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When to suspect a severe skin reaction to an AED
NEW ORLEANS – Most skin eruptions in patients taking antiepileptic drugs (AEDs) are relatively benign. With close supervision, some patients with epilepsy may continue treatment despite having a benign drug rash, according to a lecture at the annual meeting of the American Epilepsy Society.
“When do you know that you’re not dealing with that kind of eruption?” said Jeanne M. Young, MD, assistant professor of dermatology at the University of Virginia in Charlottesville.
Signs and symptoms that raise concerns about severe cutaneous reactions include swelling of the face; lesions that are fluid-filled, dusky, or painful; mucus membrane involvement; and signs of systemic involvement.
Associations with anticonvulsants
Diffuse swelling of the face is a hallmark symptom of DRESS. Fluid-filled lesions such as pustules, vesicles, and bullae indicate a condition other than a benign drug eruption. Signs of systemic involvement may include fever, marked eosinophilia, transaminitis, and evidence of lymphocyte activation. “In general, I want to see systemic involvement that can’t be explained by the patient’s other systemic diseases,” Dr. Young said.
A 2018 study found that AEDs are associated with SJS and TEN, and the labels for lamotrigine and carbamazepine include black box warnings about the risk of severe cutaneous adverse events. Carbamazepine’s warning, which was added in 2007, notes that SJS and TEN are significantly more common in patients of Asian ancestry with the human leukocyte antigen allele HLA-B*1502 and that physicians should screen at-risk patients before starting treatment.
Benign drug rashes
Morbilliform drug eruptions, sometimes called benign exanthems, are “by far the most common drug rash that we see” and typically are “the rashes that people refer to as drug rashes,” Dr. Young said. The mechanisms appear to be primarily immune complex mediated and cell mediated. “When the drug is stopped, these rashes tend to go away quite predictably in 2-3 weeks.”
For any class of drug, about 1% of people taking that medication may have this type of reaction, Dr. Young said. “We expect to see erythematous papules and plaques that oftentimes become confluent on the skin.” These reactions generally occur 7-10 days after the first exposure to the medication, and most patients do not have other symptoms, although the rash may itch. In addition, patients may have erythroderma with desquamation. “I think it’s important to point out the difference between desquamation, which is loss of the stratum corneum, and epidermal sloughing, which is what you see in something like [SJS] or TEN, where you’re actually losing the entire epidermis,” Dr. Young said. Recovering from desquamation is “sort of like recovering from a sun burn, and it’s not particularly dangerous.” Management of morbilliform drug eruptions is largely symptomatic.
Treat through, taper, or rechallenge
In the case a benign drug rash, “if you feel like you … need to keep a patient on a drug, you do have that option with close supervision,” Dr. Young said. “Communicate that with the dermatologist. Say, ‘I have really struggled getting this patient stabilized. Can we keep them on this drug?’ ”
The dermatologist may not fully realize the implications of stopping an effective AED in a patient with seizures that have been difficult to control. If the drug rash is benign, treating through may be an option. Patients often resolve the rash while continuing the medication, which may be because of desensitization, Dr. Young said. If a patient’s symptoms are too great to continue the drug, neurologists have the option of slowly tapering the drug and reinitiating with a new drug, Dr. Young said. Neurologists also may choose to rechallenge.
If a patient is on several medications, making it difficult to elucidate a causative agent, after stopping those drugs and allowing the rash to resolve, “there is little danger in restarting a medication,” she said.
Benign rash or DRESS?
“When I see a morbilliform eruption, usually what’s on my mind is, ‘Is this just a drug rash or is this DRESS?’ ” Dr. Young said. DRESS often starts with a morbilliform eruption that is indistinguishable from a benign drug eruption.
“Timing is a major difference,” she said. “If a patient develops a morbilliform drug eruption much later than I would expect, then my suspicion [for DRESS] goes up.” Patients with DRESS often have fever and systemic symptoms. Proposed DRESS diagnostic criteria can be useful, but clinical judgment still plays a key role. If a patient does not satisfy diagnostic criteria but has some signs and is taking a drug that is associated with DRESS, “it is going to make me more suspicious and maybe make me recommend stopping that drug sooner,” she said. Anticonvulsants such as carbamazepine, lamotrigine, and phenobarbital are among the drugs most commonly associated with DRESS.
Toxic erythemas
Patients may present with toxic erythemas, such as fixed drug reactions, erythema multiforme, SJS, and TEN. These drug reactions appear similar on biopsy but have different courses.
A patient with a fixed drug reaction often has a single lesion, and the lesion will occur in the same location every time the patient is exposed to the drug. Patients may develop additional lesions with subsequent exposures. These lesions typically are large, erythematous, well-demarcated plaques with central duskiness. “They can be bullous in the center, and they typically will heal with pigmentation, which is unique to this particular drug reaction,” said Dr. Young. “When it gets more concerning and most important to differentiate is when you get generalized bullous fixed drug eruption.” Generalized bullous fixed drug eruptions mimic and are difficult to clinically distinguish from TEN, which has a much has a much poorer prognosis.
Patients with a fixed drug eruption are not as ill as patients with TEN and tend not to slough their skin to the extent seen with TEN. Interferon gamma, perforin, and Fas ligand have been implicated as mechanisms involved in fixed drug reactions. Unlike in TEN, regulatory T cells are abundant, which may explain why TEN and fixed drug reactions progress differently even though they appear to share pathologic mechanisms, Dr. Young said.
Erythema multiforme generally presents with classic target lesions and little mucosal involvement. Infections, most commonly herpes simplex virus (HSV) 1 and 2, may trigger erythema multiforme. Dr. Young recommends evaluating patients for HSV and checking serologies, even if patients have never had a herpes outbreak. “If you have no evidence for infection, you do have to consider discontinuing a medication,” she said.
Stevens–Johnson syndrome and TEN
SJS and TEN are “the rarest of the severe cutaneous adverse drug reactions” and have “the highest morbidity and mortality,” Dr. Young said. They appear to exist on a continuum where SJS may represent early TEN.
“This is a situation where you expect to see blistering of the skin [and] always mucosal involvement. You need to stop the drug immediately when you suspect this drug reaction,” Dr. Young said.
One reason to distinguish SJS or early TEN from later TEN is that high-dose steroids may play a role in the treatment of SJS or early TEN. “Once you get past about 10% total body surface area, there is good evidence that steroids actually increase morbidity and mortality,” she said.
If the eruption has occurred before, that factor suggests that a diagnosis of erythema multiforme or fixed drug reaction may be more likely than TEN.
An apparent lack of regulatory T cells in TEN could explain why patients with HIV infection are at much higher risk of developing SJS and TEN. Understanding the role that regulatory T cells play in severe drug eruptions may lead to new therapeutic options in the future, Dr. Young said.
Dr. Young had no disclosures.
NEW ORLEANS – Most skin eruptions in patients taking antiepileptic drugs (AEDs) are relatively benign. With close supervision, some patients with epilepsy may continue treatment despite having a benign drug rash, according to a lecture at the annual meeting of the American Epilepsy Society.
“When do you know that you’re not dealing with that kind of eruption?” said Jeanne M. Young, MD, assistant professor of dermatology at the University of Virginia in Charlottesville.
Signs and symptoms that raise concerns about severe cutaneous reactions include swelling of the face; lesions that are fluid-filled, dusky, or painful; mucus membrane involvement; and signs of systemic involvement.
Associations with anticonvulsants
Diffuse swelling of the face is a hallmark symptom of DRESS. Fluid-filled lesions such as pustules, vesicles, and bullae indicate a condition other than a benign drug eruption. Signs of systemic involvement may include fever, marked eosinophilia, transaminitis, and evidence of lymphocyte activation. “In general, I want to see systemic involvement that can’t be explained by the patient’s other systemic diseases,” Dr. Young said.
A 2018 study found that AEDs are associated with SJS and TEN, and the labels for lamotrigine and carbamazepine include black box warnings about the risk of severe cutaneous adverse events. Carbamazepine’s warning, which was added in 2007, notes that SJS and TEN are significantly more common in patients of Asian ancestry with the human leukocyte antigen allele HLA-B*1502 and that physicians should screen at-risk patients before starting treatment.
Benign drug rashes
Morbilliform drug eruptions, sometimes called benign exanthems, are “by far the most common drug rash that we see” and typically are “the rashes that people refer to as drug rashes,” Dr. Young said. The mechanisms appear to be primarily immune complex mediated and cell mediated. “When the drug is stopped, these rashes tend to go away quite predictably in 2-3 weeks.”
For any class of drug, about 1% of people taking that medication may have this type of reaction, Dr. Young said. “We expect to see erythematous papules and plaques that oftentimes become confluent on the skin.” These reactions generally occur 7-10 days after the first exposure to the medication, and most patients do not have other symptoms, although the rash may itch. In addition, patients may have erythroderma with desquamation. “I think it’s important to point out the difference between desquamation, which is loss of the stratum corneum, and epidermal sloughing, which is what you see in something like [SJS] or TEN, where you’re actually losing the entire epidermis,” Dr. Young said. Recovering from desquamation is “sort of like recovering from a sun burn, and it’s not particularly dangerous.” Management of morbilliform drug eruptions is largely symptomatic.
Treat through, taper, or rechallenge
In the case a benign drug rash, “if you feel like you … need to keep a patient on a drug, you do have that option with close supervision,” Dr. Young said. “Communicate that with the dermatologist. Say, ‘I have really struggled getting this patient stabilized. Can we keep them on this drug?’ ”
The dermatologist may not fully realize the implications of stopping an effective AED in a patient with seizures that have been difficult to control. If the drug rash is benign, treating through may be an option. Patients often resolve the rash while continuing the medication, which may be because of desensitization, Dr. Young said. If a patient’s symptoms are too great to continue the drug, neurologists have the option of slowly tapering the drug and reinitiating with a new drug, Dr. Young said. Neurologists also may choose to rechallenge.
If a patient is on several medications, making it difficult to elucidate a causative agent, after stopping those drugs and allowing the rash to resolve, “there is little danger in restarting a medication,” she said.
Benign rash or DRESS?
“When I see a morbilliform eruption, usually what’s on my mind is, ‘Is this just a drug rash or is this DRESS?’ ” Dr. Young said. DRESS often starts with a morbilliform eruption that is indistinguishable from a benign drug eruption.
“Timing is a major difference,” she said. “If a patient develops a morbilliform drug eruption much later than I would expect, then my suspicion [for DRESS] goes up.” Patients with DRESS often have fever and systemic symptoms. Proposed DRESS diagnostic criteria can be useful, but clinical judgment still plays a key role. If a patient does not satisfy diagnostic criteria but has some signs and is taking a drug that is associated with DRESS, “it is going to make me more suspicious and maybe make me recommend stopping that drug sooner,” she said. Anticonvulsants such as carbamazepine, lamotrigine, and phenobarbital are among the drugs most commonly associated with DRESS.
Toxic erythemas
Patients may present with toxic erythemas, such as fixed drug reactions, erythema multiforme, SJS, and TEN. These drug reactions appear similar on biopsy but have different courses.
A patient with a fixed drug reaction often has a single lesion, and the lesion will occur in the same location every time the patient is exposed to the drug. Patients may develop additional lesions with subsequent exposures. These lesions typically are large, erythematous, well-demarcated plaques with central duskiness. “They can be bullous in the center, and they typically will heal with pigmentation, which is unique to this particular drug reaction,” said Dr. Young. “When it gets more concerning and most important to differentiate is when you get generalized bullous fixed drug eruption.” Generalized bullous fixed drug eruptions mimic and are difficult to clinically distinguish from TEN, which has a much has a much poorer prognosis.
Patients with a fixed drug eruption are not as ill as patients with TEN and tend not to slough their skin to the extent seen with TEN. Interferon gamma, perforin, and Fas ligand have been implicated as mechanisms involved in fixed drug reactions. Unlike in TEN, regulatory T cells are abundant, which may explain why TEN and fixed drug reactions progress differently even though they appear to share pathologic mechanisms, Dr. Young said.
Erythema multiforme generally presents with classic target lesions and little mucosal involvement. Infections, most commonly herpes simplex virus (HSV) 1 and 2, may trigger erythema multiforme. Dr. Young recommends evaluating patients for HSV and checking serologies, even if patients have never had a herpes outbreak. “If you have no evidence for infection, you do have to consider discontinuing a medication,” she said.
Stevens–Johnson syndrome and TEN
SJS and TEN are “the rarest of the severe cutaneous adverse drug reactions” and have “the highest morbidity and mortality,” Dr. Young said. They appear to exist on a continuum where SJS may represent early TEN.
“This is a situation where you expect to see blistering of the skin [and] always mucosal involvement. You need to stop the drug immediately when you suspect this drug reaction,” Dr. Young said.
One reason to distinguish SJS or early TEN from later TEN is that high-dose steroids may play a role in the treatment of SJS or early TEN. “Once you get past about 10% total body surface area, there is good evidence that steroids actually increase morbidity and mortality,” she said.
If the eruption has occurred before, that factor suggests that a diagnosis of erythema multiforme or fixed drug reaction may be more likely than TEN.
An apparent lack of regulatory T cells in TEN could explain why patients with HIV infection are at much higher risk of developing SJS and TEN. Understanding the role that regulatory T cells play in severe drug eruptions may lead to new therapeutic options in the future, Dr. Young said.
Dr. Young had no disclosures.
NEW ORLEANS – Most skin eruptions in patients taking antiepileptic drugs (AEDs) are relatively benign. With close supervision, some patients with epilepsy may continue treatment despite having a benign drug rash, according to a lecture at the annual meeting of the American Epilepsy Society.
“When do you know that you’re not dealing with that kind of eruption?” said Jeanne M. Young, MD, assistant professor of dermatology at the University of Virginia in Charlottesville.
Signs and symptoms that raise concerns about severe cutaneous reactions include swelling of the face; lesions that are fluid-filled, dusky, or painful; mucus membrane involvement; and signs of systemic involvement.
Associations with anticonvulsants
Diffuse swelling of the face is a hallmark symptom of DRESS. Fluid-filled lesions such as pustules, vesicles, and bullae indicate a condition other than a benign drug eruption. Signs of systemic involvement may include fever, marked eosinophilia, transaminitis, and evidence of lymphocyte activation. “In general, I want to see systemic involvement that can’t be explained by the patient’s other systemic diseases,” Dr. Young said.
A 2018 study found that AEDs are associated with SJS and TEN, and the labels for lamotrigine and carbamazepine include black box warnings about the risk of severe cutaneous adverse events. Carbamazepine’s warning, which was added in 2007, notes that SJS and TEN are significantly more common in patients of Asian ancestry with the human leukocyte antigen allele HLA-B*1502 and that physicians should screen at-risk patients before starting treatment.
Benign drug rashes
Morbilliform drug eruptions, sometimes called benign exanthems, are “by far the most common drug rash that we see” and typically are “the rashes that people refer to as drug rashes,” Dr. Young said. The mechanisms appear to be primarily immune complex mediated and cell mediated. “When the drug is stopped, these rashes tend to go away quite predictably in 2-3 weeks.”
For any class of drug, about 1% of people taking that medication may have this type of reaction, Dr. Young said. “We expect to see erythematous papules and plaques that oftentimes become confluent on the skin.” These reactions generally occur 7-10 days after the first exposure to the medication, and most patients do not have other symptoms, although the rash may itch. In addition, patients may have erythroderma with desquamation. “I think it’s important to point out the difference between desquamation, which is loss of the stratum corneum, and epidermal sloughing, which is what you see in something like [SJS] or TEN, where you’re actually losing the entire epidermis,” Dr. Young said. Recovering from desquamation is “sort of like recovering from a sun burn, and it’s not particularly dangerous.” Management of morbilliform drug eruptions is largely symptomatic.
Treat through, taper, or rechallenge
In the case a benign drug rash, “if you feel like you … need to keep a patient on a drug, you do have that option with close supervision,” Dr. Young said. “Communicate that with the dermatologist. Say, ‘I have really struggled getting this patient stabilized. Can we keep them on this drug?’ ”
The dermatologist may not fully realize the implications of stopping an effective AED in a patient with seizures that have been difficult to control. If the drug rash is benign, treating through may be an option. Patients often resolve the rash while continuing the medication, which may be because of desensitization, Dr. Young said. If a patient’s symptoms are too great to continue the drug, neurologists have the option of slowly tapering the drug and reinitiating with a new drug, Dr. Young said. Neurologists also may choose to rechallenge.
If a patient is on several medications, making it difficult to elucidate a causative agent, after stopping those drugs and allowing the rash to resolve, “there is little danger in restarting a medication,” she said.
Benign rash or DRESS?
“When I see a morbilliform eruption, usually what’s on my mind is, ‘Is this just a drug rash or is this DRESS?’ ” Dr. Young said. DRESS often starts with a morbilliform eruption that is indistinguishable from a benign drug eruption.
“Timing is a major difference,” she said. “If a patient develops a morbilliform drug eruption much later than I would expect, then my suspicion [for DRESS] goes up.” Patients with DRESS often have fever and systemic symptoms. Proposed DRESS diagnostic criteria can be useful, but clinical judgment still plays a key role. If a patient does not satisfy diagnostic criteria but has some signs and is taking a drug that is associated with DRESS, “it is going to make me more suspicious and maybe make me recommend stopping that drug sooner,” she said. Anticonvulsants such as carbamazepine, lamotrigine, and phenobarbital are among the drugs most commonly associated with DRESS.
Toxic erythemas
Patients may present with toxic erythemas, such as fixed drug reactions, erythema multiforme, SJS, and TEN. These drug reactions appear similar on biopsy but have different courses.
A patient with a fixed drug reaction often has a single lesion, and the lesion will occur in the same location every time the patient is exposed to the drug. Patients may develop additional lesions with subsequent exposures. These lesions typically are large, erythematous, well-demarcated plaques with central duskiness. “They can be bullous in the center, and they typically will heal with pigmentation, which is unique to this particular drug reaction,” said Dr. Young. “When it gets more concerning and most important to differentiate is when you get generalized bullous fixed drug eruption.” Generalized bullous fixed drug eruptions mimic and are difficult to clinically distinguish from TEN, which has a much has a much poorer prognosis.
Patients with a fixed drug eruption are not as ill as patients with TEN and tend not to slough their skin to the extent seen with TEN. Interferon gamma, perforin, and Fas ligand have been implicated as mechanisms involved in fixed drug reactions. Unlike in TEN, regulatory T cells are abundant, which may explain why TEN and fixed drug reactions progress differently even though they appear to share pathologic mechanisms, Dr. Young said.
Erythema multiforme generally presents with classic target lesions and little mucosal involvement. Infections, most commonly herpes simplex virus (HSV) 1 and 2, may trigger erythema multiforme. Dr. Young recommends evaluating patients for HSV and checking serologies, even if patients have never had a herpes outbreak. “If you have no evidence for infection, you do have to consider discontinuing a medication,” she said.
Stevens–Johnson syndrome and TEN
SJS and TEN are “the rarest of the severe cutaneous adverse drug reactions” and have “the highest morbidity and mortality,” Dr. Young said. They appear to exist on a continuum where SJS may represent early TEN.
“This is a situation where you expect to see blistering of the skin [and] always mucosal involvement. You need to stop the drug immediately when you suspect this drug reaction,” Dr. Young said.
One reason to distinguish SJS or early TEN from later TEN is that high-dose steroids may play a role in the treatment of SJS or early TEN. “Once you get past about 10% total body surface area, there is good evidence that steroids actually increase morbidity and mortality,” she said.
If the eruption has occurred before, that factor suggests that a diagnosis of erythema multiforme or fixed drug reaction may be more likely than TEN.
An apparent lack of regulatory T cells in TEN could explain why patients with HIV infection are at much higher risk of developing SJS and TEN. Understanding the role that regulatory T cells play in severe drug eruptions may lead to new therapeutic options in the future, Dr. Young said.
Dr. Young had no disclosures.
EXPERT ANALYSIS FROM AES 2018
Minimally invasive ICH lysis safely helps when clot adequately shrinks
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
REPORTING FROM ISC 2019
Key clinical point: Minimally-invasive intracerebral clot lysis was safe and often effective when the residual clot shrank to 15 mL or less.
Major finding: One year after entry, 45% of MISTIE-treated patients and 41% of controls had a modified Rankin Scale score of 0-3.
Study details: MISTIE III, a multicenter, international, randomized trial of 499 patients.
Disclosures: MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
Source: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
Does adherence to a Mediterranean diet reduce the risk of Parkinson’s disease?
Among older adults, adherence to a Mediterranean diet is associated with lower probability of prodromal Parkinson’s disease, according to research published in Movement Disorders.
“Recommending the Mediterranean diet pattern, either to reduce the risk or lessen the effects ... of prodromal Parkinson’s disease, needs to be considered and further explored,” said lead author Maria I. Maraki, PhD, of the department of nutrition and dietetics at Harokopio University in Athens, Greece, and her research colleagues.
Evidence regarding the effect of a Mediterranean diet on Parkinson’s disease risk remains limited, however, and physicians should be cautious in interpreting the data, researchers noted in accompanying editorials.
“There is a puzzling constellation of information and data that cannot be reconciled with a simple model accounting for the role of diet, vascular risk factors, and the neurodegenerative process and mechanisms underlying Parkinson’s disease,” Connie Marras, MD, PhD, and Jose A. Obeso, MD, PhD, said in an editorial. Given Maraki et al.’s findings, “most of us would be glad to accept that such a causal inverse association exists and can therefore be strongly recommended to our patients,” but “further work is needed before definitive conclusions can be reached,” Dr. Marras and Dr. Obeso wrote. Dr. Marras is affiliated with the University Health Network and the University of Toronto. Dr. Obeso is affiliated with University Hospital HM Puerta del Sur, CEU San Pablo University, Móstoles, Spain.
The role of diet
Prior research has suggested that adherence to the Mediterranean diet – characterized by consumption of nonrefined cereals, fruits, vegetables, legumes, potatoes, fish, and olive oil – may be associated with reduced risk of Parkinson’s disease. In addition, studies have found that adherence to the Mediterranean diet may be protective in other diseases, including dementia and cardiovascular disease. Dr. Maraki and her colleagues sought to assess whether adherence to the Mediterranean diet is associated with the likelihood of prodromal Parkinson’s disease or its manifestations. To calculate the probability of prodromal Parkinson’s disease, the investigators used a tool created by the International Parkinson and Movement Disorder Society (MDS) that takes into account baseline risk factors as well as prodromal markers such as constipation and motor slowing.
They analyzed data from 1,731 participants in the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort in Greece. Participants, 41% of whom were male, were aged 65 years or older and did not have Parkinson’s disease. They completed a detailed food frequency questionnaire, and the researchers calculated how closely each participant’s diet adhered to the Mediterranean diet. Diet adherence scores ranged from 0 to 55, with higher scores indicating greater adherence.
The median probability of prodromal Parkinson’s disease was 1.9% (range, 0.2%-96.7%), and the probability was lower among those with greater adherence to the Mediterranean diet. This difference was “driven mostly by nonmotor markers of prodromal Parkinson’s disease,” including depression, constipation, urinary dysfunction, and daytime somnolence, the researchers said. “Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal Parkinson’s disease.” Compared with participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile had an approximately 21% lower probability for prodromal Parkinson’s disease.
Potential confounding
“This study pushes the prodromal criteria into performing a job they were never designed to do,” which presents potential pitfalls, Ronald B. Postuma, MD, of the department of neurology at Montreal General Hospital in Quebec, said in an accompanying editorial.
While the MDS criteria were designed to assess the likelihood that any person over age 50 years is in a state of prodromal Parkinson’s disease, the present study aimed to evaluate whether a single putative risk factor for Parkinson’s disease is associated with the likelihood of its prodromal state.
In addition, the analysis did not include some of the prodromal markers that are part of the MDS criteria, including olfaction, polysomnographic-proven REM sleep behavior disorder, and dopaminergic functional neuroimaging.
“As pointed out by the researchers, many of the risk factors in the prodromal criteria are potentially confounded by factors other than Parkinson’s disease; for example, one could imagine that older people, men, or farmers (with their higher pesticide exposure) are less likely to follow the Mediterranean diet simply because of different cultural lifestyle patterns,” Dr. Postuma said.
It is also possible that the Mediterranean diet affects prodromal markers such as constipation, sleep, or depression without affecting underlying neurodegenerative disease. In any case, the effect sizes observed in the study were small, and there was no evidence that participants who adhered most closely to a Mediterranean diet had less parkinsonism, Dr. Postuma said.
These limitations do not preclude physicians from recommending the diet for other reasons. “Numerous studies, reviews, meta-analyses, and randomized controlled trials consistently rank the Mediterranean diet as among the healthiest diets available,” Dr. Postuma said. “So, one can clearly recommend diets such as these, even if not necessarily for Parkinson’s disease prevention.”
Adding insights
The researchers used a Mediterranean diet score that was developed in a population of adults from metropolitan Athens, “an area not unlike the one in which the score is being applied in the HELIAD study,” Christy C. Tangney, PhD, professor of clinical nutrition and preventive medicine and associate dean for research at Rush University Medical Center, Chicago, said in a separate editorial. As expected, the average Mediterranean diet adherence score in this study was higher than that in the Chicago Health and Aging Project (33.2 vs. 28.2).
“If we can identify differences in diet or lifestyle patterns and risk of this latent phase of Parkinson’s disease neurodegeneration, we may be one step closer to identifying preventive measures,” she said. Follow-up reports from HELIAD and other cohorts may allow researchers to assess how changes in dietary patterns relate to changes in Parkinson’s disease markers, the probability of prodromal Parkinson’s disease, and incident Parkinson’s disease, Dr. Tangney said.
The study authors had no conflicts of interest or financial disclosures. The study was supported by a grant from the Alzheimer’s Association, an ESPA‐EU grant cofunded by the European Social Fund and Greek National resources, and a grant from the Ministry for Health and Social Solidarity (Greece). Dr. Maraki and a coauthor have received financial support from the Greek State Scholarships Foundation. Dr. Tangney and Dr. Postuma had no conflicts of interest.
SOURCE: Maraki MI et al. Mov Disord. 2018 Oct 10. doi: 10.1002/mds.27489.
Among older adults, adherence to a Mediterranean diet is associated with lower probability of prodromal Parkinson’s disease, according to research published in Movement Disorders.
“Recommending the Mediterranean diet pattern, either to reduce the risk or lessen the effects ... of prodromal Parkinson’s disease, needs to be considered and further explored,” said lead author Maria I. Maraki, PhD, of the department of nutrition and dietetics at Harokopio University in Athens, Greece, and her research colleagues.
Evidence regarding the effect of a Mediterranean diet on Parkinson’s disease risk remains limited, however, and physicians should be cautious in interpreting the data, researchers noted in accompanying editorials.
“There is a puzzling constellation of information and data that cannot be reconciled with a simple model accounting for the role of diet, vascular risk factors, and the neurodegenerative process and mechanisms underlying Parkinson’s disease,” Connie Marras, MD, PhD, and Jose A. Obeso, MD, PhD, said in an editorial. Given Maraki et al.’s findings, “most of us would be glad to accept that such a causal inverse association exists and can therefore be strongly recommended to our patients,” but “further work is needed before definitive conclusions can be reached,” Dr. Marras and Dr. Obeso wrote. Dr. Marras is affiliated with the University Health Network and the University of Toronto. Dr. Obeso is affiliated with University Hospital HM Puerta del Sur, CEU San Pablo University, Móstoles, Spain.
The role of diet
Prior research has suggested that adherence to the Mediterranean diet – characterized by consumption of nonrefined cereals, fruits, vegetables, legumes, potatoes, fish, and olive oil – may be associated with reduced risk of Parkinson’s disease. In addition, studies have found that adherence to the Mediterranean diet may be protective in other diseases, including dementia and cardiovascular disease. Dr. Maraki and her colleagues sought to assess whether adherence to the Mediterranean diet is associated with the likelihood of prodromal Parkinson’s disease or its manifestations. To calculate the probability of prodromal Parkinson’s disease, the investigators used a tool created by the International Parkinson and Movement Disorder Society (MDS) that takes into account baseline risk factors as well as prodromal markers such as constipation and motor slowing.
They analyzed data from 1,731 participants in the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort in Greece. Participants, 41% of whom were male, were aged 65 years or older and did not have Parkinson’s disease. They completed a detailed food frequency questionnaire, and the researchers calculated how closely each participant’s diet adhered to the Mediterranean diet. Diet adherence scores ranged from 0 to 55, with higher scores indicating greater adherence.
The median probability of prodromal Parkinson’s disease was 1.9% (range, 0.2%-96.7%), and the probability was lower among those with greater adherence to the Mediterranean diet. This difference was “driven mostly by nonmotor markers of prodromal Parkinson’s disease,” including depression, constipation, urinary dysfunction, and daytime somnolence, the researchers said. “Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal Parkinson’s disease.” Compared with participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile had an approximately 21% lower probability for prodromal Parkinson’s disease.
Potential confounding
“This study pushes the prodromal criteria into performing a job they were never designed to do,” which presents potential pitfalls, Ronald B. Postuma, MD, of the department of neurology at Montreal General Hospital in Quebec, said in an accompanying editorial.
While the MDS criteria were designed to assess the likelihood that any person over age 50 years is in a state of prodromal Parkinson’s disease, the present study aimed to evaluate whether a single putative risk factor for Parkinson’s disease is associated with the likelihood of its prodromal state.
In addition, the analysis did not include some of the prodromal markers that are part of the MDS criteria, including olfaction, polysomnographic-proven REM sleep behavior disorder, and dopaminergic functional neuroimaging.
“As pointed out by the researchers, many of the risk factors in the prodromal criteria are potentially confounded by factors other than Parkinson’s disease; for example, one could imagine that older people, men, or farmers (with their higher pesticide exposure) are less likely to follow the Mediterranean diet simply because of different cultural lifestyle patterns,” Dr. Postuma said.
It is also possible that the Mediterranean diet affects prodromal markers such as constipation, sleep, or depression without affecting underlying neurodegenerative disease. In any case, the effect sizes observed in the study were small, and there was no evidence that participants who adhered most closely to a Mediterranean diet had less parkinsonism, Dr. Postuma said.
These limitations do not preclude physicians from recommending the diet for other reasons. “Numerous studies, reviews, meta-analyses, and randomized controlled trials consistently rank the Mediterranean diet as among the healthiest diets available,” Dr. Postuma said. “So, one can clearly recommend diets such as these, even if not necessarily for Parkinson’s disease prevention.”
Adding insights
The researchers used a Mediterranean diet score that was developed in a population of adults from metropolitan Athens, “an area not unlike the one in which the score is being applied in the HELIAD study,” Christy C. Tangney, PhD, professor of clinical nutrition and preventive medicine and associate dean for research at Rush University Medical Center, Chicago, said in a separate editorial. As expected, the average Mediterranean diet adherence score in this study was higher than that in the Chicago Health and Aging Project (33.2 vs. 28.2).
“If we can identify differences in diet or lifestyle patterns and risk of this latent phase of Parkinson’s disease neurodegeneration, we may be one step closer to identifying preventive measures,” she said. Follow-up reports from HELIAD and other cohorts may allow researchers to assess how changes in dietary patterns relate to changes in Parkinson’s disease markers, the probability of prodromal Parkinson’s disease, and incident Parkinson’s disease, Dr. Tangney said.
The study authors had no conflicts of interest or financial disclosures. The study was supported by a grant from the Alzheimer’s Association, an ESPA‐EU grant cofunded by the European Social Fund and Greek National resources, and a grant from the Ministry for Health and Social Solidarity (Greece). Dr. Maraki and a coauthor have received financial support from the Greek State Scholarships Foundation. Dr. Tangney and Dr. Postuma had no conflicts of interest.
SOURCE: Maraki MI et al. Mov Disord. 2018 Oct 10. doi: 10.1002/mds.27489.
Among older adults, adherence to a Mediterranean diet is associated with lower probability of prodromal Parkinson’s disease, according to research published in Movement Disorders.
“Recommending the Mediterranean diet pattern, either to reduce the risk or lessen the effects ... of prodromal Parkinson’s disease, needs to be considered and further explored,” said lead author Maria I. Maraki, PhD, of the department of nutrition and dietetics at Harokopio University in Athens, Greece, and her research colleagues.
Evidence regarding the effect of a Mediterranean diet on Parkinson’s disease risk remains limited, however, and physicians should be cautious in interpreting the data, researchers noted in accompanying editorials.
“There is a puzzling constellation of information and data that cannot be reconciled with a simple model accounting for the role of diet, vascular risk factors, and the neurodegenerative process and mechanisms underlying Parkinson’s disease,” Connie Marras, MD, PhD, and Jose A. Obeso, MD, PhD, said in an editorial. Given Maraki et al.’s findings, “most of us would be glad to accept that such a causal inverse association exists and can therefore be strongly recommended to our patients,” but “further work is needed before definitive conclusions can be reached,” Dr. Marras and Dr. Obeso wrote. Dr. Marras is affiliated with the University Health Network and the University of Toronto. Dr. Obeso is affiliated with University Hospital HM Puerta del Sur, CEU San Pablo University, Móstoles, Spain.
The role of diet
Prior research has suggested that adherence to the Mediterranean diet – characterized by consumption of nonrefined cereals, fruits, vegetables, legumes, potatoes, fish, and olive oil – may be associated with reduced risk of Parkinson’s disease. In addition, studies have found that adherence to the Mediterranean diet may be protective in other diseases, including dementia and cardiovascular disease. Dr. Maraki and her colleagues sought to assess whether adherence to the Mediterranean diet is associated with the likelihood of prodromal Parkinson’s disease or its manifestations. To calculate the probability of prodromal Parkinson’s disease, the investigators used a tool created by the International Parkinson and Movement Disorder Society (MDS) that takes into account baseline risk factors as well as prodromal markers such as constipation and motor slowing.
They analyzed data from 1,731 participants in the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort in Greece. Participants, 41% of whom were male, were aged 65 years or older and did not have Parkinson’s disease. They completed a detailed food frequency questionnaire, and the researchers calculated how closely each participant’s diet adhered to the Mediterranean diet. Diet adherence scores ranged from 0 to 55, with higher scores indicating greater adherence.
The median probability of prodromal Parkinson’s disease was 1.9% (range, 0.2%-96.7%), and the probability was lower among those with greater adherence to the Mediterranean diet. This difference was “driven mostly by nonmotor markers of prodromal Parkinson’s disease,” including depression, constipation, urinary dysfunction, and daytime somnolence, the researchers said. “Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal Parkinson’s disease.” Compared with participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile had an approximately 21% lower probability for prodromal Parkinson’s disease.
Potential confounding
“This study pushes the prodromal criteria into performing a job they were never designed to do,” which presents potential pitfalls, Ronald B. Postuma, MD, of the department of neurology at Montreal General Hospital in Quebec, said in an accompanying editorial.
While the MDS criteria were designed to assess the likelihood that any person over age 50 years is in a state of prodromal Parkinson’s disease, the present study aimed to evaluate whether a single putative risk factor for Parkinson’s disease is associated with the likelihood of its prodromal state.
In addition, the analysis did not include some of the prodromal markers that are part of the MDS criteria, including olfaction, polysomnographic-proven REM sleep behavior disorder, and dopaminergic functional neuroimaging.
“As pointed out by the researchers, many of the risk factors in the prodromal criteria are potentially confounded by factors other than Parkinson’s disease; for example, one could imagine that older people, men, or farmers (with their higher pesticide exposure) are less likely to follow the Mediterranean diet simply because of different cultural lifestyle patterns,” Dr. Postuma said.
It is also possible that the Mediterranean diet affects prodromal markers such as constipation, sleep, or depression without affecting underlying neurodegenerative disease. In any case, the effect sizes observed in the study were small, and there was no evidence that participants who adhered most closely to a Mediterranean diet had less parkinsonism, Dr. Postuma said.
These limitations do not preclude physicians from recommending the diet for other reasons. “Numerous studies, reviews, meta-analyses, and randomized controlled trials consistently rank the Mediterranean diet as among the healthiest diets available,” Dr. Postuma said. “So, one can clearly recommend diets such as these, even if not necessarily for Parkinson’s disease prevention.”
Adding insights
The researchers used a Mediterranean diet score that was developed in a population of adults from metropolitan Athens, “an area not unlike the one in which the score is being applied in the HELIAD study,” Christy C. Tangney, PhD, professor of clinical nutrition and preventive medicine and associate dean for research at Rush University Medical Center, Chicago, said in a separate editorial. As expected, the average Mediterranean diet adherence score in this study was higher than that in the Chicago Health and Aging Project (33.2 vs. 28.2).
“If we can identify differences in diet or lifestyle patterns and risk of this latent phase of Parkinson’s disease neurodegeneration, we may be one step closer to identifying preventive measures,” she said. Follow-up reports from HELIAD and other cohorts may allow researchers to assess how changes in dietary patterns relate to changes in Parkinson’s disease markers, the probability of prodromal Parkinson’s disease, and incident Parkinson’s disease, Dr. Tangney said.
The study authors had no conflicts of interest or financial disclosures. The study was supported by a grant from the Alzheimer’s Association, an ESPA‐EU grant cofunded by the European Social Fund and Greek National resources, and a grant from the Ministry for Health and Social Solidarity (Greece). Dr. Maraki and a coauthor have received financial support from the Greek State Scholarships Foundation. Dr. Tangney and Dr. Postuma had no conflicts of interest.
SOURCE: Maraki MI et al. Mov Disord. 2018 Oct 10. doi: 10.1002/mds.27489.
FROM MOVEMENT DISORDERS
Key clinical point: Adherence to a Mediterranean diet is associated with lower probability of prodromal Parkinson’s disease.
Major finding: Each 1-unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal Parkinson’s disease.
Study details: A study of 1,731 older adults in the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort in Greece.
Disclosures: The study authors had no conflicts of interest or financial disclosures. The study was supported by a grant from the Alzheimer’s Association, an ESPA‐EU grant cofunded by the European Social Fund and Greek National resources, and a grant from the Ministry for Health and Social Solidarity (Greece). Dr. Maraki and a coauthor have received financial support from the Greek State Scholarships Foundation.
Source: Maraki MI et al. Mov Disord. 2018 Oct 10. doi:10.1002/mds.27489.
Deferoxamine does not improve 90-day outcomes after ICH
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
REPORTING FROM ISC 2019
Key clinical point: Deferoxamine does not improve disability at 90 days after intracranial hemorrhage.
Major finding: Approximately one-third of patients in both treatment groups had a good outcome.
Study details: A multicenter, randomized, double-blind study of 294 participants with intracranial hemorrhage.
Disclosures: The National Institutes of Health and National Institute of Neurological Disorders and Stroke supported this study.
Source: Selim MH et al. ISC 2019, Abstract LB22.
Trial to Test Effectiveness of CBT Phone Sessions for Chronic Pain After TBI
As many as 81.5% of veterans may experience chronic pain, pain that lasts beyond the point of healing and for at least 3 months. It is also particularly prevalent among veterans with traumatic brain injury (TBI) , often accompanied by comorbid conditions. Nearly 90% of veterans with a history of TBI have a psychiatric diagnosis, about 75% have insomnia, and 70% have a pain diagnosis, say researchers from University of Washington and Veterans Administration Puget Sound Health Care System (VAPSHCS).
Cognitive behavioral therapy (CBT) has been shown to help reduce pain, as well as pain-related disability and distress, but no randomized controlled trials (RCT) have examined CBT’s efficacy for pain after TBI in veterans, the researchers say.
In response, the VAPSHCS researchers have designed an RCT to compare telephone-based CBT with telephone-delivered pain education for veterans with TBI and chronic pain. The single-center 2-group trial will enroll up to 160 veterans with TBI to examine the relative efficacy of the interventions on average pain intensity, pain interference, sleep, depression, and life satisfaction.
The participants will be drawn from VAPSHCS, and can be enrolled via clinician referral, electronic health record review, and self-referral. Outcome variables will be collected pre-, mid-, and posttreatment, and 6 months following randomization.
Both interventions will consist of 8 hour-long phone sessions over approximately 8 to 12 weeks, scheduled at times convenient for the participants. Both interventions will also use a participant treatment workbook, with session-specific content to be discussed during the telephone sessions, and audio-recordings to augment material covered. Clinicians will make brief “booster” calls 2, 6, and 10 weeks after the final treatment session.
The trial is innovative, the researchers say, in that it is tailored to veterans, through relatable examples, and to those with TBI, by reducing content and providing multiple methods of engaging with information, as well as using known strategies to help with recall. If effective, the intervention could be disseminated throughout the VHA system, potentially to other personnel who have difficulty accessing specialty pain care.
The trial is registered at ClinicalTrials.gov, protocol NCT01768650.
As many as 81.5% of veterans may experience chronic pain, pain that lasts beyond the point of healing and for at least 3 months. It is also particularly prevalent among veterans with traumatic brain injury (TBI) , often accompanied by comorbid conditions. Nearly 90% of veterans with a history of TBI have a psychiatric diagnosis, about 75% have insomnia, and 70% have a pain diagnosis, say researchers from University of Washington and Veterans Administration Puget Sound Health Care System (VAPSHCS).
Cognitive behavioral therapy (CBT) has been shown to help reduce pain, as well as pain-related disability and distress, but no randomized controlled trials (RCT) have examined CBT’s efficacy for pain after TBI in veterans, the researchers say.
In response, the VAPSHCS researchers have designed an RCT to compare telephone-based CBT with telephone-delivered pain education for veterans with TBI and chronic pain. The single-center 2-group trial will enroll up to 160 veterans with TBI to examine the relative efficacy of the interventions on average pain intensity, pain interference, sleep, depression, and life satisfaction.
The participants will be drawn from VAPSHCS, and can be enrolled via clinician referral, electronic health record review, and self-referral. Outcome variables will be collected pre-, mid-, and posttreatment, and 6 months following randomization.
Both interventions will consist of 8 hour-long phone sessions over approximately 8 to 12 weeks, scheduled at times convenient for the participants. Both interventions will also use a participant treatment workbook, with session-specific content to be discussed during the telephone sessions, and audio-recordings to augment material covered. Clinicians will make brief “booster” calls 2, 6, and 10 weeks after the final treatment session.
The trial is innovative, the researchers say, in that it is tailored to veterans, through relatable examples, and to those with TBI, by reducing content and providing multiple methods of engaging with information, as well as using known strategies to help with recall. If effective, the intervention could be disseminated throughout the VHA system, potentially to other personnel who have difficulty accessing specialty pain care.
The trial is registered at ClinicalTrials.gov, protocol NCT01768650.
As many as 81.5% of veterans may experience chronic pain, pain that lasts beyond the point of healing and for at least 3 months. It is also particularly prevalent among veterans with traumatic brain injury (TBI) , often accompanied by comorbid conditions. Nearly 90% of veterans with a history of TBI have a psychiatric diagnosis, about 75% have insomnia, and 70% have a pain diagnosis, say researchers from University of Washington and Veterans Administration Puget Sound Health Care System (VAPSHCS).
Cognitive behavioral therapy (CBT) has been shown to help reduce pain, as well as pain-related disability and distress, but no randomized controlled trials (RCT) have examined CBT’s efficacy for pain after TBI in veterans, the researchers say.
In response, the VAPSHCS researchers have designed an RCT to compare telephone-based CBT with telephone-delivered pain education for veterans with TBI and chronic pain. The single-center 2-group trial will enroll up to 160 veterans with TBI to examine the relative efficacy of the interventions on average pain intensity, pain interference, sleep, depression, and life satisfaction.
The participants will be drawn from VAPSHCS, and can be enrolled via clinician referral, electronic health record review, and self-referral. Outcome variables will be collected pre-, mid-, and posttreatment, and 6 months following randomization.
Both interventions will consist of 8 hour-long phone sessions over approximately 8 to 12 weeks, scheduled at times convenient for the participants. Both interventions will also use a participant treatment workbook, with session-specific content to be discussed during the telephone sessions, and audio-recordings to augment material covered. Clinicians will make brief “booster” calls 2, 6, and 10 weeks after the final treatment session.
The trial is innovative, the researchers say, in that it is tailored to veterans, through relatable examples, and to those with TBI, by reducing content and providing multiple methods of engaging with information, as well as using known strategies to help with recall. If effective, the intervention could be disseminated throughout the VHA system, potentially to other personnel who have difficulty accessing specialty pain care.
The trial is registered at ClinicalTrials.gov, protocol NCT01768650.
Vaccination and antiviral treatment do not affect stroke risk following shingles
HONOLULU – according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.
The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.
Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.
Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.
To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.
IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).
One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.
The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.
The investigators reported no funding source or disclosures for this study.
SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39
HONOLULU – according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.
The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.
Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.
Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.
To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.
IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).
One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.
The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.
The investigators reported no funding source or disclosures for this study.
SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39
HONOLULU – according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.
The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.
Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.
Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.
To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.
IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).
One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.
The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.
The investigators reported no funding source or disclosures for this study.
SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39
REPORTING FROM ISC 2019
Key clinical point: After a patient develops shingles, prior vaccination or treatment with antiviral medication does not change the risk of acute ischemic stroke.
Major finding: Stroke incidence increased by 61% within 14 days after shingles onset.
Study details: A self-controlled case series of 35,186 Medicare beneficiaries with shingles and acute ischemic stroke.
Disclosures: The authors reported no funding source or disclosures for this study.
Source: Yang Q et al. Circulation. 2019;50(Suppl_1), Abstract 39
International survey probes oxygen’s efficacy for cluster headache
According to the results, triptans also are highly effective, with some side effects. Newer medications deserve further study, the researchers said.
To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, Stuart M. Pearson, a researcher in the department of psychology at the University of West Georgia in Carrollton, and his coauthors analyzed data from the Cluster Headache Questionnaire. Respondents from more than 50 countries completed the online survey; most were from the United States, the United Kingdom, and Canada. The survey included questions about cluster headache diagnostic criteria and medication effectiveness, complications, and access to medications.
In all, 3,251 subjects participated in the questionnaire, and 2,193 respondents met criteria for the study; 1,604 had cluster headache, and 589 had probable cluster headache. Among the respondents with cluster headache, 68.8% were male, 78.0% had episodic cluster headache, and the average age was 46 years. More than half of respondents reported complete or very effective treatment for triptans (54%) and oxygen (also 54%). The proportion of respondents who reported that ergot derivatives, caffeine or energy drinks, and intranasal ketamine were completely or very effective ranged from 14% to 25%. Patients were less likely to report high levels of efficacy for opioids (6%), intranasal capsaicin (5%), and intranasal lidocaine (2%).
Participants experienced few complications from oxygen, with 99% reporting no or minimal physical and medical complications, and 97% reporting no or minimal psychological and emotional complications. Patients also reported few complications from intranasal lidocaine, intranasal ketamine, intranasal capsaicin, and caffeine and energy drinks. For triptans, 74% of respondents reported no or minimal physical and medical complications, and 85% reported no or minimal psychological and emotional complications.
Among the 139 participants with cluster headache who were aged 65 years or older, responses were similar to those for the entire population. In addition, the 589 respondents with probable cluster headache reported similar efficacy data, compared with respondents with a full diagnosis of cluster headache.
“Oxygen in particular had a high rate of complete effectiveness, a low rate of ineffectiveness, and a low rate of physical, medical, emotional, and psychological side effects,” the investigators said. “However, respondents reported that it was difficult to obtain.”
Limited insurance coverage of oxygen may affect access, even though the treatment has a Level A recommendation for the acute treatment of cluster headache in the American Headache Society guidelines, the authors said. Physicians also may pose a barrier. A prior study found that 12% of providers did not prescribe oxygen for cluster headache because they doubted its efficacy or did not know about it. In addition, there may be concerns that the treatment could be a fire hazard in a patient population that has high rates of smoking, the researchers said.
Limitations of the study include the survey’s use of nonvalidated questions, the lack of a formal clinical diagnosis of cluster headache, and the grouping of all triptans, rather than assessing individual triptan medications, such as sumatriptan subcutaneous, alone.
The study received funding from Autonomic Technologies and Clusterbusters. One of the authors has served as a paid consultant to Eli Lilly as a member of the data monitoring committee for clinical trials of galcanezumab for cluster headache and migraine.
This article was updated 3/7/2019.
SOURCE: Pearson SM et al. Headache. 2019 Jan 11. doi: 10.1111/head.13473.
According to the results, triptans also are highly effective, with some side effects. Newer medications deserve further study, the researchers said.
To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, Stuart M. Pearson, a researcher in the department of psychology at the University of West Georgia in Carrollton, and his coauthors analyzed data from the Cluster Headache Questionnaire. Respondents from more than 50 countries completed the online survey; most were from the United States, the United Kingdom, and Canada. The survey included questions about cluster headache diagnostic criteria and medication effectiveness, complications, and access to medications.
In all, 3,251 subjects participated in the questionnaire, and 2,193 respondents met criteria for the study; 1,604 had cluster headache, and 589 had probable cluster headache. Among the respondents with cluster headache, 68.8% were male, 78.0% had episodic cluster headache, and the average age was 46 years. More than half of respondents reported complete or very effective treatment for triptans (54%) and oxygen (also 54%). The proportion of respondents who reported that ergot derivatives, caffeine or energy drinks, and intranasal ketamine were completely or very effective ranged from 14% to 25%. Patients were less likely to report high levels of efficacy for opioids (6%), intranasal capsaicin (5%), and intranasal lidocaine (2%).
Participants experienced few complications from oxygen, with 99% reporting no or minimal physical and medical complications, and 97% reporting no or minimal psychological and emotional complications. Patients also reported few complications from intranasal lidocaine, intranasal ketamine, intranasal capsaicin, and caffeine and energy drinks. For triptans, 74% of respondents reported no or minimal physical and medical complications, and 85% reported no or minimal psychological and emotional complications.
Among the 139 participants with cluster headache who were aged 65 years or older, responses were similar to those for the entire population. In addition, the 589 respondents with probable cluster headache reported similar efficacy data, compared with respondents with a full diagnosis of cluster headache.
“Oxygen in particular had a high rate of complete effectiveness, a low rate of ineffectiveness, and a low rate of physical, medical, emotional, and psychological side effects,” the investigators said. “However, respondents reported that it was difficult to obtain.”
Limited insurance coverage of oxygen may affect access, even though the treatment has a Level A recommendation for the acute treatment of cluster headache in the American Headache Society guidelines, the authors said. Physicians also may pose a barrier. A prior study found that 12% of providers did not prescribe oxygen for cluster headache because they doubted its efficacy or did not know about it. In addition, there may be concerns that the treatment could be a fire hazard in a patient population that has high rates of smoking, the researchers said.
Limitations of the study include the survey’s use of nonvalidated questions, the lack of a formal clinical diagnosis of cluster headache, and the grouping of all triptans, rather than assessing individual triptan medications, such as sumatriptan subcutaneous, alone.
The study received funding from Autonomic Technologies and Clusterbusters. One of the authors has served as a paid consultant to Eli Lilly as a member of the data monitoring committee for clinical trials of galcanezumab for cluster headache and migraine.
This article was updated 3/7/2019.
SOURCE: Pearson SM et al. Headache. 2019 Jan 11. doi: 10.1111/head.13473.
According to the results, triptans also are highly effective, with some side effects. Newer medications deserve further study, the researchers said.
To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, Stuart M. Pearson, a researcher in the department of psychology at the University of West Georgia in Carrollton, and his coauthors analyzed data from the Cluster Headache Questionnaire. Respondents from more than 50 countries completed the online survey; most were from the United States, the United Kingdom, and Canada. The survey included questions about cluster headache diagnostic criteria and medication effectiveness, complications, and access to medications.
In all, 3,251 subjects participated in the questionnaire, and 2,193 respondents met criteria for the study; 1,604 had cluster headache, and 589 had probable cluster headache. Among the respondents with cluster headache, 68.8% were male, 78.0% had episodic cluster headache, and the average age was 46 years. More than half of respondents reported complete or very effective treatment for triptans (54%) and oxygen (also 54%). The proportion of respondents who reported that ergot derivatives, caffeine or energy drinks, and intranasal ketamine were completely or very effective ranged from 14% to 25%. Patients were less likely to report high levels of efficacy for opioids (6%), intranasal capsaicin (5%), and intranasal lidocaine (2%).
Participants experienced few complications from oxygen, with 99% reporting no or minimal physical and medical complications, and 97% reporting no or minimal psychological and emotional complications. Patients also reported few complications from intranasal lidocaine, intranasal ketamine, intranasal capsaicin, and caffeine and energy drinks. For triptans, 74% of respondents reported no or minimal physical and medical complications, and 85% reported no or minimal psychological and emotional complications.
Among the 139 participants with cluster headache who were aged 65 years or older, responses were similar to those for the entire population. In addition, the 589 respondents with probable cluster headache reported similar efficacy data, compared with respondents with a full diagnosis of cluster headache.
“Oxygen in particular had a high rate of complete effectiveness, a low rate of ineffectiveness, and a low rate of physical, medical, emotional, and psychological side effects,” the investigators said. “However, respondents reported that it was difficult to obtain.”
Limited insurance coverage of oxygen may affect access, even though the treatment has a Level A recommendation for the acute treatment of cluster headache in the American Headache Society guidelines, the authors said. Physicians also may pose a barrier. A prior study found that 12% of providers did not prescribe oxygen for cluster headache because they doubted its efficacy or did not know about it. In addition, there may be concerns that the treatment could be a fire hazard in a patient population that has high rates of smoking, the researchers said.
Limitations of the study include the survey’s use of nonvalidated questions, the lack of a formal clinical diagnosis of cluster headache, and the grouping of all triptans, rather than assessing individual triptan medications, such as sumatriptan subcutaneous, alone.
The study received funding from Autonomic Technologies and Clusterbusters. One of the authors has served as a paid consultant to Eli Lilly as a member of the data monitoring committee for clinical trials of galcanezumab for cluster headache and migraine.
This article was updated 3/7/2019.
SOURCE: Pearson SM et al. Headache. 2019 Jan 11. doi: 10.1111/head.13473.
FROM HEADACHE
Key clinical point: Oxygen is a highly effective treatment for cluster headache with few complications.
Major finding: More than half of respondents (54%) reported that triptans and oxygen were completely or very effective.
Study details: Analysis of data from 1,604 people with cluster headache who completed the online Cluster Headache Questionnaire.
Disclosures: The study received funding from Autonomic Technologies and Clusterbusters. One of the authors has served as a paid consultant to Eli Lilly as a member of the data monitoring committee for clinical trials of galcanezumab for cluster headache and migraine.
Source: Pearson SM et al. Headache. 2019 Jan 11. doi: 10.1111/head.13473.
In California, opioids most often prescribed in low-income, mostly white areas
There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.
The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).
“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”
Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.
Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.
During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”
Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.
In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).
While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.
“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.
In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).
Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).
“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.
Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.
The results published by Friedman et al. are a reminder that we can use regional prescribing trends to identify communities most susceptible to the opioid epidemic and give them the resources they need to combat opioid addiction, Vice Adm. Jerome M. Adams, MD, MPH, and Adm. Brett P. Giroir, MD, wrote in a related editorial.
“Discussion of overdose risks and coprescribing of naloxone must become routine if we are to make opioid prescribing safer,” the authors wrote.
Physicians also can help respond to the opioid epidemic outside of prescribing by promoting evidence-based nonopioid and nonpharmaceutical pain treatments, screening their patients for OUD and OUD risks, and acknowledging “that the problem cannot be solved by medical interventions alone.” Individual, environmental, and societal factors also contribute to the opioid epidemic, and physicians are uniquely suited to spearhead efforts aimed at addressing comprehensive opioid misuse.
“Physicians stand out as natural leaders to help solve the crises because of the depth of their knowledge, immediacy of their contact with patients, and relatively high level of respect their profession enjoys,” Dr. Adams and Dr. Giroir wrote. “We thereby call on our nation’s doctors to embrace their roles in the clinic and beyond to help educate communities, bring together stakeholders, and be part of the cultural change to support people living free from addiction.”
Dr. Adams is the 20th surgeon general of the United States at the U.S. Public Health Service and HHS; Dr. Giroir is the 16th U.S. assistant secretary for health at the U.S. Public Health Service and HHS. They reported no relevant conflicts of interest. Their invited commentary accompanied the three related articles in the publication (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7934 ).
The results published by Friedman et al. are a reminder that we can use regional prescribing trends to identify communities most susceptible to the opioid epidemic and give them the resources they need to combat opioid addiction, Vice Adm. Jerome M. Adams, MD, MPH, and Adm. Brett P. Giroir, MD, wrote in a related editorial.
“Discussion of overdose risks and coprescribing of naloxone must become routine if we are to make opioid prescribing safer,” the authors wrote.
Physicians also can help respond to the opioid epidemic outside of prescribing by promoting evidence-based nonopioid and nonpharmaceutical pain treatments, screening their patients for OUD and OUD risks, and acknowledging “that the problem cannot be solved by medical interventions alone.” Individual, environmental, and societal factors also contribute to the opioid epidemic, and physicians are uniquely suited to spearhead efforts aimed at addressing comprehensive opioid misuse.
“Physicians stand out as natural leaders to help solve the crises because of the depth of their knowledge, immediacy of their contact with patients, and relatively high level of respect their profession enjoys,” Dr. Adams and Dr. Giroir wrote. “We thereby call on our nation’s doctors to embrace their roles in the clinic and beyond to help educate communities, bring together stakeholders, and be part of the cultural change to support people living free from addiction.”
Dr. Adams is the 20th surgeon general of the United States at the U.S. Public Health Service and HHS; Dr. Giroir is the 16th U.S. assistant secretary for health at the U.S. Public Health Service and HHS. They reported no relevant conflicts of interest. Their invited commentary accompanied the three related articles in the publication (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7934 ).
The results published by Friedman et al. are a reminder that we can use regional prescribing trends to identify communities most susceptible to the opioid epidemic and give them the resources they need to combat opioid addiction, Vice Adm. Jerome M. Adams, MD, MPH, and Adm. Brett P. Giroir, MD, wrote in a related editorial.
“Discussion of overdose risks and coprescribing of naloxone must become routine if we are to make opioid prescribing safer,” the authors wrote.
Physicians also can help respond to the opioid epidemic outside of prescribing by promoting evidence-based nonopioid and nonpharmaceutical pain treatments, screening their patients for OUD and OUD risks, and acknowledging “that the problem cannot be solved by medical interventions alone.” Individual, environmental, and societal factors also contribute to the opioid epidemic, and physicians are uniquely suited to spearhead efforts aimed at addressing comprehensive opioid misuse.
“Physicians stand out as natural leaders to help solve the crises because of the depth of their knowledge, immediacy of their contact with patients, and relatively high level of respect their profession enjoys,” Dr. Adams and Dr. Giroir wrote. “We thereby call on our nation’s doctors to embrace their roles in the clinic and beyond to help educate communities, bring together stakeholders, and be part of the cultural change to support people living free from addiction.”
Dr. Adams is the 20th surgeon general of the United States at the U.S. Public Health Service and HHS; Dr. Giroir is the 16th U.S. assistant secretary for health at the U.S. Public Health Service and HHS. They reported no relevant conflicts of interest. Their invited commentary accompanied the three related articles in the publication (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7934 ).
There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.
The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).
“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”
Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.
Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.
During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”
Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.
In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).
While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.
“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.
In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).
Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).
“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.
Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.
There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.
The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).
“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”
Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.
Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.
During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”
Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.
In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).
While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.
“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.
In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).
Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).
“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.
Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.
FROM JAMA INTERNAL MEDICINE
Key clinical point: The most common users of opioids according to prescription drug records are residents of mostly low-income, white neighborhoods.
Major finding: Compared with 23.6% of all Californians, 44.2% of individuals in zip codes containing mostly low-income, white residents had at least one opioid prescription each year, compared with 16.1% of individuals in high-income zip codes with the lowest population of white residents.
Study details: An analysis of 29.7 million opioid prescription drug records by race and income in California during 2011-2015.
Disclosures: Dr. Schriger reported support from the Korein Foundation for his time working on the study by Friedman et al. The other authors from Friedman et al. reported no conflicts of interest.
FDA issues warnings to companies selling illegal Alzheimer’s treatments
The Food and Drug Administration has issued warning letters to 12 companies and advisory letters to 5 companies illegally selling more than 58 products claiming to treat Alzheimer’s disease.
The products, many of which are marketed as dietary supplements, are being sold in a variety of forms, including tablets, capsules, and oils. These drugs are either unapproved or mislabeled and claim to prevent, treat, or cure Alzheimer’s disease, as well as a number of other serious diseases and health conditions, in violation of the Federal Food, Drug, and Cosmetic Act.
“Alzheimer’s is a challenging disease that, unfortunately, has no cure. Any products making unproven drug claims could mislead consumers to believe that such therapies exist and keep them from accessing therapies that are known to help support the symptoms of the disease, or worse, as some fraudulent treatments can cause serious or even fatal injuries,” FDA Commissioner Scott Gottlieb, MD, said in a press release.
In an additional statement, Dr. Gottlieb detailed several new strategies for improving the safety and accuracy of dietary supplements, including efforts to more rapidly communicate to the public potential safety issues with dietary supplement products and to establish a flexible regulatory framework that promotes innovation and upholds product safety.
The Food and Drug Administration has issued warning letters to 12 companies and advisory letters to 5 companies illegally selling more than 58 products claiming to treat Alzheimer’s disease.
The products, many of which are marketed as dietary supplements, are being sold in a variety of forms, including tablets, capsules, and oils. These drugs are either unapproved or mislabeled and claim to prevent, treat, or cure Alzheimer’s disease, as well as a number of other serious diseases and health conditions, in violation of the Federal Food, Drug, and Cosmetic Act.
“Alzheimer’s is a challenging disease that, unfortunately, has no cure. Any products making unproven drug claims could mislead consumers to believe that such therapies exist and keep them from accessing therapies that are known to help support the symptoms of the disease, or worse, as some fraudulent treatments can cause serious or even fatal injuries,” FDA Commissioner Scott Gottlieb, MD, said in a press release.
In an additional statement, Dr. Gottlieb detailed several new strategies for improving the safety and accuracy of dietary supplements, including efforts to more rapidly communicate to the public potential safety issues with dietary supplement products and to establish a flexible regulatory framework that promotes innovation and upholds product safety.
The Food and Drug Administration has issued warning letters to 12 companies and advisory letters to 5 companies illegally selling more than 58 products claiming to treat Alzheimer’s disease.
The products, many of which are marketed as dietary supplements, are being sold in a variety of forms, including tablets, capsules, and oils. These drugs are either unapproved or mislabeled and claim to prevent, treat, or cure Alzheimer’s disease, as well as a number of other serious diseases and health conditions, in violation of the Federal Food, Drug, and Cosmetic Act.
“Alzheimer’s is a challenging disease that, unfortunately, has no cure. Any products making unproven drug claims could mislead consumers to believe that such therapies exist and keep them from accessing therapies that are known to help support the symptoms of the disease, or worse, as some fraudulent treatments can cause serious or even fatal injuries,” FDA Commissioner Scott Gottlieb, MD, said in a press release.
In an additional statement, Dr. Gottlieb detailed several new strategies for improving the safety and accuracy of dietary supplements, including efforts to more rapidly communicate to the public potential safety issues with dietary supplement products and to establish a flexible regulatory framework that promotes innovation and upholds product safety.
Most U.S. tPA-eligible stroke patients now get treated within an hour
HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and .
By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.
The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.
“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”
During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.
The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.
The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.
With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.
The Target: Stroke and Get With The Guidelines-Stroke programs should be commended for the very impressive achievements they have made in improved delivery of thrombolytic therapy to acute ischemic stroke patients. What’s happened over the past decade in the speed of delivery of tissue plasminogen activator for treating U.S. stroke patients has been a real success story.
Programs like Get With The Guidelines and Target: Stroke have proven their value, but a significant barrier remains to bringing this program to all U.S. stroke patients and to all U.S. hospitals that treat stroke patients. That barrier is resources. Participating hospitals need to meet certain data-collection standards, but some U.S. hospitals do not have the resources to do this.
Bruce Ovbiagele, MD , is a neurologist and chief of staff for the San Francisco Veterans Affairs Health Care System. He had no disclosures. He made these comments in an interview.
The Target: Stroke and Get With The Guidelines-Stroke programs should be commended for the very impressive achievements they have made in improved delivery of thrombolytic therapy to acute ischemic stroke patients. What’s happened over the past decade in the speed of delivery of tissue plasminogen activator for treating U.S. stroke patients has been a real success story.
Programs like Get With The Guidelines and Target: Stroke have proven their value, but a significant barrier remains to bringing this program to all U.S. stroke patients and to all U.S. hospitals that treat stroke patients. That barrier is resources. Participating hospitals need to meet certain data-collection standards, but some U.S. hospitals do not have the resources to do this.
Bruce Ovbiagele, MD , is a neurologist and chief of staff for the San Francisco Veterans Affairs Health Care System. He had no disclosures. He made these comments in an interview.
The Target: Stroke and Get With The Guidelines-Stroke programs should be commended for the very impressive achievements they have made in improved delivery of thrombolytic therapy to acute ischemic stroke patients. What’s happened over the past decade in the speed of delivery of tissue plasminogen activator for treating U.S. stroke patients has been a real success story.
Programs like Get With The Guidelines and Target: Stroke have proven their value, but a significant barrier remains to bringing this program to all U.S. stroke patients and to all U.S. hospitals that treat stroke patients. That barrier is resources. Participating hospitals need to meet certain data-collection standards, but some U.S. hospitals do not have the resources to do this.
Bruce Ovbiagele, MD , is a neurologist and chief of staff for the San Francisco Veterans Affairs Health Care System. He had no disclosures. He made these comments in an interview.
HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and .
By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.
The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.
“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”
During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.
The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.
The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.
With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.
HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and .
By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.
The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.
“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”
During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.
The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.
The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.
With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.
REPORTING FROM ISC 2019
Key clinical point: In late 2018, the Target: Stroke program met its phase 2 goal for timely delivery of thrombolytic therapy to acute ischemic stroke patients.
Major finding: In September 2018, 75% of eligible stroke patients underwent thrombolysis within 60 minutes of hospital arrival, and 52% within 45 minutes.
Study details: Review of data collected from 154,221 U.S. stroke patients treated with thrombolysis during 2003-2018.
Disclosures: Target: Stroke has received funding from Boehringer Ingelheim, Janssen, Bristol-Myers Squibb/Sanofi, and Merck. Dr. Fonarow had no relevant disclosures.
Source: Fonarow GC et al. ISC 2019, Abstract LBP9.