospasm. Her headache responded to nimodipine within days. Nimodipine generally provides relief within three to five days, said Dr. Rozen. If it worsens the headache, then the patient does not have vasospasm, he added.
Many patients with new daily persistent headache have a physical presentation that suggests Marfan syndrome. This observation led Dr. Rozen to hypothesize that cervical hypermobility is a risk factor for new daily persistent headache. Hypermobile patients may put significant stress on the C1, C2, and C3 joints, which are “where the trigeminal–cervical complex comes together,” said Dr. Rozen. A long plane ride or appointment with the dentist could trigger new daily persistent headache. Treatment with onabotulinumtoxinA often helps these patients. High cervical blocks also can bring relief, said Dr. Rozen.
He and his colleagues recently identified a new subset of patients with new daily persistent headache. They were older female patients with a mean age of 57 who suddenly developed the disorder. Most of them reported that the pain was worst before they got out of bed in the morning. Within seconds of assuming the Trendelenburg position, these patients had intensified pain and nausea, suggesting CSF hypertension. The patients all responded to acetazolamide or spironolactone, which lowered CSF pressure. “I think these individuals developed cerebral vein insufficiency because of estrogen withdrawal based on their age. Plus, the majority were overweight, which can also raise baseline CSF pressure.”
Examination Should Incorporate Imaging
All patients with new daily persistent headache should undergo imaging, including a brain MRI with and without gadolinium, plus an MR venogram, which can identify CSF leaks and a cerebral vein thrombosis, which are leading secondary causes of the disorder. Neurologists could examine patients’ viral titers in addition if the history suggests a post infectious trigger. A lumbar puncture and measurement of opening CSF pressure are appropriate for patients who have not responded to medication.
Evidence From the Literature
The literature possibly supports the efficacy of several treatments in new daily persistent headache, but includes no placebo-controlled trials for them. Dr. Rozen found doxycycline to be helpful for several patients with elevated CSF tumor necrosis factor alpha.
Marmura and colleagues found that mexiletine reduced the severity of pain in patients with refractory new daily persistent headache. The treatment did not reduce headache frequency, however, and side effects were common.
In a retrospective study, Prakash et al followed 63 patients with new daily persistent headache for five years. They found that patients who received IV methyl prednisolone and sodium valproate had a better response than patients who received other therapies. They called for prospective and controlled studies to confirm this observation.
In general, aggressive initial therapy is warranted, “especially if you meet an individual within one year of headache onset,” said Dr. Rozen. The likelihood of response to therapy appears to decline with the duration of the headache. “Infusion therapy or inpatient therapy with IV medications, even with standard migraine protocols, may help break the cycle,” Dr. Rozen concluded.
—Erik Greb
Suggested Reading
Goadsby PJ. New daily persistent headache: a syndrome, not a discrete disorder. Headache. 2011;51(4):650-653.
Marmura MJ, Passero FC Jr, Young WB. Mexiletine for refractory chronic daily headache: a report of nine cases. Headache. 2008;48(10):1506-1510.
Prakash S, Saini S, Rana KR, Mahato P. Refining clinical features and therapeutic options of new daily persistent headache: a retrospective study of 63 patients in India. J Headache Pain. 2012;13(6):477-485.
Rozen TD. A new subtype of chronic daily headache presenting in older women. J Womens Health (Larchmt). 2018;27(2):203-208.
Rozen TD. Triggering events and new daily persistent headache: age and gender differences and insights on pathogenesis-a clinic-based study. Headache. 2016;56(1):164-173.
Uniyal R, Paliwal VK, Tripathi A. Psychiatric comorbidity in new daily persistent headache: a cross-sectional study. Eur J Pain. 2017;21(6):1031-1038.
ASHEVILLE, NC—New daily persistent headache is rare and difficult to treat. Although neurologists may be tempted to try a series of treatments until the patient improves, therapeutic success is more likely if the neurologist can identify a triggering event, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. Elements of the patient’s history or clinical examination also can guide treatment, he added at the Eighth Annual Scientific Meeting of the Southern Headache Society.
Patients Remember the Onset
New daily persistent headache was first described in 1986, and few researchers have studied it. It is a persistent headache with a clearly remembered onset. “Most [patients] can name the date it began or at least the month,” said Dr. Rozen. The headache becomes unremitting within 24 hours and must be present for longer than three months, according to the current diagnostic criteria. Patients may have a remitting form, a relapsing-remitting form, or a refractory form of the headache. The age of onset “can be as early as in the mid to late teens or early 20s, especially in the female population,” said Dr. Rozen. Age of onset also depends on the triggering event.
The pain typically is bilateral and moderate to severe. Although many patients may present with a tension-type headache, more than 60% have migrainous symptoms such as nausea, photophobia, or phonophobia, said Dr. Rozen.
The disorder is more common among women than among men. Between 10% and 13% of patients who present to headache clinics have new daily persistent headache, said Dr. Rozen. “It is either becoming more prevalent in the office, or we are better at recognizing it.”
Comparing Effects on the Genders
For a study published in 2016, Dr. Rozen examined 97 patients (65 women) with new daily persistent headache. Approximately 53% of patients could not identify a triggering event for their headache, which makes treatment “much more difficult,” said Dr. Rozen. Although the mean age of onset was younger in women (32.4) than men (35.8), the age of onset was the same between genders when Dr. Rozen examined for individual triggers.
The frequency of individual triggering events also was the same between genders, and these results suggest that each trigger may be associated with a discrete pathogenesis. Triggers included infection or flulike illness (22%), stressful life event (9%), surgery (9%), and other (7%). All patients who had identified surgery as a trigger had been intubated, and Dr. Rozen hypothesized that their headaches were cervicogenic. The younger patients who had undergone surgery were hypermobile, and the older patients had neck arthritis as predisposing risk factors for neck irritation with intubation.
A Somatoform Disorder?
The stubbornly refractory nature of this disorder has aroused the suspicion that it may be somatoform. In 2017, Uniyal and colleagues found that somatization, generalized anxiety disorder, depression, and catastrophization were more common in patients with new daily persistent headache, compared with patients with chronic low back pain and healthy controls.
Interpreting these data is difficult, said Dr. Rozen. They may indicate that these psychiatric comorbidities are risk factors for new daily persistent headache. An equally plausible interpretation is that these patients have a different disorder (eg, Ehlers-Danlos syndrome) that encompasses these common traits. Finally, symptoms such as depression and catastrophization may be sequelae of, rather than risk factors for, new daily persistent headache.
Researchers have found imaging abnormalities to be rare in patients with new daily persistent headache. About two-thirds of patients in a 2002 study had normal MRI or CT results, and the rest had nonspecific findings unrelated to the headache. Dr. Rozen found that white matter lesions were uncommon in patients with this disorder, except for those with a history of migraine or cardiovascular or cerebrovascular risk factors. CSF likewise generally is normal in patients with new daily persistent headache.
Triggers Suggest Treatments
Goadsby proposed in 2011 that new daily persistent headache is a syndrome rather than a single disorder. “I’m completely in agreement,” said Dr. Rozen. “However, I do believe that individuals who have the same triggering event have the same pathogenesis.” Identifying the triggering event and understanding the temporal profile of the first headache can enable the choice of appropriate therapy, he added.
A patient whose persistent headache begins with a thunderclap onset likely has a prolonged cerebral artery vasospasm. Dr. Rozen treated a patient whose initial headache was a thunderclap; imaging ultimately revealed that she had a vasospasm. Her headache responded to nimodipine within days. Nimodipine generally provides relief within three to five days, said Dr. Rozen. If it worsens the headache, then the patient does not have vasospasm, he added.
Many patients with new daily persistent headache have a physical presentation that suggests Marfan syndrome. This observation led Dr. Rozen to hypothesize that cervical hypermobility is a risk factor for new daily persistent headache. Hypermobile patients may put significant stress on the C1, C2, and C3 joints, which are “where the trigeminal–cervical complex comes together,” said Dr. Rozen. A long plane ride or appointment with the dentist could trigger new daily persistent headache. Treatment with onabotulinumtoxinA often helps these patients. High cervical blocks also can bring relief, said Dr. Rozen.
He and his colleagues recently identified a new subset of patients with new daily persistent headache. They were older female patients with a mean age of 57 who suddenly developed the disorder. Most of them reported that the pain was worst before they got out of bed in the morning. Within seconds of assuming the Trendelenburg position, these patients had intensified pain and nausea, suggesting CSF hypertension. The patients all responded to acetazolamide or spironolactone, which lowered CSF pressure. “I think these individuals developed cerebral vein insufficiency because of estrogen withdrawal based on their age. Plus, the majority were overweight, which can also raise baseline CSF pressure.”
Examination Should Incorporate Imaging
All patients with new daily persistent headache should undergo imaging, including a brain MRI with and without gadolinium, plus an MR venogram, which can identify CSF leaks and a cerebral vein thrombosis, which are leading secondary causes of the disorder. Neurologists could examine patients’ viral titers in addition if the history suggests a post infectious trigger. A lumbar puncture and measurement of opening CSF pressure are appropriate for patients who have not responded to medication.
Evidence From the Literature
The literature possibly supports the efficacy of several treatments in new daily persistent headache, but includes no placebo-controlled trials for them. Dr. Rozen found doxycycline to be helpful for several patients with elevated CSF tumor necrosis factor alpha.
Marmura and colleagues found that mexiletine reduced the severity of pain in patients with refractory new daily persistent headache. The treatment did not reduce headache frequency, however, and side effects were common.
In a retrospective study, Prakash et al followed 63 patients with new daily persistent headache for five years. They found that patients who received IV methyl prednisolone and sodium valproate had a better response than patients who received other therapies. They called for prospective and controlled studies to confirm this observation.
In general, aggressive initial therapy is warranted, “especially if you meet an individual within one year of headache onset,” said Dr. Rozen. The likelihood of response to therapy appears to decline with the duration of the headache. “Infusion therapy or inpatient therapy with IV medications, even with standard migraine protocols, may help break the cycle,” Dr. Rozen concluded.
—Erik Greb
Suggested Reading
Goadsby PJ. New daily persistent headache: a syndrome, not a discrete disorder. Headache. 2011;51(4):650-653.
Marmura MJ, Passero FC Jr, Young WB. Mexiletine for refractory chronic daily headache: a report of nine cases. Headache. 2008;48(10):1506-1510.
Prakash S, Saini S, Rana KR, Mahato P. Refining clinical features and therapeutic options of new daily persistent headache: a retrospective study of 63 patients in India. J Headache Pain. 2012;13(6):477-485.
Rozen TD. A new subtype of chronic daily headache presenting in older women. J Womens Health (Larchmt). 2018;27(2):203-208.
Rozen TD. Triggering events and new daily persistent headache: age and gender differences and insights on pathogenesis-a clinic-based study. Headache. 2016;56(1):164-173.
Uniyal R, Paliwal VK, Tripathi A. Psychiatric comorbidity in new daily persistent headache: a cross-sectional study. Eur J Pain. 2017;21(6):1031-1038.
Complications cluster in inflammatory arthritis patients after total knee replacement
CHICAGO – Patients with an inflammatory arthritis had significantly higher rates of infections, transfusions, and readmissions following total knee replacement than did patients without inflammatory arthritis in a study of more than 137,000 Americans who underwent this surgery.
A sampling of U.S. patients who underwent total knee arthroplasty (TKA) during 2007-2016 showed that among the small percentage of these patients who had an inflammatory arthritis (IA), the rate of periprosthetic joint or wound infection while hospitalized or out to 30 days after surgery was a statistically significant 64% higher relative to patients without inflammatory arthritis, after adjustment for several demographic and clinical confounders, including recent glucocorticoid treatment, Susan M. Goodman, MD, said at the annual meeting of the American College of Rheumatology. The analysis also showed a statistically significant 46% higher relative rate of hospital readmission for any cause during the 90 days after surgery, and a significant 39% relative increase in blood transfusions during the 30 days after TKA in the IA patients.
“These results have important implications for evolving bundled payment models” for TKA, said Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York. “Hospitals should receive commensurate resources to maintain access to total TKA for patients with IA.”
For this analysis, Dr. Goodman and her associates classified IA as a patient with a recorded diagnosis of rheumatoid arthritis, spondyloarthritis, or systemic lupus erythematosus if the patient had also received treatment during the year before surgery with a disease-modifying antirheumatic drug, a biologic agent, or a drug that treats systemic lupus erythematosus.
Complications following TKA became a particular concern to hospitals starting in 2013 when the Centers for Medicare & Medicaid Services began a program that penalized hospitals for outcomes such as excessive readmissions following selected types of hospitalizations and also with recent steps to bundle TKA reimbursement with related 90-day outcomes.
“My concern is to ensure that patients with IA aren’t penalized and can maintain access” to TKA despite recent policy moves by the CMS. Faced with potential disincentives to treat patients with an IA, “hospitals might cherry pick patients,” Dr. Goodman said in an interview. The new findings “are a reason for administrators to argue for patients with IA to come out of the cost bundle.”
Dr. Goodman expressed hope that future policies will better reflect the higher levels of risk faced by patients with an IA undergoing TKA. CMS “is pretty responsive,” she said.
The study used data collected by Humana for about 25 million American health insurance beneficiaries during 2007-2016, which included 137,550 people who underwent a TKA. Of these, 3,067 (2%) met the study’s definition for IA, and 134,483 did not. Most of those who did not meet the definition likely had osteoarthritis, Dr. Goodman said. This low percentage of U.S. TKA patients with IA was consistent with numbers in prior reports.
The researchers calculated the relative risk of the IA patients, compared with all the others, for nine potential complications, including acute MI, pneumonia, sepsis, pulmonary embolism, and death. The complications with significantly higher rates among the IA patients after confounder adjustment were 30-day infections, 30-day transfusions, and 90-day readmissions.
Dr. Goodman had no relevant disclosures.
SOURCE: Richardson S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1932.
CHICAGO – Patients with an inflammatory arthritis had significantly higher rates of infections, transfusions, and readmissions following total knee replacement than did patients without inflammatory arthritis in a study of more than 137,000 Americans who underwent this surgery.
A sampling of U.S. patients who underwent total knee arthroplasty (TKA) during 2007-2016 showed that among the small percentage of these patients who had an inflammatory arthritis (IA), the rate of periprosthetic joint or wound infection while hospitalized or out to 30 days after surgery was a statistically significant 64% higher relative to patients without inflammatory arthritis, after adjustment for several demographic and clinical confounders, including recent glucocorticoid treatment, Susan M. Goodman, MD, said at the annual meeting of the American College of Rheumatology. The analysis also showed a statistically significant 46% higher relative rate of hospital readmission for any cause during the 90 days after surgery, and a significant 39% relative increase in blood transfusions during the 30 days after TKA in the IA patients.
“These results have important implications for evolving bundled payment models” for TKA, said Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York. “Hospitals should receive commensurate resources to maintain access to total TKA for patients with IA.”
For this analysis, Dr. Goodman and her associates classified IA as a patient with a recorded diagnosis of rheumatoid arthritis, spondyloarthritis, or systemic lupus erythematosus if the patient had also received treatment during the year before surgery with a disease-modifying antirheumatic drug, a biologic agent, or a drug that treats systemic lupus erythematosus.
Complications following TKA became a particular concern to hospitals starting in 2013 when the Centers for Medicare & Medicaid Services began a program that penalized hospitals for outcomes such as excessive readmissions following selected types of hospitalizations and also with recent steps to bundle TKA reimbursement with related 90-day outcomes.
“My concern is to ensure that patients with IA aren’t penalized and can maintain access” to TKA despite recent policy moves by the CMS. Faced with potential disincentives to treat patients with an IA, “hospitals might cherry pick patients,” Dr. Goodman said in an interview. The new findings “are a reason for administrators to argue for patients with IA to come out of the cost bundle.”
Dr. Goodman expressed hope that future policies will better reflect the higher levels of risk faced by patients with an IA undergoing TKA. CMS “is pretty responsive,” she said.
The study used data collected by Humana for about 25 million American health insurance beneficiaries during 2007-2016, which included 137,550 people who underwent a TKA. Of these, 3,067 (2%) met the study’s definition for IA, and 134,483 did not. Most of those who did not meet the definition likely had osteoarthritis, Dr. Goodman said. This low percentage of U.S. TKA patients with IA was consistent with numbers in prior reports.
The researchers calculated the relative risk of the IA patients, compared with all the others, for nine potential complications, including acute MI, pneumonia, sepsis, pulmonary embolism, and death. The complications with significantly higher rates among the IA patients after confounder adjustment were 30-day infections, 30-day transfusions, and 90-day readmissions.
Dr. Goodman had no relevant disclosures.
SOURCE: Richardson S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1932.
CHICAGO – Patients with an inflammatory arthritis had significantly higher rates of infections, transfusions, and readmissions following total knee replacement than did patients without inflammatory arthritis in a study of more than 137,000 Americans who underwent this surgery.
A sampling of U.S. patients who underwent total knee arthroplasty (TKA) during 2007-2016 showed that among the small percentage of these patients who had an inflammatory arthritis (IA), the rate of periprosthetic joint or wound infection while hospitalized or out to 30 days after surgery was a statistically significant 64% higher relative to patients without inflammatory arthritis, after adjustment for several demographic and clinical confounders, including recent glucocorticoid treatment, Susan M. Goodman, MD, said at the annual meeting of the American College of Rheumatology. The analysis also showed a statistically significant 46% higher relative rate of hospital readmission for any cause during the 90 days after surgery, and a significant 39% relative increase in blood transfusions during the 30 days after TKA in the IA patients.
“These results have important implications for evolving bundled payment models” for TKA, said Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York. “Hospitals should receive commensurate resources to maintain access to total TKA for patients with IA.”
For this analysis, Dr. Goodman and her associates classified IA as a patient with a recorded diagnosis of rheumatoid arthritis, spondyloarthritis, or systemic lupus erythematosus if the patient had also received treatment during the year before surgery with a disease-modifying antirheumatic drug, a biologic agent, or a drug that treats systemic lupus erythematosus.
Complications following TKA became a particular concern to hospitals starting in 2013 when the Centers for Medicare & Medicaid Services began a program that penalized hospitals for outcomes such as excessive readmissions following selected types of hospitalizations and also with recent steps to bundle TKA reimbursement with related 90-day outcomes.
“My concern is to ensure that patients with IA aren’t penalized and can maintain access” to TKA despite recent policy moves by the CMS. Faced with potential disincentives to treat patients with an IA, “hospitals might cherry pick patients,” Dr. Goodman said in an interview. The new findings “are a reason for administrators to argue for patients with IA to come out of the cost bundle.”
Dr. Goodman expressed hope that future policies will better reflect the higher levels of risk faced by patients with an IA undergoing TKA. CMS “is pretty responsive,” she said.
The study used data collected by Humana for about 25 million American health insurance beneficiaries during 2007-2016, which included 137,550 people who underwent a TKA. Of these, 3,067 (2%) met the study’s definition for IA, and 134,483 did not. Most of those who did not meet the definition likely had osteoarthritis, Dr. Goodman said. This low percentage of U.S. TKA patients with IA was consistent with numbers in prior reports.
The researchers calculated the relative risk of the IA patients, compared with all the others, for nine potential complications, including acute MI, pneumonia, sepsis, pulmonary embolism, and death. The complications with significantly higher rates among the IA patients after confounder adjustment were 30-day infections, 30-day transfusions, and 90-day readmissions.
Dr. Goodman had no relevant disclosures.
SOURCE: Richardson S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1932.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Complications were more common after total knee arthroplasty in patients with an inflammatory arthritis.
Major finding: Inflammatory arthritis patients had a 64% higher rate of infections after total knee arthroplasty, compared with patients without inflammatory arthritis.
Study details: Data analysis for 137,550 Americans who underwent total knee arthroplasty during 2007-2016.
Disclosures: Dr. Goodman had no relevant disclosures.
Source: Richardson S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1932.
Guideline authors inconsistently disclose conflicts
Financial conflicts are often underreported by authors of clinical practice guidelines (CPGs) in several specialties including oncology, rheumatology, and gastroenterology, according to a pair of research letters published in JAMA Internal Medicine. The Institute of Medicine recommends that guideline authors include no more than 50% individuals with financial conflicts.
In one research letter, Rishad Khan, BSc, of the University of Toronto in Ontario and his colleagues reviewed data on undeclared financial conflicts of interest among authors of guidelines related to high-revenue medications.
The researchers identified CPGs via the National Guideline Clearinghouse and selected 18 CPGs for 10 high-revenue medications published between 2013 and 2017. Financial conflicts of interest were based on the Centers for Medicare & Medicaid Services Open Payments.
Of the 160 authors involved in the various guidelines, 79 (49.4%) disclosed a payment in the CPG or supplemental materials, and 50 (31.3%) disclosed payments from companies marketing 1 of the 10 high-revenue medications in the related guidelines.
Another 41 authors (25.6%) received but did not disclose payments from companies marketing 1 of the 10 high-revenue medications in CPGs.
Overall, 91 authors (56.9%) were found to have financial conflicts of interest that involved 1 of the 10 high-revenue medications, and “the median value of undeclared payments from companies marketing 1 of the 10 high-revenue medications recommended in the CPGs was $522 (interquartile range, $0-$40,444) from two companies,” the researchers said.
The study findings were limited by several factors including “potential inaccuracies in CMS-OP reporting, which are rarely corrected, and lack of generalizability outside the United States” and by the limited time frame for data collection, which may have led to underestimation of conflicts for the guidelines, the researchers noted. In addition, “we did not have access to guideline voting records and thus did not know when conflicted panel members recommended against a medication or recused themselves from voting,” they said.
Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals.
In a second research letter, half of the authors of gastroenterology guidelines received payments from industry, wrote Tyler Combs, BS, of Oklahoma State University, Tulsa, and his colleagues. Previous studies have reviewed the financial conflicts of interest in specialties including oncology, dermatology, and otolaryngology, but financial conflicts of interest among authors of gastroenterology guidelines have not been examined, the researchers said.
Mr. Combs and his colleagues identified 15 CPGs published by the American College of Gastroenterology between 2014 and 2016. They identified 83 authors, with an average of 4 authors for each guideline. Overall, 53% of the authors received industry payments, according to based on data from the 2014 to 2016 Centers for Medicare and Medicaid Services Open Payments database (OPD).
However, OPD information was not always consistent with information published with the guidelines, the researchers noted. They found that 16 (19%) of the 83 authors both disclosed financial conflicts of interests in the CPGs and had received payments according to OPD or had disclosed no financial conflicts of interest and had received no payments according to OPD. In addition, 49 (34%) of 146 cumulative financial conflicts of interest disclosed in the CPGs and 148 relationships identified on OPD were both disclosed as financial conflicts of interest and evidenced by OPD payment records. In this review, the median total payment was $1,000, with an interquartile range from $0 to $39,938.
The study findings were limited by a relatively short 12-month time frame, the researchers noted. However, “our finding that FCOI [financial conflicts of interest] disclosure only corroborates with OPD payment records between 19% and 34% of the time also suggests that guidance from the ACG [American College of Gastroenterology] may be needed to improve FCOI disclosure efforts in future iterations of gastroenterology CPGs,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
None of the guidelines included in either study was fully compliant with National Academy of Medicine standards, which include written disclosure, appointing committee chairs or cochairs with no conflicts of interest, and keeping committee members with conflicts to a minority of the committee membership, wrote Colette DeJong, MD, and Robert Steinbrook, MD, in an accompanying editorial. In the study by Khan et al., “Notably, 14 of the 18 panels had chairs with industry payments, and 10 had a majority of members with payments,” they wrote.
However, the federal government has so far shown no interest in supporting a fully independent entity to develop clinical practice guidelines, as occurs in the United Kingdom via the National Institute for Health and Care Excellence. “Preparation of guidelines by an independent public body with assured funding and independence could be an effective approach, not only for eliminating issues related to financial conflicts of interest but also for assuring the use of rigorous methodologies and avoiding the wasteful duplication of efforts by multiple committees,” they wrote.
Financial conflicts in clinical practice guidelines persist in the United States in part because many professional societies have financial conflicts with industry, the editorialists wrote.
“Robust, objective, and unbiased clinical practice guidelines support improvements in patient care; the best interests of patients are the paramount consideration,” they emphasized (JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4974).
Dr. DeJong is affiliated with the University of California, San Francisco; Dr. Steinbrook is Editor at Large for JAMA Internal Medicine. They had no financial conflicts to disclose.
None of the guidelines included in either study was fully compliant with National Academy of Medicine standards, which include written disclosure, appointing committee chairs or cochairs with no conflicts of interest, and keeping committee members with conflicts to a minority of the committee membership, wrote Colette DeJong, MD, and Robert Steinbrook, MD, in an accompanying editorial. In the study by Khan et al., “Notably, 14 of the 18 panels had chairs with industry payments, and 10 had a majority of members with payments,” they wrote.
However, the federal government has so far shown no interest in supporting a fully independent entity to develop clinical practice guidelines, as occurs in the United Kingdom via the National Institute for Health and Care Excellence. “Preparation of guidelines by an independent public body with assured funding and independence could be an effective approach, not only for eliminating issues related to financial conflicts of interest but also for assuring the use of rigorous methodologies and avoiding the wasteful duplication of efforts by multiple committees,” they wrote.
Financial conflicts in clinical practice guidelines persist in the United States in part because many professional societies have financial conflicts with industry, the editorialists wrote.
“Robust, objective, and unbiased clinical practice guidelines support improvements in patient care; the best interests of patients are the paramount consideration,” they emphasized (JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4974).
Dr. DeJong is affiliated with the University of California, San Francisco; Dr. Steinbrook is Editor at Large for JAMA Internal Medicine. They had no financial conflicts to disclose.
None of the guidelines included in either study was fully compliant with National Academy of Medicine standards, which include written disclosure, appointing committee chairs or cochairs with no conflicts of interest, and keeping committee members with conflicts to a minority of the committee membership, wrote Colette DeJong, MD, and Robert Steinbrook, MD, in an accompanying editorial. In the study by Khan et al., “Notably, 14 of the 18 panels had chairs with industry payments, and 10 had a majority of members with payments,” they wrote.
However, the federal government has so far shown no interest in supporting a fully independent entity to develop clinical practice guidelines, as occurs in the United Kingdom via the National Institute for Health and Care Excellence. “Preparation of guidelines by an independent public body with assured funding and independence could be an effective approach, not only for eliminating issues related to financial conflicts of interest but also for assuring the use of rigorous methodologies and avoiding the wasteful duplication of efforts by multiple committees,” they wrote.
Financial conflicts in clinical practice guidelines persist in the United States in part because many professional societies have financial conflicts with industry, the editorialists wrote.
“Robust, objective, and unbiased clinical practice guidelines support improvements in patient care; the best interests of patients are the paramount consideration,” they emphasized (JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4974).
Dr. DeJong is affiliated with the University of California, San Francisco; Dr. Steinbrook is Editor at Large for JAMA Internal Medicine. They had no financial conflicts to disclose.
Financial conflicts are often underreported by authors of clinical practice guidelines (CPGs) in several specialties including oncology, rheumatology, and gastroenterology, according to a pair of research letters published in JAMA Internal Medicine. The Institute of Medicine recommends that guideline authors include no more than 50% individuals with financial conflicts.
In one research letter, Rishad Khan, BSc, of the University of Toronto in Ontario and his colleagues reviewed data on undeclared financial conflicts of interest among authors of guidelines related to high-revenue medications.
The researchers identified CPGs via the National Guideline Clearinghouse and selected 18 CPGs for 10 high-revenue medications published between 2013 and 2017. Financial conflicts of interest were based on the Centers for Medicare & Medicaid Services Open Payments.
Of the 160 authors involved in the various guidelines, 79 (49.4%) disclosed a payment in the CPG or supplemental materials, and 50 (31.3%) disclosed payments from companies marketing 1 of the 10 high-revenue medications in the related guidelines.
Another 41 authors (25.6%) received but did not disclose payments from companies marketing 1 of the 10 high-revenue medications in CPGs.
Overall, 91 authors (56.9%) were found to have financial conflicts of interest that involved 1 of the 10 high-revenue medications, and “the median value of undeclared payments from companies marketing 1 of the 10 high-revenue medications recommended in the CPGs was $522 (interquartile range, $0-$40,444) from two companies,” the researchers said.
The study findings were limited by several factors including “potential inaccuracies in CMS-OP reporting, which are rarely corrected, and lack of generalizability outside the United States” and by the limited time frame for data collection, which may have led to underestimation of conflicts for the guidelines, the researchers noted. In addition, “we did not have access to guideline voting records and thus did not know when conflicted panel members recommended against a medication or recused themselves from voting,” they said.
Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals.
In a second research letter, half of the authors of gastroenterology guidelines received payments from industry, wrote Tyler Combs, BS, of Oklahoma State University, Tulsa, and his colleagues. Previous studies have reviewed the financial conflicts of interest in specialties including oncology, dermatology, and otolaryngology, but financial conflicts of interest among authors of gastroenterology guidelines have not been examined, the researchers said.
Mr. Combs and his colleagues identified 15 CPGs published by the American College of Gastroenterology between 2014 and 2016. They identified 83 authors, with an average of 4 authors for each guideline. Overall, 53% of the authors received industry payments, according to based on data from the 2014 to 2016 Centers for Medicare and Medicaid Services Open Payments database (OPD).
However, OPD information was not always consistent with information published with the guidelines, the researchers noted. They found that 16 (19%) of the 83 authors both disclosed financial conflicts of interests in the CPGs and had received payments according to OPD or had disclosed no financial conflicts of interest and had received no payments according to OPD. In addition, 49 (34%) of 146 cumulative financial conflicts of interest disclosed in the CPGs and 148 relationships identified on OPD were both disclosed as financial conflicts of interest and evidenced by OPD payment records. In this review, the median total payment was $1,000, with an interquartile range from $0 to $39,938.
The study findings were limited by a relatively short 12-month time frame, the researchers noted. However, “our finding that FCOI [financial conflicts of interest] disclosure only corroborates with OPD payment records between 19% and 34% of the time also suggests that guidance from the ACG [American College of Gastroenterology] may be needed to improve FCOI disclosure efforts in future iterations of gastroenterology CPGs,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
Financial conflicts are often underreported by authors of clinical practice guidelines (CPGs) in several specialties including oncology, rheumatology, and gastroenterology, according to a pair of research letters published in JAMA Internal Medicine. The Institute of Medicine recommends that guideline authors include no more than 50% individuals with financial conflicts.
In one research letter, Rishad Khan, BSc, of the University of Toronto in Ontario and his colleagues reviewed data on undeclared financial conflicts of interest among authors of guidelines related to high-revenue medications.
The researchers identified CPGs via the National Guideline Clearinghouse and selected 18 CPGs for 10 high-revenue medications published between 2013 and 2017. Financial conflicts of interest were based on the Centers for Medicare & Medicaid Services Open Payments.
Of the 160 authors involved in the various guidelines, 79 (49.4%) disclosed a payment in the CPG or supplemental materials, and 50 (31.3%) disclosed payments from companies marketing 1 of the 10 high-revenue medications in the related guidelines.
Another 41 authors (25.6%) received but did not disclose payments from companies marketing 1 of the 10 high-revenue medications in CPGs.
Overall, 91 authors (56.9%) were found to have financial conflicts of interest that involved 1 of the 10 high-revenue medications, and “the median value of undeclared payments from companies marketing 1 of the 10 high-revenue medications recommended in the CPGs was $522 (interquartile range, $0-$40,444) from two companies,” the researchers said.
The study findings were limited by several factors including “potential inaccuracies in CMS-OP reporting, which are rarely corrected, and lack of generalizability outside the United States” and by the limited time frame for data collection, which may have led to underestimation of conflicts for the guidelines, the researchers noted. In addition, “we did not have access to guideline voting records and thus did not know when conflicted panel members recommended against a medication or recused themselves from voting,” they said.
Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals.
In a second research letter, half of the authors of gastroenterology guidelines received payments from industry, wrote Tyler Combs, BS, of Oklahoma State University, Tulsa, and his colleagues. Previous studies have reviewed the financial conflicts of interest in specialties including oncology, dermatology, and otolaryngology, but financial conflicts of interest among authors of gastroenterology guidelines have not been examined, the researchers said.
Mr. Combs and his colleagues identified 15 CPGs published by the American College of Gastroenterology between 2014 and 2016. They identified 83 authors, with an average of 4 authors for each guideline. Overall, 53% of the authors received industry payments, according to based on data from the 2014 to 2016 Centers for Medicare and Medicaid Services Open Payments database (OPD).
However, OPD information was not always consistent with information published with the guidelines, the researchers noted. They found that 16 (19%) of the 83 authors both disclosed financial conflicts of interests in the CPGs and had received payments according to OPD or had disclosed no financial conflicts of interest and had received no payments according to OPD. In addition, 49 (34%) of 146 cumulative financial conflicts of interest disclosed in the CPGs and 148 relationships identified on OPD were both disclosed as financial conflicts of interest and evidenced by OPD payment records. In this review, the median total payment was $1,000, with an interquartile range from $0 to $39,938.
The study findings were limited by a relatively short 12-month time frame, the researchers noted. However, “our finding that FCOI [financial conflicts of interest] disclosure only corroborates with OPD payment records between 19% and 34% of the time also suggests that guidance from the ACG [American College of Gastroenterology] may be needed to improve FCOI disclosure efforts in future iterations of gastroenterology CPGs,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Financial conflicts of interest in the development of clinical guidelines persist in the United States.
Major finding: Approximately half of the committee members of guidelines in both studies had financial relationships; many were undisclosed and involved substantial payments.
Study details: The data come from two research letters, including 15 gastroenterology guidelines and 18 guidelines from multiple specialties.
Disclosures: Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals. Mr. Combs had no financial conflicts to disclose.
Source: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
How Long Should Dual Antiplatelet Therapy Last After Stroke or TIA?
A 21-day period could maximize the therapy’s benefits and minimize the risk of major hemorrhage.
MONTREAL—The optimal length for dual antiplatelet therapy (DAPT) in patients with mild stroke or transient ischemic attack (TIA) is 21 days, according to a prespecified analysis of data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial that was presented at the 11th World Stroke Congress. This duration of combined treatment maximizes protection against major ischemic events while minimizing the extra risk of a major hemorrhage, the researchers said.
Clopidogrel Plus Aspirin or Aspirin Alone
The POINT trial randomized 4,881 patients with a recent mild stroke or TIA and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, DAPT decreased the incidence of a major ischemic event by 25% and more than doubled the rate of major hemorrhage.
The new prespecified analysis looked at outcomes on a weekly basis during 90 days of treatment. During the first 21 days, the rate of major hemorrhage events was 5.6% among those patients on aspirin alone and 3.6% among those on DAPT. Thus, DAPT was associated with a statistically significant 35% decrease in these adverse outcomes, said Jordan J. Elm, PhD, Associate Professor of Biostatistics at the Medical University of South Carolina in Charleston. During the subsequent 69 days of treatment, the incidence of major ischemic events was approximately 1% in both arms of the study, showing that after three weeks, the incremental benefit of DAPT disappeared, said Dr. Elm.
In contrast, the doubled rate of major hemorrhages (which mostly were reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment. This suggests that limiting DAPT to 21 days could prevent many of the excess hemorrhages, maximize benefit, and reduce risk, said Dr. Elm. The findings of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial confirmed the efficacy of 21 days of DAPT following a minor stroke or TIA.
Although the new finding from the POINT study resulted from a secondary analysis, it should be taken into account when writing treatment guidelines, said Dr. Elm. “This is an important analysis that is not just hypothesis-generating.”
Early Treatment
Another finding from the new analysis was that many major ischemic events, hence many of the events prevented by DAPT, occurred during the first two days following the index event. The POINT investigators were able to observe this finding because they enrolled patients and started treatment within 12 hours of the qualifying events.
“It is better to start treatment early,” said Dr. Elm. Major ischemic events continued to accumulate during Days 3 through 21, suggesting that patients could still benefit from DAPT if treatment did not start until 24 or 48 hours after the index event.
—Mitchel L. Zoler
Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379(3):215-225.
Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV. Recent advances in primary and secondary prevention of atherosclerotic stroke. J Stroke. 2018;20(2):145-166.
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11-19.
A 21-day period could maximize the therapy’s benefits and minimize the risk of major hemorrhage.
A 21-day period could maximize the therapy’s benefits and minimize the risk of major hemorrhage.
MONTREAL—The optimal length for dual antiplatelet therapy (DAPT) in patients with mild stroke or transient ischemic attack (TIA) is 21 days, according to a prespecified analysis of data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial that was presented at the 11th World Stroke Congress. This duration of combined treatment maximizes protection against major ischemic events while minimizing the extra risk of a major hemorrhage, the researchers said.
Clopidogrel Plus Aspirin or Aspirin Alone
The POINT trial randomized 4,881 patients with a recent mild stroke or TIA and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, DAPT decreased the incidence of a major ischemic event by 25% and more than doubled the rate of major hemorrhage.
The new prespecified analysis looked at outcomes on a weekly basis during 90 days of treatment. During the first 21 days, the rate of major hemorrhage events was 5.6% among those patients on aspirin alone and 3.6% among those on DAPT. Thus, DAPT was associated with a statistically significant 35% decrease in these adverse outcomes, said Jordan J. Elm, PhD, Associate Professor of Biostatistics at the Medical University of South Carolina in Charleston. During the subsequent 69 days of treatment, the incidence of major ischemic events was approximately 1% in both arms of the study, showing that after three weeks, the incremental benefit of DAPT disappeared, said Dr. Elm.
In contrast, the doubled rate of major hemorrhages (which mostly were reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment. This suggests that limiting DAPT to 21 days could prevent many of the excess hemorrhages, maximize benefit, and reduce risk, said Dr. Elm. The findings of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial confirmed the efficacy of 21 days of DAPT following a minor stroke or TIA.
Although the new finding from the POINT study resulted from a secondary analysis, it should be taken into account when writing treatment guidelines, said Dr. Elm. “This is an important analysis that is not just hypothesis-generating.”
Early Treatment
Another finding from the new analysis was that many major ischemic events, hence many of the events prevented by DAPT, occurred during the first two days following the index event. The POINT investigators were able to observe this finding because they enrolled patients and started treatment within 12 hours of the qualifying events.
“It is better to start treatment early,” said Dr. Elm. Major ischemic events continued to accumulate during Days 3 through 21, suggesting that patients could still benefit from DAPT if treatment did not start until 24 or 48 hours after the index event.
—Mitchel L. Zoler
Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379(3):215-225.
Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV. Recent advances in primary and secondary prevention of atherosclerotic stroke. J Stroke. 2018;20(2):145-166.
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11-19.
MONTREAL—The optimal length for dual antiplatelet therapy (DAPT) in patients with mild stroke or transient ischemic attack (TIA) is 21 days, according to a prespecified analysis of data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial that was presented at the 11th World Stroke Congress. This duration of combined treatment maximizes protection against major ischemic events while minimizing the extra risk of a major hemorrhage, the researchers said.
Clopidogrel Plus Aspirin or Aspirin Alone
The POINT trial randomized 4,881 patients with a recent mild stroke or TIA and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, DAPT decreased the incidence of a major ischemic event by 25% and more than doubled the rate of major hemorrhage.
The new prespecified analysis looked at outcomes on a weekly basis during 90 days of treatment. During the first 21 days, the rate of major hemorrhage events was 5.6% among those patients on aspirin alone and 3.6% among those on DAPT. Thus, DAPT was associated with a statistically significant 35% decrease in these adverse outcomes, said Jordan J. Elm, PhD, Associate Professor of Biostatistics at the Medical University of South Carolina in Charleston. During the subsequent 69 days of treatment, the incidence of major ischemic events was approximately 1% in both arms of the study, showing that after three weeks, the incremental benefit of DAPT disappeared, said Dr. Elm.
In contrast, the doubled rate of major hemorrhages (which mostly were reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment. This suggests that limiting DAPT to 21 days could prevent many of the excess hemorrhages, maximize benefit, and reduce risk, said Dr. Elm. The findings of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial confirmed the efficacy of 21 days of DAPT following a minor stroke or TIA.
Although the new finding from the POINT study resulted from a secondary analysis, it should be taken into account when writing treatment guidelines, said Dr. Elm. “This is an important analysis that is not just hypothesis-generating.”
Early Treatment
Another finding from the new analysis was that many major ischemic events, hence many of the events prevented by DAPT, occurred during the first two days following the index event. The POINT investigators were able to observe this finding because they enrolled patients and started treatment within 12 hours of the qualifying events.
“It is better to start treatment early,” said Dr. Elm. Major ischemic events continued to accumulate during Days 3 through 21, suggesting that patients could still benefit from DAPT if treatment did not start until 24 or 48 hours after the index event.
—Mitchel L. Zoler
Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379(3):215-225.
Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV. Recent advances in primary and secondary prevention of atherosclerotic stroke. J Stroke. 2018;20(2):145-166.
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11-19.
Quick Byte: Palliative care
Rapid adoption of a key program
In 2015, 75% of U.S. hospitals with more than 50 beds had palliative care programs – a sharp increase from the 25% that had palliative care in 2000.
“The rapid adoption of this high-value program, which is voluntary and runs counter to the dominant culture in U.S. hospitals, was catalyzed by tens of millions of dollars in philanthropic support for innovation, dissemination, and professionalization in the palliative care field,” according to research published in Health Affairs.
Reference
Cassel JB et al. Palliative care leadership centers are key to the diffusion of palliative care innovation. Health Aff. 2018 Feb. doi: 10.1377/hlthaff.2017.1122.
Rapid adoption of a key program
Rapid adoption of a key program
In 2015, 75% of U.S. hospitals with more than 50 beds had palliative care programs – a sharp increase from the 25% that had palliative care in 2000.
“The rapid adoption of this high-value program, which is voluntary and runs counter to the dominant culture in U.S. hospitals, was catalyzed by tens of millions of dollars in philanthropic support for innovation, dissemination, and professionalization in the palliative care field,” according to research published in Health Affairs.
Reference
Cassel JB et al. Palliative care leadership centers are key to the diffusion of palliative care innovation. Health Aff. 2018 Feb. doi: 10.1377/hlthaff.2017.1122.
In 2015, 75% of U.S. hospitals with more than 50 beds had palliative care programs – a sharp increase from the 25% that had palliative care in 2000.
“The rapid adoption of this high-value program, which is voluntary and runs counter to the dominant culture in U.S. hospitals, was catalyzed by tens of millions of dollars in philanthropic support for innovation, dissemination, and professionalization in the palliative care field,” according to research published in Health Affairs.
Reference
Cassel JB et al. Palliative care leadership centers are key to the diffusion of palliative care innovation. Health Aff. 2018 Feb. doi: 10.1377/hlthaff.2017.1122.
AAP president affirms academy’s support for transgender children
ORLANDO – Many Colleen A. Kraft, MD, president of the American Academy of Pediatrics, said in an interview.
The AAP’s policy on caring and supporting these patients is evidence-based, and includes recommendations on providing appropriate health care services for transgender individuals, as well as respect and understanding for families. In the interview, Dr. Kraft, discussed the role pediatricians have in providing a safe and supportive environment for transgender and gender-diverse individuals and their families.
“[These children] need to be listened to, they need to be respected for who they are, and they need access to the appropriate health services,” Dr. Kraft said.
The AAP’s policy statement on ensuring care and support for transgender children and adolescents is available here.
Dr. Kraft reported no relevant conflicts of interest.
ORLANDO – Many Colleen A. Kraft, MD, president of the American Academy of Pediatrics, said in an interview.
The AAP’s policy on caring and supporting these patients is evidence-based, and includes recommendations on providing appropriate health care services for transgender individuals, as well as respect and understanding for families. In the interview, Dr. Kraft, discussed the role pediatricians have in providing a safe and supportive environment for transgender and gender-diverse individuals and their families.
“[These children] need to be listened to, they need to be respected for who they are, and they need access to the appropriate health services,” Dr. Kraft said.
The AAP’s policy statement on ensuring care and support for transgender children and adolescents is available here.
Dr. Kraft reported no relevant conflicts of interest.
ORLANDO – Many Colleen A. Kraft, MD, president of the American Academy of Pediatrics, said in an interview.
The AAP’s policy on caring and supporting these patients is evidence-based, and includes recommendations on providing appropriate health care services for transgender individuals, as well as respect and understanding for families. In the interview, Dr. Kraft, discussed the role pediatricians have in providing a safe and supportive environment for transgender and gender-diverse individuals and their families.
“[These children] need to be listened to, they need to be respected for who they are, and they need access to the appropriate health services,” Dr. Kraft said.
The AAP’s policy statement on ensuring care and support for transgender children and adolescents is available here.
Dr. Kraft reported no relevant conflicts of interest.
REPORTING FROM AAP 2018
Heart drug spotlights troubling trends in drug marketing
At the end of September, Amarin Corp. teased some early findings for Vascepa, its preventive medicine for people at risk of heart disease. The claim was astounding: a 25% relative risk reduction for deaths related to heart attacks, strokes, and other conditions. Headlines proclaimed a potential game changer in treating cardiovascular disease. And company shares quickly soared, from $3 a share to about $20.
Vascepa is Amarin’s only product. The company hopes to turn its pill made of purified fish oil into a cash cow, allowing it to staff up both in the United States and abroad so it can sell doctors and millions of consumers on its medical benefits. Although the product has been on the market for more than 5 years, its first TV ad campaign rolled out this summer in anticipation of the study findings.
Except there is one problem. The particulars of the scientific study on which this claim was based remain a mystery.
Amarin’s preliminary announcement came via a news release on Sept. 24. The company plans to release detailed findings in November at the national American Heart Association conference. Then early next year, it plans to seek Food and Drug Administration approval to use the drug as a preventive for a range of heart conditions, beyond its current role targeting high triglyceride levels.
In the interim, a battle is brewing among physicians, cardiovascular experts, and pharma watchers who say Vascepa brings to the foreground troubling trends in the marketing and advertising of new drugs. Companies sometimes promote new products, but withhold the detailed findings until much later. The consequences for both consumers and the health system are vast.
“Until all the data is available for review by the public and medical community, it’s really premature to see some of the cheerleading that’s being done,” said Eric Strong, MD, a hospitalist and clinical assistant professor at Stanford (Calif.) University. “It’s harder to change people’s minds once you have these rosy pictures.”
John Thero, Amarin’s CEO, argued that the imminent release of the drug’s complete picture should alleviate those concerns.
In unveiling topline findings in a news release, he said, the company’s playbook doesn’t diverge from that of other pharmaceutical makers and provides a necessary level of disclosure for shareholders.
But it’s the specifics in the data – for instance, which patients benefited, by how much, their absolute risk reduction and which precise conditions saw improvement – that illustrate whether a product is cost effective, said medical and drug experts.
That’s especially true in the case of Vascepa, whose manufacturer is working hard to convince people the product is clinically superior to ordinary fish oil supplements. Fish oil, which can retail for a few dollars a bottle, has long been promoted as a preventive for heart disease. But the substance has never held up in clinical trials as a way to systematically lower disease risk, said experts.
That’s where Amarin’s product is superior, Mr. Thero said.
The manufacturer has tried to limit competition by seeking to block other fish oil products, arguing to the U.S. International Trade Commission that omega-3 supplements aren’t equivalents, and calling on the FDA to block a chemical component of fish oil, known as EPA or eicosapentaenoic acid, and marketed by a number of supplement companies, from being sold as a dietary supplement. Amarin hasn’t yet prevailed.
Preston Mason, PhD, a biologist and faculty member in the division of cardiology at Brigham and Women’s Hospital, Boston, who consults for Amarin and has advocated on its behalf, argued that ordinary fish oil supplements carry risks because they are not regulated or approved by the FDA, which does oversee prescription drugs like Vascepa.
How Vascepa performs against regular fish oil remains unknown. Amarin’s trial compared the drug against a placebo, not over-the-counter supplements.
Vascepa itself isn’t new. It was approved in 2012 as a remedy for extremely high triglyceride levels, which can put patients at risk for pancreatic problems. But reducing that fat hadn’t been conclusively tied to, say, lowering the risk of heart attacks, or other major cardiac problems.
That link, ostensibly, is what Amarin is trying now to assert. And there’s plenty of money to be made if it succeeds.
As of last December, Vascepa retailed for about $280 for a month-long supply, a list price increase of 43% over 5 years, though the company says its net sale price has stayed the same. (That difference would come if Amarin increased the size of rebates, or discounts it provides, commensurate with price hikes.)
Now, citing the drug’s potentially increased value, Amarin has declined to say whether it will change the price again – though Mr. Thero said he sees greater profit potential if the company increases sales volume rather than price.
This gets at the crux of this debate. If a company makes available the technical details of a product, but only after hyping the findings, and if the details undercut some of that buzz – is it too late?
Khurram Nasir, MD, a cardiologist at Yale University in New Haven, Conn., acknowledged that it’s unclear how effective Vascepa really is, but maintained those ambiguities will be cleared up soon enough.
“As the findings reveal themselves, there will be a lot of discussion around cost effectiveness, and whether this is worth the spend,” Dr. Nasir said.
Dr. Mason, the Amarin scientist, said FDA scrutiny also can alleviate concerns about overhype.
But others worry the perception of Vascepa’s effectiveness is now set.
“People are weighing in with really strong language, without enough information,” said Lisa Schwartz, MD, MS, who codirects the Center for Medicine and Media at Dartmouth Institute in Hanover, N.H., and studies effective scientific communication.
That has both clinical and financial consequences, she added. Doctors are more likely to prescribe a product that’s been heavily promoted, even if subsequent discussion indicates the drug isn’t as powerful as initially implied. And manufacturers can cash in, whether through increased company stock market value or by charging higher list prices.
For Vascepa, the central question is which specific heart conditions saw risk reduction, she and others said. In its news release, Amarin noted a “composite outcome” – that is, the 25% relative improvement encompassed all conditions for which the researchers tested.
“People are saying, Wow, it reduced heart attack, stroke and blah, blah, blah – when it may just reduce the least important one,” said Steven Woloshin, MD, MS, who also codirects the Center for Medicine and Media at Dartmouth.
Another issue: The Vascepa trial focused on a specific population — patients with high triglyceride levels plus elevated risk of cardiovascular disease or diabetes who were already taking a daily statin. That means any proof of benefit is limited to that group.
Dr. Woloshin and Dr. Schwartz both suggested that nuance could get lost in translation. “It is this much narrower, high-risk population,” Dr. Schwartz said.
Dr. Woloshin added, “The fear is [the message] would generalize to anyone with high triglycerides.”
This concern is amplified by a 2016 court settlement in which the FDA permitted Amarin to market Vascepa to audiences for whom it hasn’t been specifically approved – so long as the company doesn’t say anything untrue about the drug.
Mr. Thero said Amarin’s marketing of Vascepa has stayed, and will remain, consistent with what is factual and relevant.
“We are proceeding consistently with what the FDA has guided,” he said.
But, some experts said, the 2016 settlement could unlock the door to wider marketing of Vascepa’s off-label use, implying the pill benefits more people than it actually does.
“They’ll take pains to show how different this is from everything out there ... and its results in these populations,” said Ameet Sarpatwari, MD, JD, an epidemiologist and lawyer at Harvard Medical School, Boston, who studies the pharmaceutical industry. “What they can’t do is say it will be beneficial to these other populations. But they can hint at that.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
At the end of September, Amarin Corp. teased some early findings for Vascepa, its preventive medicine for people at risk of heart disease. The claim was astounding: a 25% relative risk reduction for deaths related to heart attacks, strokes, and other conditions. Headlines proclaimed a potential game changer in treating cardiovascular disease. And company shares quickly soared, from $3 a share to about $20.
Vascepa is Amarin’s only product. The company hopes to turn its pill made of purified fish oil into a cash cow, allowing it to staff up both in the United States and abroad so it can sell doctors and millions of consumers on its medical benefits. Although the product has been on the market for more than 5 years, its first TV ad campaign rolled out this summer in anticipation of the study findings.
Except there is one problem. The particulars of the scientific study on which this claim was based remain a mystery.
Amarin’s preliminary announcement came via a news release on Sept. 24. The company plans to release detailed findings in November at the national American Heart Association conference. Then early next year, it plans to seek Food and Drug Administration approval to use the drug as a preventive for a range of heart conditions, beyond its current role targeting high triglyceride levels.
In the interim, a battle is brewing among physicians, cardiovascular experts, and pharma watchers who say Vascepa brings to the foreground troubling trends in the marketing and advertising of new drugs. Companies sometimes promote new products, but withhold the detailed findings until much later. The consequences for both consumers and the health system are vast.
“Until all the data is available for review by the public and medical community, it’s really premature to see some of the cheerleading that’s being done,” said Eric Strong, MD, a hospitalist and clinical assistant professor at Stanford (Calif.) University. “It’s harder to change people’s minds once you have these rosy pictures.”
John Thero, Amarin’s CEO, argued that the imminent release of the drug’s complete picture should alleviate those concerns.
In unveiling topline findings in a news release, he said, the company’s playbook doesn’t diverge from that of other pharmaceutical makers and provides a necessary level of disclosure for shareholders.
But it’s the specifics in the data – for instance, which patients benefited, by how much, their absolute risk reduction and which precise conditions saw improvement – that illustrate whether a product is cost effective, said medical and drug experts.
That’s especially true in the case of Vascepa, whose manufacturer is working hard to convince people the product is clinically superior to ordinary fish oil supplements. Fish oil, which can retail for a few dollars a bottle, has long been promoted as a preventive for heart disease. But the substance has never held up in clinical trials as a way to systematically lower disease risk, said experts.
That’s where Amarin’s product is superior, Mr. Thero said.
The manufacturer has tried to limit competition by seeking to block other fish oil products, arguing to the U.S. International Trade Commission that omega-3 supplements aren’t equivalents, and calling on the FDA to block a chemical component of fish oil, known as EPA or eicosapentaenoic acid, and marketed by a number of supplement companies, from being sold as a dietary supplement. Amarin hasn’t yet prevailed.
Preston Mason, PhD, a biologist and faculty member in the division of cardiology at Brigham and Women’s Hospital, Boston, who consults for Amarin and has advocated on its behalf, argued that ordinary fish oil supplements carry risks because they are not regulated or approved by the FDA, which does oversee prescription drugs like Vascepa.
How Vascepa performs against regular fish oil remains unknown. Amarin’s trial compared the drug against a placebo, not over-the-counter supplements.
Vascepa itself isn’t new. It was approved in 2012 as a remedy for extremely high triglyceride levels, which can put patients at risk for pancreatic problems. But reducing that fat hadn’t been conclusively tied to, say, lowering the risk of heart attacks, or other major cardiac problems.
That link, ostensibly, is what Amarin is trying now to assert. And there’s plenty of money to be made if it succeeds.
As of last December, Vascepa retailed for about $280 for a month-long supply, a list price increase of 43% over 5 years, though the company says its net sale price has stayed the same. (That difference would come if Amarin increased the size of rebates, or discounts it provides, commensurate with price hikes.)
Now, citing the drug’s potentially increased value, Amarin has declined to say whether it will change the price again – though Mr. Thero said he sees greater profit potential if the company increases sales volume rather than price.
This gets at the crux of this debate. If a company makes available the technical details of a product, but only after hyping the findings, and if the details undercut some of that buzz – is it too late?
Khurram Nasir, MD, a cardiologist at Yale University in New Haven, Conn., acknowledged that it’s unclear how effective Vascepa really is, but maintained those ambiguities will be cleared up soon enough.
“As the findings reveal themselves, there will be a lot of discussion around cost effectiveness, and whether this is worth the spend,” Dr. Nasir said.
Dr. Mason, the Amarin scientist, said FDA scrutiny also can alleviate concerns about overhype.
But others worry the perception of Vascepa’s effectiveness is now set.
“People are weighing in with really strong language, without enough information,” said Lisa Schwartz, MD, MS, who codirects the Center for Medicine and Media at Dartmouth Institute in Hanover, N.H., and studies effective scientific communication.
That has both clinical and financial consequences, she added. Doctors are more likely to prescribe a product that’s been heavily promoted, even if subsequent discussion indicates the drug isn’t as powerful as initially implied. And manufacturers can cash in, whether through increased company stock market value or by charging higher list prices.
For Vascepa, the central question is which specific heart conditions saw risk reduction, she and others said. In its news release, Amarin noted a “composite outcome” – that is, the 25% relative improvement encompassed all conditions for which the researchers tested.
“People are saying, Wow, it reduced heart attack, stroke and blah, blah, blah – when it may just reduce the least important one,” said Steven Woloshin, MD, MS, who also codirects the Center for Medicine and Media at Dartmouth.
Another issue: The Vascepa trial focused on a specific population — patients with high triglyceride levels plus elevated risk of cardiovascular disease or diabetes who were already taking a daily statin. That means any proof of benefit is limited to that group.
Dr. Woloshin and Dr. Schwartz both suggested that nuance could get lost in translation. “It is this much narrower, high-risk population,” Dr. Schwartz said.
Dr. Woloshin added, “The fear is [the message] would generalize to anyone with high triglycerides.”
This concern is amplified by a 2016 court settlement in which the FDA permitted Amarin to market Vascepa to audiences for whom it hasn’t been specifically approved – so long as the company doesn’t say anything untrue about the drug.
Mr. Thero said Amarin’s marketing of Vascepa has stayed, and will remain, consistent with what is factual and relevant.
“We are proceeding consistently with what the FDA has guided,” he said.
But, some experts said, the 2016 settlement could unlock the door to wider marketing of Vascepa’s off-label use, implying the pill benefits more people than it actually does.
“They’ll take pains to show how different this is from everything out there ... and its results in these populations,” said Ameet Sarpatwari, MD, JD, an epidemiologist and lawyer at Harvard Medical School, Boston, who studies the pharmaceutical industry. “What they can’t do is say it will be beneficial to these other populations. But they can hint at that.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
At the end of September, Amarin Corp. teased some early findings for Vascepa, its preventive medicine for people at risk of heart disease. The claim was astounding: a 25% relative risk reduction for deaths related to heart attacks, strokes, and other conditions. Headlines proclaimed a potential game changer in treating cardiovascular disease. And company shares quickly soared, from $3 a share to about $20.
Vascepa is Amarin’s only product. The company hopes to turn its pill made of purified fish oil into a cash cow, allowing it to staff up both in the United States and abroad so it can sell doctors and millions of consumers on its medical benefits. Although the product has been on the market for more than 5 years, its first TV ad campaign rolled out this summer in anticipation of the study findings.
Except there is one problem. The particulars of the scientific study on which this claim was based remain a mystery.
Amarin’s preliminary announcement came via a news release on Sept. 24. The company plans to release detailed findings in November at the national American Heart Association conference. Then early next year, it plans to seek Food and Drug Administration approval to use the drug as a preventive for a range of heart conditions, beyond its current role targeting high triglyceride levels.
In the interim, a battle is brewing among physicians, cardiovascular experts, and pharma watchers who say Vascepa brings to the foreground troubling trends in the marketing and advertising of new drugs. Companies sometimes promote new products, but withhold the detailed findings until much later. The consequences for both consumers and the health system are vast.
“Until all the data is available for review by the public and medical community, it’s really premature to see some of the cheerleading that’s being done,” said Eric Strong, MD, a hospitalist and clinical assistant professor at Stanford (Calif.) University. “It’s harder to change people’s minds once you have these rosy pictures.”
John Thero, Amarin’s CEO, argued that the imminent release of the drug’s complete picture should alleviate those concerns.
In unveiling topline findings in a news release, he said, the company’s playbook doesn’t diverge from that of other pharmaceutical makers and provides a necessary level of disclosure for shareholders.
But it’s the specifics in the data – for instance, which patients benefited, by how much, their absolute risk reduction and which precise conditions saw improvement – that illustrate whether a product is cost effective, said medical and drug experts.
That’s especially true in the case of Vascepa, whose manufacturer is working hard to convince people the product is clinically superior to ordinary fish oil supplements. Fish oil, which can retail for a few dollars a bottle, has long been promoted as a preventive for heart disease. But the substance has never held up in clinical trials as a way to systematically lower disease risk, said experts.
That’s where Amarin’s product is superior, Mr. Thero said.
The manufacturer has tried to limit competition by seeking to block other fish oil products, arguing to the U.S. International Trade Commission that omega-3 supplements aren’t equivalents, and calling on the FDA to block a chemical component of fish oil, known as EPA or eicosapentaenoic acid, and marketed by a number of supplement companies, from being sold as a dietary supplement. Amarin hasn’t yet prevailed.
Preston Mason, PhD, a biologist and faculty member in the division of cardiology at Brigham and Women’s Hospital, Boston, who consults for Amarin and has advocated on its behalf, argued that ordinary fish oil supplements carry risks because they are not regulated or approved by the FDA, which does oversee prescription drugs like Vascepa.
How Vascepa performs against regular fish oil remains unknown. Amarin’s trial compared the drug against a placebo, not over-the-counter supplements.
Vascepa itself isn’t new. It was approved in 2012 as a remedy for extremely high triglyceride levels, which can put patients at risk for pancreatic problems. But reducing that fat hadn’t been conclusively tied to, say, lowering the risk of heart attacks, or other major cardiac problems.
That link, ostensibly, is what Amarin is trying now to assert. And there’s plenty of money to be made if it succeeds.
As of last December, Vascepa retailed for about $280 for a month-long supply, a list price increase of 43% over 5 years, though the company says its net sale price has stayed the same. (That difference would come if Amarin increased the size of rebates, or discounts it provides, commensurate with price hikes.)
Now, citing the drug’s potentially increased value, Amarin has declined to say whether it will change the price again – though Mr. Thero said he sees greater profit potential if the company increases sales volume rather than price.
This gets at the crux of this debate. If a company makes available the technical details of a product, but only after hyping the findings, and if the details undercut some of that buzz – is it too late?
Khurram Nasir, MD, a cardiologist at Yale University in New Haven, Conn., acknowledged that it’s unclear how effective Vascepa really is, but maintained those ambiguities will be cleared up soon enough.
“As the findings reveal themselves, there will be a lot of discussion around cost effectiveness, and whether this is worth the spend,” Dr. Nasir said.
Dr. Mason, the Amarin scientist, said FDA scrutiny also can alleviate concerns about overhype.
But others worry the perception of Vascepa’s effectiveness is now set.
“People are weighing in with really strong language, without enough information,” said Lisa Schwartz, MD, MS, who codirects the Center for Medicine and Media at Dartmouth Institute in Hanover, N.H., and studies effective scientific communication.
That has both clinical and financial consequences, she added. Doctors are more likely to prescribe a product that’s been heavily promoted, even if subsequent discussion indicates the drug isn’t as powerful as initially implied. And manufacturers can cash in, whether through increased company stock market value or by charging higher list prices.
For Vascepa, the central question is which specific heart conditions saw risk reduction, she and others said. In its news release, Amarin noted a “composite outcome” – that is, the 25% relative improvement encompassed all conditions for which the researchers tested.
“People are saying, Wow, it reduced heart attack, stroke and blah, blah, blah – when it may just reduce the least important one,” said Steven Woloshin, MD, MS, who also codirects the Center for Medicine and Media at Dartmouth.
Another issue: The Vascepa trial focused on a specific population — patients with high triglyceride levels plus elevated risk of cardiovascular disease or diabetes who were already taking a daily statin. That means any proof of benefit is limited to that group.
Dr. Woloshin and Dr. Schwartz both suggested that nuance could get lost in translation. “It is this much narrower, high-risk population,” Dr. Schwartz said.
Dr. Woloshin added, “The fear is [the message] would generalize to anyone with high triglycerides.”
This concern is amplified by a 2016 court settlement in which the FDA permitted Amarin to market Vascepa to audiences for whom it hasn’t been specifically approved – so long as the company doesn’t say anything untrue about the drug.
Mr. Thero said Amarin’s marketing of Vascepa has stayed, and will remain, consistent with what is factual and relevant.
“We are proceeding consistently with what the FDA has guided,” he said.
But, some experts said, the 2016 settlement could unlock the door to wider marketing of Vascepa’s off-label use, implying the pill benefits more people than it actually does.
“They’ll take pains to show how different this is from everything out there ... and its results in these populations,” said Ameet Sarpatwari, MD, JD, an epidemiologist and lawyer at Harvard Medical School, Boston, who studies the pharmaceutical industry. “What they can’t do is say it will be beneficial to these other populations. But they can hint at that.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Ultrasound excels for assessing shoulder dislocation
SAN DIEGO – Point-of-care ultrasound should be the go-to approach for the routine assessment of suspected shoulder dislocations in the ED, based on data from a prospective, multicenter study presented at the annual meeting of the American College of Emergency Physicians.
In the observational study, the average time needed to diagnose shoulder dislocation using ultrasound was 18 seconds, far faster than time from triage to x-ray, according to Michael Secko, MD, director of the emergency ultrasound division at Stony Brook University (NY).
The results from this study, called MUDDS (Musculoskeletal Ultrasound to Diagnose Dislocated Shoulders), support point-of-care ultrasound as a faster and more readily performed alternative to x-ray. Of the 46 adult patients enrolled so far in the ongoing study, ultrasound’s sensitivity has been 96% and its specificity 100% when validated by x-ray findings.
In the study, adults presenting to the ED are evaluated with point-of-care ultrasound from a posterior approach using either a curvilinear or linear transducer in the transverse plane. About half of the patients enrolled so far had injuries caused by falls, and many of the others had a shoulder complaint related to being pulled. Slightly more than one-third had a previous shoulder dislocation.
When evaluated with point-of-care ultrasound and x-ray, 23 of the 42 evaluable patients had a dislocation. The time from triage to ultrasound evaluation averaged 60 minutes, 40 minutes faster than the average of 100 minutes from triage to x-ray. Both tests were ordered at the same time.
Ultrasound performed less well for the diagnosis of a fracture, with a sensitivity of only 53%. Dr. Secko said the anterior approach would not be expected to provide a comprehensive assessment for fracture. He noted, for example, that there was no attempt in this study to evaluate patients for the presence of Bankart lesions. However, in those found to have a fracture on point-of-care ultrasound, the specificity of this imaging tool was 96%.
Ultimately, a major goal of this study was to determine whether a posterior point-of-care ultrasound could provide a quick answer to the question, “is it in or out?” Although patients are still being enrolled, Dr. Secko believed there is already good evidence that ultrasound is fast and effective for diagnosing dislocations.
Others have addressed this same question. Citing a meta-analysis published last year, Dr. Secko reported that all but one of four studies evaluating ultrasound for shoulder dislocations found a sensitivity and specificity of 100% (Gottlieb M et al. West J Emerg Med. 2017 Aug;18[5]:937-942).
Many centers have already switched to ultrasound for the evaluation of shoulder dislocations, according to Andrew S. Liteplo, MD, who moderated the ACEP session in which Dr. Secko presented his data. “If you are not already doing this for suspected shoulder dislocation, start right away because it is easy and awesome,” said Dr. Liteplo, who is chief of the division of ultrasound in emergency medicine at Massachusetts General Hospital, Boston. He also advised that ultrasound can also can be performed after reduction to confirm the efficacy of treatment.
Dr. Secko reported no financial relationships relevant to this study.
SAN DIEGO – Point-of-care ultrasound should be the go-to approach for the routine assessment of suspected shoulder dislocations in the ED, based on data from a prospective, multicenter study presented at the annual meeting of the American College of Emergency Physicians.
In the observational study, the average time needed to diagnose shoulder dislocation using ultrasound was 18 seconds, far faster than time from triage to x-ray, according to Michael Secko, MD, director of the emergency ultrasound division at Stony Brook University (NY).
The results from this study, called MUDDS (Musculoskeletal Ultrasound to Diagnose Dislocated Shoulders), support point-of-care ultrasound as a faster and more readily performed alternative to x-ray. Of the 46 adult patients enrolled so far in the ongoing study, ultrasound’s sensitivity has been 96% and its specificity 100% when validated by x-ray findings.
In the study, adults presenting to the ED are evaluated with point-of-care ultrasound from a posterior approach using either a curvilinear or linear transducer in the transverse plane. About half of the patients enrolled so far had injuries caused by falls, and many of the others had a shoulder complaint related to being pulled. Slightly more than one-third had a previous shoulder dislocation.
When evaluated with point-of-care ultrasound and x-ray, 23 of the 42 evaluable patients had a dislocation. The time from triage to ultrasound evaluation averaged 60 minutes, 40 minutes faster than the average of 100 minutes from triage to x-ray. Both tests were ordered at the same time.
Ultrasound performed less well for the diagnosis of a fracture, with a sensitivity of only 53%. Dr. Secko said the anterior approach would not be expected to provide a comprehensive assessment for fracture. He noted, for example, that there was no attempt in this study to evaluate patients for the presence of Bankart lesions. However, in those found to have a fracture on point-of-care ultrasound, the specificity of this imaging tool was 96%.
Ultimately, a major goal of this study was to determine whether a posterior point-of-care ultrasound could provide a quick answer to the question, “is it in or out?” Although patients are still being enrolled, Dr. Secko believed there is already good evidence that ultrasound is fast and effective for diagnosing dislocations.
Others have addressed this same question. Citing a meta-analysis published last year, Dr. Secko reported that all but one of four studies evaluating ultrasound for shoulder dislocations found a sensitivity and specificity of 100% (Gottlieb M et al. West J Emerg Med. 2017 Aug;18[5]:937-942).
Many centers have already switched to ultrasound for the evaluation of shoulder dislocations, according to Andrew S. Liteplo, MD, who moderated the ACEP session in which Dr. Secko presented his data. “If you are not already doing this for suspected shoulder dislocation, start right away because it is easy and awesome,” said Dr. Liteplo, who is chief of the division of ultrasound in emergency medicine at Massachusetts General Hospital, Boston. He also advised that ultrasound can also can be performed after reduction to confirm the efficacy of treatment.
Dr. Secko reported no financial relationships relevant to this study.
SAN DIEGO – Point-of-care ultrasound should be the go-to approach for the routine assessment of suspected shoulder dislocations in the ED, based on data from a prospective, multicenter study presented at the annual meeting of the American College of Emergency Physicians.
In the observational study, the average time needed to diagnose shoulder dislocation using ultrasound was 18 seconds, far faster than time from triage to x-ray, according to Michael Secko, MD, director of the emergency ultrasound division at Stony Brook University (NY).
The results from this study, called MUDDS (Musculoskeletal Ultrasound to Diagnose Dislocated Shoulders), support point-of-care ultrasound as a faster and more readily performed alternative to x-ray. Of the 46 adult patients enrolled so far in the ongoing study, ultrasound’s sensitivity has been 96% and its specificity 100% when validated by x-ray findings.
In the study, adults presenting to the ED are evaluated with point-of-care ultrasound from a posterior approach using either a curvilinear or linear transducer in the transverse plane. About half of the patients enrolled so far had injuries caused by falls, and many of the others had a shoulder complaint related to being pulled. Slightly more than one-third had a previous shoulder dislocation.
When evaluated with point-of-care ultrasound and x-ray, 23 of the 42 evaluable patients had a dislocation. The time from triage to ultrasound evaluation averaged 60 minutes, 40 minutes faster than the average of 100 minutes from triage to x-ray. Both tests were ordered at the same time.
Ultrasound performed less well for the diagnosis of a fracture, with a sensitivity of only 53%. Dr. Secko said the anterior approach would not be expected to provide a comprehensive assessment for fracture. He noted, for example, that there was no attempt in this study to evaluate patients for the presence of Bankart lesions. However, in those found to have a fracture on point-of-care ultrasound, the specificity of this imaging tool was 96%.
Ultimately, a major goal of this study was to determine whether a posterior point-of-care ultrasound could provide a quick answer to the question, “is it in or out?” Although patients are still being enrolled, Dr. Secko believed there is already good evidence that ultrasound is fast and effective for diagnosing dislocations.
Others have addressed this same question. Citing a meta-analysis published last year, Dr. Secko reported that all but one of four studies evaluating ultrasound for shoulder dislocations found a sensitivity and specificity of 100% (Gottlieb M et al. West J Emerg Med. 2017 Aug;18[5]:937-942).
Many centers have already switched to ultrasound for the evaluation of shoulder dislocations, according to Andrew S. Liteplo, MD, who moderated the ACEP session in which Dr. Secko presented his data. “If you are not already doing this for suspected shoulder dislocation, start right away because it is easy and awesome,” said Dr. Liteplo, who is chief of the division of ultrasound in emergency medicine at Massachusetts General Hospital, Boston. He also advised that ultrasound can also can be performed after reduction to confirm the efficacy of treatment.
Dr. Secko reported no financial relationships relevant to this study.
REPORTING FROM ACEP18
Key clinical point: Point-of-care ultrasound is accurate, simple, and fast, relative to x-ray, for the evaluation of shoulder dislocation.
Major finding: Based on results from 42 patients, time from triage to ultrasound, which had a sensitivity of 96% and specificity of 100%, was 60 minutes versus 100 minutes for x-ray.
Study details: An ongoing prospective, multicenter, observational study.
Disclosures: Dr. Secko reported no financial relationships relevant to this study.
FDA approves lorlatinib as second line for ALK-positive advanced NSCLC
The Food and Drug Administration has granted accelerated approval to lorlatinib for patients with anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval of the next-generation ALK inhibitor was based on an overall response rate of 48% – with 4% complete and 44% partial – in a subgroup of 215 patients with ALK-positive metastatic NSCLC enrolled in a nonrandomized, phase 2 trial, the FDA said in a press announcement. All patients had been previously treated with one or more ALK kinase inhibitors.
The median response duration was 12.5 months (95% confidence interval, 8.4-23.7) and the intracranial overall response rate in 89 patients with measurable lesions in the CNS was 60% (95% CI, 49-70) with 21% complete and 38% partial responses.
Common adverse reactions in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia, the FDA said.
The recommended dose of lorlatinib, to be marketed as Lorbrena by Pfizer, is 100 mg orally once daily.
The Food and Drug Administration has granted accelerated approval to lorlatinib for patients with anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval of the next-generation ALK inhibitor was based on an overall response rate of 48% – with 4% complete and 44% partial – in a subgroup of 215 patients with ALK-positive metastatic NSCLC enrolled in a nonrandomized, phase 2 trial, the FDA said in a press announcement. All patients had been previously treated with one or more ALK kinase inhibitors.
The median response duration was 12.5 months (95% confidence interval, 8.4-23.7) and the intracranial overall response rate in 89 patients with measurable lesions in the CNS was 60% (95% CI, 49-70) with 21% complete and 38% partial responses.
Common adverse reactions in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia, the FDA said.
The recommended dose of lorlatinib, to be marketed as Lorbrena by Pfizer, is 100 mg orally once daily.
The Food and Drug Administration has granted accelerated approval to lorlatinib for patients with anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval of the next-generation ALK inhibitor was based on an overall response rate of 48% – with 4% complete and 44% partial – in a subgroup of 215 patients with ALK-positive metastatic NSCLC enrolled in a nonrandomized, phase 2 trial, the FDA said in a press announcement. All patients had been previously treated with one or more ALK kinase inhibitors.
The median response duration was 12.5 months (95% confidence interval, 8.4-23.7) and the intracranial overall response rate in 89 patients with measurable lesions in the CNS was 60% (95% CI, 49-70) with 21% complete and 38% partial responses.
Common adverse reactions in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia, the FDA said.
The recommended dose of lorlatinib, to be marketed as Lorbrena by Pfizer, is 100 mg orally once daily.