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Depressive symptoms tied to higher stroke risk, worse outcomes
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Telehealth doctor indicted on health care fraud, opioid distribution charges
Sangita Patel, MD, 50, practiced at Advance Medical Home Physicians in Troy.
According to court documents, between July 2020 and June 2022 Patel was responsible for submitting Medicare claims for improper telehealth visits she didn’t conduct herself.
Dr. Patel, who accepted patients who paid in cash as well as those with Medicare and Medicaid coverage, billed approximately $3.4 million to Medicare between 2018 and 2022, according to court documents. An unusual number of these visits were billed using complex codes, an indication of health care fraud. The investigation also found that on many days, Dr. Patel billed for more than 24 hours of services. During this period, according to the document, 76% of Dr. Patel’s Medicare reimbursements were for telehealth.
Prosecutors say that Dr. Patel prescribed Schedule II controlled substances to more than 90% of the patients in these telehealth visits. She delegated her prescription authority to an unlicensed medical assistant. Through undercover visits and cell site search warrant data, the investigation found that Dr. Patel directed patients to contact, via cell phone, this assistant, who then entered electronic prescriptions into the electronic medical records system. Dr. Patel then signed the prescriptions and sent them to the pharmacies without ever interacting with the patients. Prosecutors also used text messages, obtained by search warrant, between Dr. Patel and her assistant and between the assistant and undercover informers to build their case.
Dr. Patel is also accused of referring patients to other providers, who in turn billed Medicare for claims associated with those patients. Advance Medical received $143,000 from these providers, potentially in violation of anti-kickback laws, according to bank records obtained by subpoena.
If convicted, Dr. Patel could be sentenced to up to 10 years in federal prison.
A version of this article first appeared on Medscape.com.
Sangita Patel, MD, 50, practiced at Advance Medical Home Physicians in Troy.
According to court documents, between July 2020 and June 2022 Patel was responsible for submitting Medicare claims for improper telehealth visits she didn’t conduct herself.
Dr. Patel, who accepted patients who paid in cash as well as those with Medicare and Medicaid coverage, billed approximately $3.4 million to Medicare between 2018 and 2022, according to court documents. An unusual number of these visits were billed using complex codes, an indication of health care fraud. The investigation also found that on many days, Dr. Patel billed for more than 24 hours of services. During this period, according to the document, 76% of Dr. Patel’s Medicare reimbursements were for telehealth.
Prosecutors say that Dr. Patel prescribed Schedule II controlled substances to more than 90% of the patients in these telehealth visits. She delegated her prescription authority to an unlicensed medical assistant. Through undercover visits and cell site search warrant data, the investigation found that Dr. Patel directed patients to contact, via cell phone, this assistant, who then entered electronic prescriptions into the electronic medical records system. Dr. Patel then signed the prescriptions and sent them to the pharmacies without ever interacting with the patients. Prosecutors also used text messages, obtained by search warrant, between Dr. Patel and her assistant and between the assistant and undercover informers to build their case.
Dr. Patel is also accused of referring patients to other providers, who in turn billed Medicare for claims associated with those patients. Advance Medical received $143,000 from these providers, potentially in violation of anti-kickback laws, according to bank records obtained by subpoena.
If convicted, Dr. Patel could be sentenced to up to 10 years in federal prison.
A version of this article first appeared on Medscape.com.
Sangita Patel, MD, 50, practiced at Advance Medical Home Physicians in Troy.
According to court documents, between July 2020 and June 2022 Patel was responsible for submitting Medicare claims for improper telehealth visits she didn’t conduct herself.
Dr. Patel, who accepted patients who paid in cash as well as those with Medicare and Medicaid coverage, billed approximately $3.4 million to Medicare between 2018 and 2022, according to court documents. An unusual number of these visits were billed using complex codes, an indication of health care fraud. The investigation also found that on many days, Dr. Patel billed for more than 24 hours of services. During this period, according to the document, 76% of Dr. Patel’s Medicare reimbursements were for telehealth.
Prosecutors say that Dr. Patel prescribed Schedule II controlled substances to more than 90% of the patients in these telehealth visits. She delegated her prescription authority to an unlicensed medical assistant. Through undercover visits and cell site search warrant data, the investigation found that Dr. Patel directed patients to contact, via cell phone, this assistant, who then entered electronic prescriptions into the electronic medical records system. Dr. Patel then signed the prescriptions and sent them to the pharmacies without ever interacting with the patients. Prosecutors also used text messages, obtained by search warrant, between Dr. Patel and her assistant and between the assistant and undercover informers to build their case.
Dr. Patel is also accused of referring patients to other providers, who in turn billed Medicare for claims associated with those patients. Advance Medical received $143,000 from these providers, potentially in violation of anti-kickback laws, according to bank records obtained by subpoena.
If convicted, Dr. Patel could be sentenced to up to 10 years in federal prison.
A version of this article first appeared on Medscape.com.
Migraine after concussion linked to worse outcomes
researchers have found.
“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”
Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.
Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.
The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.
Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.
Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.
The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.
Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.
The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.
Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.
“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”
Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.
“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.
The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
researchers have found.
“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”
Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.
Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.
The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.
Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.
Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.
The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.
Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.
The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.
Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.
“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”
Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.
“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.
The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
researchers have found.
“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”
Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.
Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.
The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.
Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.
Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.
The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.
Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.
The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.
Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.
“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”
Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.
“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.
The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
What’s it like to take Ozempic? A doctor’s own story
With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.
Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.
In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.
Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.
Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.
When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.
These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.
The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.
Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.
Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.
These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.
I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.
Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps.
When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.
With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.
The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).
Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.
Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.
Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.
For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.
As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.
Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.
Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.
In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.
Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.
Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.
When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.
These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.
The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.
Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.
Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.
These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.
I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.
Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps.
When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.
With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.
The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).
Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.
Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.
Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.
For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.
As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.
Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.
Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.
In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.
Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.
Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.
When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.
These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.
The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.
Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.
Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.
These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.
I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.
Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps.
When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.
With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.
The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).
Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.
Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.
Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.
For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.
As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.
Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
New documentary highlights human toll of high insulin cost
A new documentary premiering at the 2023 South by Southwest (SXSW) Festival illustrates the human consequences of insulin’s high cost in the United States. Its creators hope that it will help spur action toward overall prescription pricing reform.
Pay or Die: A Documentary is scheduled to premiere March 11. It will be shown twice more during the festival, which runs from March 10 to 19 in Austin, Texas. The documentary was co-created and directed by filmmaker and cinematographer Scott Alexander Ruderman, who has type 1 diabetes, and his partner, producer and journalist Rachael Dyer. One of the executive producers is Sarah Silverman, a comic, actor, producer, and health care reform advocate.
The 90-minute film follows three human stories: A mother and young daughter who both have type 1 diabetes and become homeless after spending their rent money on insulin, a young adult diagnosed during the COVID-19 pandemic, and a mother whose 26-year-old son died from diabetic ketoacidosis (DKA) after his insulin was rationed.
“As an Australian now living in the U.S. and seeing how the health care system works here, especially for people with type 1 diabetes like Scott, and how access to insulin is a life-or-death situation, has been very eye-opening for me. I’m also half Canadian, and both are countries where access to health care is a human right, not a business,” Ms. Dyer said in an interview.
In response to the March 1 announcement from Eli Lilly about its insulin price cut, the film’s team told this news organization: “While we commend Eli Lilly in taking this first step and hope that Novo Nordisk and Sanofi [the two other major insulin manufacturers] follow suit, it is important to remember that the key issue is not about these companies voluntarily slashing prices; it’s about changing laws so the insulin manufacturers do not have the ability to raise the prices again.
“This is the life-or-death issue that we focus on in our documentary Pay or Die. It’s also important to note that insulin is just one of the many expensive prescription drugs in the U.S., which is why we need to call for reform. Affordable medication needs to be a basic human right within reach for all Americans.”
Physician perspective: Good news on insulin, but broader issues
The film features four physicians. One, Mayo Clinic oncologist/hematologist S. Vincent Rajkumar, MD, has spoken and published widely on insulin prices specifically and U.S. drug costs more broadly.
The other three are Joslin Clinic endocrinologist Elizabeth Halprin, MD, Massachusetts General Hospital internist Leigh Simmons, MD, and New York University physician and essayist Danielle Ofri, MD, PhD.
In an interview after the Lilly announcement, Dr. Rajkumar said, “I think this is very, very good news for patients. ... The fact that they’re doing it means they’re listening to us and listening to patients, which is good. And I do hope that other insulin manufacturers do the same shortly.”
However, he added, “for prescription drug prices and particularly cancer drug prices, there’s more reform that’s needed, and that’s at the policy level. ... The goal of the film was to use insulin to highlight the prescription drug price problem in the U.S.”
‘Then life changed’
The filmmaker, Mr. Ruderman, was diagnosed at age 19, during his freshman year in college. He spent several days hospitalized with DKA, and “then life changed,” he said in an interview. He went into photography first and later filmmaking, always with the uneasy knowledge that he could lose access to insulin at any time.
The impetus for the film came after he and Ms. Dyer walked into a pharmacy while visiting Canada in 2018 and discovered how much cheaper insulin was compared to the United States – roughly $20 per vial, compared to $300 in the U.S.
“When Rachael [Dyer] and I came back to the U.S., we were actually quite shocked about how many people are struggling to afford their medication ... the uninsured, those aging off their parents’ health insurance. So that was really the kickoff to us going into the field for the last 4 years making this documentary.”
As a freelancer, Mr. Ruderman has been personally paying for expensive “premium” health insurance that covers the pump and glucose monitors he uses. He buys insulin overseas as often as possible.
“Fortunately, I haven’t been in a situation where I’ve had to ration my insulin, but the fear is instilled in me. What if there’s a month when I can’t afford it? What am I going to do?” (Note: The writer of this article is in the same situation, which could be alleviated by Lilly’s action.)
Timing is everything
To be sure, even before Lilly’s announcement, some progress had been made since work on the film began.
The issue of insulin pricing has received wide media attention. More than 20 states have passed copay caps on insulin, and a new law capping the cost of insulin for Medicare beneficiaries at $35/month went into effect in January 2023. President Biden mentioned insulin during his State of the Union address, and Georgia Senator Raphael Warnock made the issue a centerpiece of his campaign.
But there have also been losses, including the failure thus far to pass a nationwide copay cap.
These recent developments make this a good time for the film’s debut, producer Yael Melamede said in an interview. “There’s a lot happening in the space, but also a lot of incredible disappointments along the way, so we are really interested in getting this film out now.”
Ms. Melamede, who owns a film production company, said, “I’ve done a lot of films that have some issue advocacy side to them. I love this film because it’s grounded in the stories of real people. ... We feel this is a perfect catalyst to keep the energy going and for people to say this is super-important and not get distracted.”
While the film doesn’t advocate for specific policies, there is a “call to action” at the end that points viewers to resources on the website for writing to their members of Congress along with additional ways to become personally involved.
Ms. Dyer told this news organization, “This film is not only focusing on type 1 diabetes. That is obviously the crux of the issue, but it is a broader health care message for everyone wanting to make a change for health care in this country, the richest country in the world.”
At SXSW, Pay or Die will be competing with seven other films in the documentary feature competition, and it is eligible to win other awards.
Several other activities at the festival will address the topics of diabetes and U.S. health care costs, including a panel discussion titled Crushing: The Burden of Diabetes on Patients, featuring musician and actor Nick Jonas, who has type 1 diabetes, and a representative from the continuous glucose monitor manufacturer Dexcom.
Another panel, Young and Uninsured: Pay or Die, will include Dr. Rajkumar, Mr. Ruderman, Texas Representative James Talarico, who is advancing an insulin cap bill in that state, and Nicole Smith-Holt, the Minnesota mother of the young man who died because he couldn’t afford his insulin.
Mr. Ruderman, Ms. Dyer, Ms. Melamede, and Dr. Rajkumar have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new documentary premiering at the 2023 South by Southwest (SXSW) Festival illustrates the human consequences of insulin’s high cost in the United States. Its creators hope that it will help spur action toward overall prescription pricing reform.
Pay or Die: A Documentary is scheduled to premiere March 11. It will be shown twice more during the festival, which runs from March 10 to 19 in Austin, Texas. The documentary was co-created and directed by filmmaker and cinematographer Scott Alexander Ruderman, who has type 1 diabetes, and his partner, producer and journalist Rachael Dyer. One of the executive producers is Sarah Silverman, a comic, actor, producer, and health care reform advocate.
The 90-minute film follows three human stories: A mother and young daughter who both have type 1 diabetes and become homeless after spending their rent money on insulin, a young adult diagnosed during the COVID-19 pandemic, and a mother whose 26-year-old son died from diabetic ketoacidosis (DKA) after his insulin was rationed.
“As an Australian now living in the U.S. and seeing how the health care system works here, especially for people with type 1 diabetes like Scott, and how access to insulin is a life-or-death situation, has been very eye-opening for me. I’m also half Canadian, and both are countries where access to health care is a human right, not a business,” Ms. Dyer said in an interview.
In response to the March 1 announcement from Eli Lilly about its insulin price cut, the film’s team told this news organization: “While we commend Eli Lilly in taking this first step and hope that Novo Nordisk and Sanofi [the two other major insulin manufacturers] follow suit, it is important to remember that the key issue is not about these companies voluntarily slashing prices; it’s about changing laws so the insulin manufacturers do not have the ability to raise the prices again.
“This is the life-or-death issue that we focus on in our documentary Pay or Die. It’s also important to note that insulin is just one of the many expensive prescription drugs in the U.S., which is why we need to call for reform. Affordable medication needs to be a basic human right within reach for all Americans.”
Physician perspective: Good news on insulin, but broader issues
The film features four physicians. One, Mayo Clinic oncologist/hematologist S. Vincent Rajkumar, MD, has spoken and published widely on insulin prices specifically and U.S. drug costs more broadly.
The other three are Joslin Clinic endocrinologist Elizabeth Halprin, MD, Massachusetts General Hospital internist Leigh Simmons, MD, and New York University physician and essayist Danielle Ofri, MD, PhD.
In an interview after the Lilly announcement, Dr. Rajkumar said, “I think this is very, very good news for patients. ... The fact that they’re doing it means they’re listening to us and listening to patients, which is good. And I do hope that other insulin manufacturers do the same shortly.”
However, he added, “for prescription drug prices and particularly cancer drug prices, there’s more reform that’s needed, and that’s at the policy level. ... The goal of the film was to use insulin to highlight the prescription drug price problem in the U.S.”
‘Then life changed’
The filmmaker, Mr. Ruderman, was diagnosed at age 19, during his freshman year in college. He spent several days hospitalized with DKA, and “then life changed,” he said in an interview. He went into photography first and later filmmaking, always with the uneasy knowledge that he could lose access to insulin at any time.
The impetus for the film came after he and Ms. Dyer walked into a pharmacy while visiting Canada in 2018 and discovered how much cheaper insulin was compared to the United States – roughly $20 per vial, compared to $300 in the U.S.
“When Rachael [Dyer] and I came back to the U.S., we were actually quite shocked about how many people are struggling to afford their medication ... the uninsured, those aging off their parents’ health insurance. So that was really the kickoff to us going into the field for the last 4 years making this documentary.”
As a freelancer, Mr. Ruderman has been personally paying for expensive “premium” health insurance that covers the pump and glucose monitors he uses. He buys insulin overseas as often as possible.
“Fortunately, I haven’t been in a situation where I’ve had to ration my insulin, but the fear is instilled in me. What if there’s a month when I can’t afford it? What am I going to do?” (Note: The writer of this article is in the same situation, which could be alleviated by Lilly’s action.)
Timing is everything
To be sure, even before Lilly’s announcement, some progress had been made since work on the film began.
The issue of insulin pricing has received wide media attention. More than 20 states have passed copay caps on insulin, and a new law capping the cost of insulin for Medicare beneficiaries at $35/month went into effect in January 2023. President Biden mentioned insulin during his State of the Union address, and Georgia Senator Raphael Warnock made the issue a centerpiece of his campaign.
But there have also been losses, including the failure thus far to pass a nationwide copay cap.
These recent developments make this a good time for the film’s debut, producer Yael Melamede said in an interview. “There’s a lot happening in the space, but also a lot of incredible disappointments along the way, so we are really interested in getting this film out now.”
Ms. Melamede, who owns a film production company, said, “I’ve done a lot of films that have some issue advocacy side to them. I love this film because it’s grounded in the stories of real people. ... We feel this is a perfect catalyst to keep the energy going and for people to say this is super-important and not get distracted.”
While the film doesn’t advocate for specific policies, there is a “call to action” at the end that points viewers to resources on the website for writing to their members of Congress along with additional ways to become personally involved.
Ms. Dyer told this news organization, “This film is not only focusing on type 1 diabetes. That is obviously the crux of the issue, but it is a broader health care message for everyone wanting to make a change for health care in this country, the richest country in the world.”
At SXSW, Pay or Die will be competing with seven other films in the documentary feature competition, and it is eligible to win other awards.
Several other activities at the festival will address the topics of diabetes and U.S. health care costs, including a panel discussion titled Crushing: The Burden of Diabetes on Patients, featuring musician and actor Nick Jonas, who has type 1 diabetes, and a representative from the continuous glucose monitor manufacturer Dexcom.
Another panel, Young and Uninsured: Pay or Die, will include Dr. Rajkumar, Mr. Ruderman, Texas Representative James Talarico, who is advancing an insulin cap bill in that state, and Nicole Smith-Holt, the Minnesota mother of the young man who died because he couldn’t afford his insulin.
Mr. Ruderman, Ms. Dyer, Ms. Melamede, and Dr. Rajkumar have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new documentary premiering at the 2023 South by Southwest (SXSW) Festival illustrates the human consequences of insulin’s high cost in the United States. Its creators hope that it will help spur action toward overall prescription pricing reform.
Pay or Die: A Documentary is scheduled to premiere March 11. It will be shown twice more during the festival, which runs from March 10 to 19 in Austin, Texas. The documentary was co-created and directed by filmmaker and cinematographer Scott Alexander Ruderman, who has type 1 diabetes, and his partner, producer and journalist Rachael Dyer. One of the executive producers is Sarah Silverman, a comic, actor, producer, and health care reform advocate.
The 90-minute film follows three human stories: A mother and young daughter who both have type 1 diabetes and become homeless after spending their rent money on insulin, a young adult diagnosed during the COVID-19 pandemic, and a mother whose 26-year-old son died from diabetic ketoacidosis (DKA) after his insulin was rationed.
“As an Australian now living in the U.S. and seeing how the health care system works here, especially for people with type 1 diabetes like Scott, and how access to insulin is a life-or-death situation, has been very eye-opening for me. I’m also half Canadian, and both are countries where access to health care is a human right, not a business,” Ms. Dyer said in an interview.
In response to the March 1 announcement from Eli Lilly about its insulin price cut, the film’s team told this news organization: “While we commend Eli Lilly in taking this first step and hope that Novo Nordisk and Sanofi [the two other major insulin manufacturers] follow suit, it is important to remember that the key issue is not about these companies voluntarily slashing prices; it’s about changing laws so the insulin manufacturers do not have the ability to raise the prices again.
“This is the life-or-death issue that we focus on in our documentary Pay or Die. It’s also important to note that insulin is just one of the many expensive prescription drugs in the U.S., which is why we need to call for reform. Affordable medication needs to be a basic human right within reach for all Americans.”
Physician perspective: Good news on insulin, but broader issues
The film features four physicians. One, Mayo Clinic oncologist/hematologist S. Vincent Rajkumar, MD, has spoken and published widely on insulin prices specifically and U.S. drug costs more broadly.
The other three are Joslin Clinic endocrinologist Elizabeth Halprin, MD, Massachusetts General Hospital internist Leigh Simmons, MD, and New York University physician and essayist Danielle Ofri, MD, PhD.
In an interview after the Lilly announcement, Dr. Rajkumar said, “I think this is very, very good news for patients. ... The fact that they’re doing it means they’re listening to us and listening to patients, which is good. And I do hope that other insulin manufacturers do the same shortly.”
However, he added, “for prescription drug prices and particularly cancer drug prices, there’s more reform that’s needed, and that’s at the policy level. ... The goal of the film was to use insulin to highlight the prescription drug price problem in the U.S.”
‘Then life changed’
The filmmaker, Mr. Ruderman, was diagnosed at age 19, during his freshman year in college. He spent several days hospitalized with DKA, and “then life changed,” he said in an interview. He went into photography first and later filmmaking, always with the uneasy knowledge that he could lose access to insulin at any time.
The impetus for the film came after he and Ms. Dyer walked into a pharmacy while visiting Canada in 2018 and discovered how much cheaper insulin was compared to the United States – roughly $20 per vial, compared to $300 in the U.S.
“When Rachael [Dyer] and I came back to the U.S., we were actually quite shocked about how many people are struggling to afford their medication ... the uninsured, those aging off their parents’ health insurance. So that was really the kickoff to us going into the field for the last 4 years making this documentary.”
As a freelancer, Mr. Ruderman has been personally paying for expensive “premium” health insurance that covers the pump and glucose monitors he uses. He buys insulin overseas as often as possible.
“Fortunately, I haven’t been in a situation where I’ve had to ration my insulin, but the fear is instilled in me. What if there’s a month when I can’t afford it? What am I going to do?” (Note: The writer of this article is in the same situation, which could be alleviated by Lilly’s action.)
Timing is everything
To be sure, even before Lilly’s announcement, some progress had been made since work on the film began.
The issue of insulin pricing has received wide media attention. More than 20 states have passed copay caps on insulin, and a new law capping the cost of insulin for Medicare beneficiaries at $35/month went into effect in January 2023. President Biden mentioned insulin during his State of the Union address, and Georgia Senator Raphael Warnock made the issue a centerpiece of his campaign.
But there have also been losses, including the failure thus far to pass a nationwide copay cap.
These recent developments make this a good time for the film’s debut, producer Yael Melamede said in an interview. “There’s a lot happening in the space, but also a lot of incredible disappointments along the way, so we are really interested in getting this film out now.”
Ms. Melamede, who owns a film production company, said, “I’ve done a lot of films that have some issue advocacy side to them. I love this film because it’s grounded in the stories of real people. ... We feel this is a perfect catalyst to keep the energy going and for people to say this is super-important and not get distracted.”
While the film doesn’t advocate for specific policies, there is a “call to action” at the end that points viewers to resources on the website for writing to their members of Congress along with additional ways to become personally involved.
Ms. Dyer told this news organization, “This film is not only focusing on type 1 diabetes. That is obviously the crux of the issue, but it is a broader health care message for everyone wanting to make a change for health care in this country, the richest country in the world.”
At SXSW, Pay or Die will be competing with seven other films in the documentary feature competition, and it is eligible to win other awards.
Several other activities at the festival will address the topics of diabetes and U.S. health care costs, including a panel discussion titled Crushing: The Burden of Diabetes on Patients, featuring musician and actor Nick Jonas, who has type 1 diabetes, and a representative from the continuous glucose monitor manufacturer Dexcom.
Another panel, Young and Uninsured: Pay or Die, will include Dr. Rajkumar, Mr. Ruderman, Texas Representative James Talarico, who is advancing an insulin cap bill in that state, and Nicole Smith-Holt, the Minnesota mother of the young man who died because he couldn’t afford his insulin.
Mr. Ruderman, Ms. Dyer, Ms. Melamede, and Dr. Rajkumar have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
What do high BUN/Cr ratios mean?
He has been in good health with the only medical problem in his history being depression.
He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.
What is the most likely source of his bleeding?
A. Gastric ulcer
B. Meckel’s diverticulum
C. Arteriovenous malformation
D. Diverticulosis
E. Hemorrhoids
What makes the most sense
The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.
We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.
Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1
Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).
Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.
Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.
Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).
High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
Pearl
Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Emerg Med. 2006 May;24(3):280-5.
2. JAMA. 2012;307(10):1072-9.
3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.
4. Cardiorenal Med. 2020;10:415-28.
He has been in good health with the only medical problem in his history being depression.
He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.
What is the most likely source of his bleeding?
A. Gastric ulcer
B. Meckel’s diverticulum
C. Arteriovenous malformation
D. Diverticulosis
E. Hemorrhoids
What makes the most sense
The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.
We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.
Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1
Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).
Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.
Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.
Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).
High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
Pearl
Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Emerg Med. 2006 May;24(3):280-5.
2. JAMA. 2012;307(10):1072-9.
3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.
4. Cardiorenal Med. 2020;10:415-28.
He has been in good health with the only medical problem in his history being depression.
He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.
What is the most likely source of his bleeding?
A. Gastric ulcer
B. Meckel’s diverticulum
C. Arteriovenous malformation
D. Diverticulosis
E. Hemorrhoids
What makes the most sense
The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.
We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.
Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1
Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).
Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.
Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.
Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).
High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
Pearl
Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Emerg Med. 2006 May;24(3):280-5.
2. JAMA. 2012;307(10):1072-9.
3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.
4. Cardiorenal Med. 2020;10:415-28.
Commentary: Concerning PsA treatments and comorbidities, March 2023
With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.
In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.
Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.
With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.
In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.
Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.
With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.
In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.
Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.
PsA: Baseline disease activity predicts DAPSA response in patients treated with apremilast
Key clinical point: Nearly half of the patients with psoriatic arthritis (PsA) treated with apremilast achieved disease activity index for psoriatic arthritis (DAPSA) low disease activity/remission at 6 or 12 months, with lower baseline disease activity being the only factor associated with the achievement of low disease activity or remission.
Major finding: Overall, 42.7% and 54.9% of patients achieved DAPSA low disease activity or remission at 6 and 12 months, respectively. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio [OR] 0.84) and 12 months (OR 0.91; both P < .01).
Study details: Findings are from a retrospective study including 293 patients with PsA who were treated with apremilast.
Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.
Source: Becciolini A et al. Predictors of DAPSA response in psoriatic arthritis patients treated with apremilast in a retrospective observational multi-centric study. Biomedicines. 2023;11(2):433 (Feb 2). Doi: 10.3390/biomedicines11020433
Key clinical point: Nearly half of the patients with psoriatic arthritis (PsA) treated with apremilast achieved disease activity index for psoriatic arthritis (DAPSA) low disease activity/remission at 6 or 12 months, with lower baseline disease activity being the only factor associated with the achievement of low disease activity or remission.
Major finding: Overall, 42.7% and 54.9% of patients achieved DAPSA low disease activity or remission at 6 and 12 months, respectively. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio [OR] 0.84) and 12 months (OR 0.91; both P < .01).
Study details: Findings are from a retrospective study including 293 patients with PsA who were treated with apremilast.
Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.
Source: Becciolini A et al. Predictors of DAPSA response in psoriatic arthritis patients treated with apremilast in a retrospective observational multi-centric study. Biomedicines. 2023;11(2):433 (Feb 2). Doi: 10.3390/biomedicines11020433
Key clinical point: Nearly half of the patients with psoriatic arthritis (PsA) treated with apremilast achieved disease activity index for psoriatic arthritis (DAPSA) low disease activity/remission at 6 or 12 months, with lower baseline disease activity being the only factor associated with the achievement of low disease activity or remission.
Major finding: Overall, 42.7% and 54.9% of patients achieved DAPSA low disease activity or remission at 6 and 12 months, respectively. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio [OR] 0.84) and 12 months (OR 0.91; both P < .01).
Study details: Findings are from a retrospective study including 293 patients with PsA who were treated with apremilast.
Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.
Source: Becciolini A et al. Predictors of DAPSA response in psoriatic arthritis patients treated with apremilast in a retrospective observational multi-centric study. Biomedicines. 2023;11(2):433 (Feb 2). Doi: 10.3390/biomedicines11020433
Long-term safety and tolerability of upadacitinib in PsA
Key clinical point: Upadacitinib demonstrated an acceptable long-term safety profile and was generally well tolerated with no new safety signals in patients with psoriatic arthritis (PsA).
Major finding: Overall, patients with PsA receiving 15 mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and deaths (0.8/100 PY).
Study details: This integrated safety analysis of 12 phase 3 trials included 6991 patients with PsA (n = 907), rheumatoid arthritis (n = 3,209), ankylosing spondylitis (n = 182), and atopic dermatitis (n = 2693) who received upadacitinib (15 or 30 mg once daily); 1008 patients with RA (n = 579) and PsA (n = 429) who received 40 mg adalimumab every other week; and 314 patients with RA who received methotrexate.
Disclosures: This study was funded by AbbVie. Five authors declared being full-time employees of AbbVie or Mount Sinai or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.
Source: Burmester GR et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735;15(Feb 8). Doi: 10.1136/rmdopen-2022-002735
Key clinical point: Upadacitinib demonstrated an acceptable long-term safety profile and was generally well tolerated with no new safety signals in patients with psoriatic arthritis (PsA).
Major finding: Overall, patients with PsA receiving 15 mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and deaths (0.8/100 PY).
Study details: This integrated safety analysis of 12 phase 3 trials included 6991 patients with PsA (n = 907), rheumatoid arthritis (n = 3,209), ankylosing spondylitis (n = 182), and atopic dermatitis (n = 2693) who received upadacitinib (15 or 30 mg once daily); 1008 patients with RA (n = 579) and PsA (n = 429) who received 40 mg adalimumab every other week; and 314 patients with RA who received methotrexate.
Disclosures: This study was funded by AbbVie. Five authors declared being full-time employees of AbbVie or Mount Sinai or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.
Source: Burmester GR et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735;15(Feb 8). Doi: 10.1136/rmdopen-2022-002735
Key clinical point: Upadacitinib demonstrated an acceptable long-term safety profile and was generally well tolerated with no new safety signals in patients with psoriatic arthritis (PsA).
Major finding: Overall, patients with PsA receiving 15 mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and deaths (0.8/100 PY).
Study details: This integrated safety analysis of 12 phase 3 trials included 6991 patients with PsA (n = 907), rheumatoid arthritis (n = 3,209), ankylosing spondylitis (n = 182), and atopic dermatitis (n = 2693) who received upadacitinib (15 or 30 mg once daily); 1008 patients with RA (n = 579) and PsA (n = 429) who received 40 mg adalimumab every other week; and 314 patients with RA who received methotrexate.
Disclosures: This study was funded by AbbVie. Five authors declared being full-time employees of AbbVie or Mount Sinai or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.
Source: Burmester GR et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735;15(Feb 8). Doi: 10.1136/rmdopen-2022-002735
Baseline cardiovascular risk may influence MACE and malignancy incidences in tofacitinib-treated PsA patients
Key clinical point: Preventive monitoring for cardiovascular risk is suggested in tofacitinib-treated patients with psoriatic arthritis (PsA) as higher atherosclerotic cardiovascular disease (ASCVD) risk appears to be associated with a higher incidence of major cardiovascular events (MACE) and malignancies.
Major finding: The risk for MACE appeared to be higher among patients with PsA and high vs low 10-year ASCVD risk (incidence rate [IR] 1.37 [95% CI 0.03-7.63] vs 0.08 [95% CI 0.0-0.42]), with the incidence of malignancies being the highest in patients with PsA and an intermediate 10-year ASCVD risk (IR 2.56, 95% CI 1.11-5.05).
Study details: Findings are from a post hoc analysis of 10 clinical trials including patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib.
Disclosures: This study was sponsored by Pfizer. Some authors declared receiving speaker fees or grant or research support or serving as consultants for various sources, including Pfizer. Some authors declared being employees and shareholders of Pfizer or Syneos Health, a paid contractor to Pfizer.
Source: Kristensen LE et al. Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib. Ther Adv Musculoskelet Dis. 2023 (Feb 7). Doi: 10.1177/1759720X221149965
Key clinical point: Preventive monitoring for cardiovascular risk is suggested in tofacitinib-treated patients with psoriatic arthritis (PsA) as higher atherosclerotic cardiovascular disease (ASCVD) risk appears to be associated with a higher incidence of major cardiovascular events (MACE) and malignancies.
Major finding: The risk for MACE appeared to be higher among patients with PsA and high vs low 10-year ASCVD risk (incidence rate [IR] 1.37 [95% CI 0.03-7.63] vs 0.08 [95% CI 0.0-0.42]), with the incidence of malignancies being the highest in patients with PsA and an intermediate 10-year ASCVD risk (IR 2.56, 95% CI 1.11-5.05).
Study details: Findings are from a post hoc analysis of 10 clinical trials including patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib.
Disclosures: This study was sponsored by Pfizer. Some authors declared receiving speaker fees or grant or research support or serving as consultants for various sources, including Pfizer. Some authors declared being employees and shareholders of Pfizer or Syneos Health, a paid contractor to Pfizer.
Source: Kristensen LE et al. Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib. Ther Adv Musculoskelet Dis. 2023 (Feb 7). Doi: 10.1177/1759720X221149965
Key clinical point: Preventive monitoring for cardiovascular risk is suggested in tofacitinib-treated patients with psoriatic arthritis (PsA) as higher atherosclerotic cardiovascular disease (ASCVD) risk appears to be associated with a higher incidence of major cardiovascular events (MACE) and malignancies.
Major finding: The risk for MACE appeared to be higher among patients with PsA and high vs low 10-year ASCVD risk (incidence rate [IR] 1.37 [95% CI 0.03-7.63] vs 0.08 [95% CI 0.0-0.42]), with the incidence of malignancies being the highest in patients with PsA and an intermediate 10-year ASCVD risk (IR 2.56, 95% CI 1.11-5.05).
Study details: Findings are from a post hoc analysis of 10 clinical trials including patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib.
Disclosures: This study was sponsored by Pfizer. Some authors declared receiving speaker fees or grant or research support or serving as consultants for various sources, including Pfizer. Some authors declared being employees and shareholders of Pfizer or Syneos Health, a paid contractor to Pfizer.
Source: Kristensen LE et al. Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib. Ther Adv Musculoskelet Dis. 2023 (Feb 7). Doi: 10.1177/1759720X221149965