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Upper GI bleed guidelines say endoscopy within 24 hours of bleed
Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.
The guidelines were published in the American Journal of Gastroenterology.
One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.
A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.
“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.
Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.
That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.
Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.
This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).
“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.
There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.
Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.
Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.
The guidelines were published in the American Journal of Gastroenterology.
One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.
A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.
“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.
Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.
That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.
Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.
This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).
“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.
There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.
Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.
Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.
The guidelines were published in the American Journal of Gastroenterology.
One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.
A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.
“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.
Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.
That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.
Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.
This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).
“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.
There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.
Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Better ways to handle in-hospital conflicts
Imagine a hospitalist, part of a group with 35 hospitalists, is in her second year of practice and is caring for a 55-year-old woman with a history of congestive heart failure and cirrhosis from hepatitis C due to heroin use. The patient was hospitalized with acute back pain and found to have vertebral osteomyelitis confirmed on MRI.
The hospitalist calls a surgeon to get a biopsy so that antibiotic therapy can be chosen. The surgeon says it’s the second time the patient has been hospitalized for this condition, and asks, “Why do you need me to see this patient?” He says the hospitalist should just give IV antibiotics and consult infectious disease.
The hospitalist says, “The patient needs this biopsy. I’ll just call your chair.”
In the course of a busy day, conflicts arise all the time in the hospital – between clinicians, between patients and clinicians, and as internal battles when clinicians face uncertain situations. There are ways to make these conflicts less tense and more in tune with patient care, panelists said recently during a session at SHM Converge, the annual conference of the Society of Hospital Medicine.
In the case of vertebral osteomyelitis, for instance, the hospitalist was using a “position-based” strategy to deal with the conflict with the surgeon – she came in knowing she wanted a biopsy – rather than an “interest-based” strategy, or what is in the patient’s interest, said Patrick Rendon, MD, FHM, assistant professor in the hospital medicine division at the University of New Mexico, Albuquerque.
“What we really need to do is realign the thinking from both the hospitalist as well as the consult perspective,” Dr. Rendon said. “It is not us versus the consultant or the consult versus us. It should be both, together, versus the problem.”
Instead of saying something like, “I need this biopsy,” it might be better to ask for an evaluation, he said.
Handling conflicts better can improve patient care but can also benefit the clinicians themselves. While hospitalists say they routinely experience “pushback” when making a request of a consultant, they also say that they prefer to receive instruction when consulting about a case. Dr. Rendon said that hospitalists also say they want this teaching done “in the right way,” and consultants routinely say that their instruction, when they give it, is often met with resistance.
“The idea here is to open up perspectives,” Dr. Rendon said.
Emily Gottenborg, MD, hospitalist and assistant professor of medicine at the University of Colorado, discussed the case of an intern caring for a patient who says something offensive.
Conflicts, she said, come in all sorts – intimidation, harassment, bias. And they can be based on race, gender, disability, and hierarchy, she said. When on the receiving end of offensive remarks from patients, it’s important for a clinician to set boundaries and quickly move on, with responses such as, “I care about you as a person, but I will not tolerate offensive behavior. Let’s focus on how I can help you today.”
“Practice that behavior so that you have a script in your mind and then use it when needed so that you can nip this behavior in the bud,” Dr. Gottenborg said.
In her hypothetical case, the intern asks for help from her program, and monthly morbidity and mortality workshops on bias and harassment are scheduled. She also receives counseling, and faculty and staff receive discrimination and bias training. Getting help from the institution can help systematically reduce these problems, Dr. Gottenborg said.
Ernie Esquivel, MD, SFHM, hospitalist and assistant professor of clinical medicine at Weill Cornell Medicine, New York, said internal conflicts test physicians routinely – and this has been especially true during the COVID-19 pandemic, in which urgent clinical situations arose with no clear answers.
“In the past year, physicians have experienced an incredible amount of anxiety and stress,” he said. “Tolerating uncertainty is probably one of the most mature skills that we need to learn as a physician.”
The culture of medicine, to a large degree, promotes the opposite tendency: value is placed on nailing down the diagnosis or achieving certainty. Confidence levels of physicians tend not to waver, even in the face of difficult cases full of uncertainty, Dr. Esquivel said.
He urged physicians to practice “deliberate clinical inertia” – to resist a quick response and to think more deeply and systematically about a situation. To show the importance of this, he asks residents to rank diagnoses, using sticky notes, as information about a case is provided. By the fourth round, when much more information is available, the diagnoses have changed dramatically.
Dr. Esquivel suggested physicians switch from thinking in terms of “diagnoses” to thinking in terms of “hypotheses.” That approach can help clinicians tolerate uncertainty, because it reinforces the idea that they are dealing with an “iterative process.”
“There may not be one diagnosis to consider,” he said, “but several in play at once.”
A version of this article first appeared on Medscape.com.
Imagine a hospitalist, part of a group with 35 hospitalists, is in her second year of practice and is caring for a 55-year-old woman with a history of congestive heart failure and cirrhosis from hepatitis C due to heroin use. The patient was hospitalized with acute back pain and found to have vertebral osteomyelitis confirmed on MRI.
The hospitalist calls a surgeon to get a biopsy so that antibiotic therapy can be chosen. The surgeon says it’s the second time the patient has been hospitalized for this condition, and asks, “Why do you need me to see this patient?” He says the hospitalist should just give IV antibiotics and consult infectious disease.
The hospitalist says, “The patient needs this biopsy. I’ll just call your chair.”
In the course of a busy day, conflicts arise all the time in the hospital – between clinicians, between patients and clinicians, and as internal battles when clinicians face uncertain situations. There are ways to make these conflicts less tense and more in tune with patient care, panelists said recently during a session at SHM Converge, the annual conference of the Society of Hospital Medicine.
In the case of vertebral osteomyelitis, for instance, the hospitalist was using a “position-based” strategy to deal with the conflict with the surgeon – she came in knowing she wanted a biopsy – rather than an “interest-based” strategy, or what is in the patient’s interest, said Patrick Rendon, MD, FHM, assistant professor in the hospital medicine division at the University of New Mexico, Albuquerque.
“What we really need to do is realign the thinking from both the hospitalist as well as the consult perspective,” Dr. Rendon said. “It is not us versus the consultant or the consult versus us. It should be both, together, versus the problem.”
Instead of saying something like, “I need this biopsy,” it might be better to ask for an evaluation, he said.
Handling conflicts better can improve patient care but can also benefit the clinicians themselves. While hospitalists say they routinely experience “pushback” when making a request of a consultant, they also say that they prefer to receive instruction when consulting about a case. Dr. Rendon said that hospitalists also say they want this teaching done “in the right way,” and consultants routinely say that their instruction, when they give it, is often met with resistance.
“The idea here is to open up perspectives,” Dr. Rendon said.
Emily Gottenborg, MD, hospitalist and assistant professor of medicine at the University of Colorado, discussed the case of an intern caring for a patient who says something offensive.
Conflicts, she said, come in all sorts – intimidation, harassment, bias. And they can be based on race, gender, disability, and hierarchy, she said. When on the receiving end of offensive remarks from patients, it’s important for a clinician to set boundaries and quickly move on, with responses such as, “I care about you as a person, but I will not tolerate offensive behavior. Let’s focus on how I can help you today.”
“Practice that behavior so that you have a script in your mind and then use it when needed so that you can nip this behavior in the bud,” Dr. Gottenborg said.
In her hypothetical case, the intern asks for help from her program, and monthly morbidity and mortality workshops on bias and harassment are scheduled. She also receives counseling, and faculty and staff receive discrimination and bias training. Getting help from the institution can help systematically reduce these problems, Dr. Gottenborg said.
Ernie Esquivel, MD, SFHM, hospitalist and assistant professor of clinical medicine at Weill Cornell Medicine, New York, said internal conflicts test physicians routinely – and this has been especially true during the COVID-19 pandemic, in which urgent clinical situations arose with no clear answers.
“In the past year, physicians have experienced an incredible amount of anxiety and stress,” he said. “Tolerating uncertainty is probably one of the most mature skills that we need to learn as a physician.”
The culture of medicine, to a large degree, promotes the opposite tendency: value is placed on nailing down the diagnosis or achieving certainty. Confidence levels of physicians tend not to waver, even in the face of difficult cases full of uncertainty, Dr. Esquivel said.
He urged physicians to practice “deliberate clinical inertia” – to resist a quick response and to think more deeply and systematically about a situation. To show the importance of this, he asks residents to rank diagnoses, using sticky notes, as information about a case is provided. By the fourth round, when much more information is available, the diagnoses have changed dramatically.
Dr. Esquivel suggested physicians switch from thinking in terms of “diagnoses” to thinking in terms of “hypotheses.” That approach can help clinicians tolerate uncertainty, because it reinforces the idea that they are dealing with an “iterative process.”
“There may not be one diagnosis to consider,” he said, “but several in play at once.”
A version of this article first appeared on Medscape.com.
Imagine a hospitalist, part of a group with 35 hospitalists, is in her second year of practice and is caring for a 55-year-old woman with a history of congestive heart failure and cirrhosis from hepatitis C due to heroin use. The patient was hospitalized with acute back pain and found to have vertebral osteomyelitis confirmed on MRI.
The hospitalist calls a surgeon to get a biopsy so that antibiotic therapy can be chosen. The surgeon says it’s the second time the patient has been hospitalized for this condition, and asks, “Why do you need me to see this patient?” He says the hospitalist should just give IV antibiotics and consult infectious disease.
The hospitalist says, “The patient needs this biopsy. I’ll just call your chair.”
In the course of a busy day, conflicts arise all the time in the hospital – between clinicians, between patients and clinicians, and as internal battles when clinicians face uncertain situations. There are ways to make these conflicts less tense and more in tune with patient care, panelists said recently during a session at SHM Converge, the annual conference of the Society of Hospital Medicine.
In the case of vertebral osteomyelitis, for instance, the hospitalist was using a “position-based” strategy to deal with the conflict with the surgeon – she came in knowing she wanted a biopsy – rather than an “interest-based” strategy, or what is in the patient’s interest, said Patrick Rendon, MD, FHM, assistant professor in the hospital medicine division at the University of New Mexico, Albuquerque.
“What we really need to do is realign the thinking from both the hospitalist as well as the consult perspective,” Dr. Rendon said. “It is not us versus the consultant or the consult versus us. It should be both, together, versus the problem.”
Instead of saying something like, “I need this biopsy,” it might be better to ask for an evaluation, he said.
Handling conflicts better can improve patient care but can also benefit the clinicians themselves. While hospitalists say they routinely experience “pushback” when making a request of a consultant, they also say that they prefer to receive instruction when consulting about a case. Dr. Rendon said that hospitalists also say they want this teaching done “in the right way,” and consultants routinely say that their instruction, when they give it, is often met with resistance.
“The idea here is to open up perspectives,” Dr. Rendon said.
Emily Gottenborg, MD, hospitalist and assistant professor of medicine at the University of Colorado, discussed the case of an intern caring for a patient who says something offensive.
Conflicts, she said, come in all sorts – intimidation, harassment, bias. And they can be based on race, gender, disability, and hierarchy, she said. When on the receiving end of offensive remarks from patients, it’s important for a clinician to set boundaries and quickly move on, with responses such as, “I care about you as a person, but I will not tolerate offensive behavior. Let’s focus on how I can help you today.”
“Practice that behavior so that you have a script in your mind and then use it when needed so that you can nip this behavior in the bud,” Dr. Gottenborg said.
In her hypothetical case, the intern asks for help from her program, and monthly morbidity and mortality workshops on bias and harassment are scheduled. She also receives counseling, and faculty and staff receive discrimination and bias training. Getting help from the institution can help systematically reduce these problems, Dr. Gottenborg said.
Ernie Esquivel, MD, SFHM, hospitalist and assistant professor of clinical medicine at Weill Cornell Medicine, New York, said internal conflicts test physicians routinely – and this has been especially true during the COVID-19 pandemic, in which urgent clinical situations arose with no clear answers.
“In the past year, physicians have experienced an incredible amount of anxiety and stress,” he said. “Tolerating uncertainty is probably one of the most mature skills that we need to learn as a physician.”
The culture of medicine, to a large degree, promotes the opposite tendency: value is placed on nailing down the diagnosis or achieving certainty. Confidence levels of physicians tend not to waver, even in the face of difficult cases full of uncertainty, Dr. Esquivel said.
He urged physicians to practice “deliberate clinical inertia” – to resist a quick response and to think more deeply and systematically about a situation. To show the importance of this, he asks residents to rank diagnoses, using sticky notes, as information about a case is provided. By the fourth round, when much more information is available, the diagnoses have changed dramatically.
Dr. Esquivel suggested physicians switch from thinking in terms of “diagnoses” to thinking in terms of “hypotheses.” That approach can help clinicians tolerate uncertainty, because it reinforces the idea that they are dealing with an “iterative process.”
“There may not be one diagnosis to consider,” he said, “but several in play at once.”
A version of this article first appeared on Medscape.com.
FROM SHM CONVERGE 2021
Deep brain stimulation is effective over the long haul
, new research indicates.
“Subthalamic nucleus stimulation is a well recognized treatment used for improving motor conditions and quality of life in people with Parkinson’s disease. Our study, for the first time, supports its efficacy in the very long term – 15 years after surgery and 25 years since the Parkinson’s disease diagnosis,” said Elena Moro, MD, PhD, Grenoble Alpes University, Grenoble, France.
“This information is relevant for physicians, patients, and their families when they need to decide about the surgical option to deal with Parkinson’s disease,” said Dr. Moro.
The study was published online June 2 in Neurology.
‘Don’t delay’
The findings are based on 51 patients with Parkinson’s disease who underwent treatment with bilateral STN-DBS for an average of 17 years (range, 15-24 years). Their average age at diagnosis was 40 years, and the average age at device implantation was 51 years.
The results demonstrate that STN-DBS continues to be effective for motor complications for longer than 15 years, reducing time spent with dyskinesia by 75% and time spent in the off-state by 58.7%. This is similar to the amount of improvement seen 1 year after surgery.
Doses of dopaminergic medications continued to be low at long-term follow-up; dosing was reduced by 50.6% compared with baseline.
There was also continued improvement in quality of life. Scores on the Parkinson’s Disease Quality of Life Questionnaire in the very long term were 13.8% better compared with baseline.
“Few and mostly manageable device-related adverse events were observed during the follow-up,” the authors reported in their article.
“Deep brain stimulation is already recommended when a patient’s conditions are not optimized by medical treatment. Patients with Parkinson’s disease without dementia and in good general health conditions are the best candidates for this surgery,” said Dr. Moro.
“Taking into account our results and the data available in the literature, DBS surgery should not be delayed when motor conditions and quality of life decline despite medical treatment, if patients meet the inclusion criteria,” she added.
A revolutionary treatment
The authors of an accompanying editorial say these results, which indicate better motor outcomes with less medication, “reinforce why STN-DBS has revolutionized treatment for advanced Parkinson’s disease.”
Kelvin Chou, MD, of the University of Michigan, Ann Arbor, and David Charles, MD, of Vanderbilt University, Nashville, Tenn., pointed out that longer disease duration is associated with an increase in the likelihood of cognitive impairment and psychosis, both of which are risk factors for nursing home placement, and they limit the ability to use dopaminergic medications.
Although many of the patients in this cohort experienced hallucinations and psychosis over the long follow-up period, “one can imagine that the number and severity would be higher without DBS therapy,” they wrote.
Key caveats, said Dr. Chou and Dr. Charles, are that the results are based on a highly selected cohort and that the patients were managed by experts in the field of movement disorders and DBS.
Additionally, the patients’ conditions were highly responsive to levodopa; there was a 75.3% baseline improvement in Unified Parkinson’s Disease Rating Scale motor scores from the off-state to the on-state. In general, most DBS centers consider a levodopa response of approximately 30% as an acceptable cutoff for moving forward with STN-DBS, they noted.
Despite these caveats and limitations, the results of the study are important with respect to counseling potential candidates for DBS, Dr. Chou and Dr. Charles said.
“A common question that patients have is, ‘How long do the benefits of DBS last?’ We can now reassure them that, at least for STN-DBS, improvement in motor complications lasts beyond 15 years and is often accompanied by improvement in quality of life. In other words, with STN-DBS, we can uncomplicate their motor complications for the long haul,” the editorial writers concluded.
The research had no targeted funding. Moro has received honoraria from Medtronic and Abbott for consulting and lecturing and an educational grant from Boston and Newronika. A complete list of disclosures is available with the original articles.
A version of this article first appeared on Medscape.com.
, new research indicates.
“Subthalamic nucleus stimulation is a well recognized treatment used for improving motor conditions and quality of life in people with Parkinson’s disease. Our study, for the first time, supports its efficacy in the very long term – 15 years after surgery and 25 years since the Parkinson’s disease diagnosis,” said Elena Moro, MD, PhD, Grenoble Alpes University, Grenoble, France.
“This information is relevant for physicians, patients, and their families when they need to decide about the surgical option to deal with Parkinson’s disease,” said Dr. Moro.
The study was published online June 2 in Neurology.
‘Don’t delay’
The findings are based on 51 patients with Parkinson’s disease who underwent treatment with bilateral STN-DBS for an average of 17 years (range, 15-24 years). Their average age at diagnosis was 40 years, and the average age at device implantation was 51 years.
The results demonstrate that STN-DBS continues to be effective for motor complications for longer than 15 years, reducing time spent with dyskinesia by 75% and time spent in the off-state by 58.7%. This is similar to the amount of improvement seen 1 year after surgery.
Doses of dopaminergic medications continued to be low at long-term follow-up; dosing was reduced by 50.6% compared with baseline.
There was also continued improvement in quality of life. Scores on the Parkinson’s Disease Quality of Life Questionnaire in the very long term were 13.8% better compared with baseline.
“Few and mostly manageable device-related adverse events were observed during the follow-up,” the authors reported in their article.
“Deep brain stimulation is already recommended when a patient’s conditions are not optimized by medical treatment. Patients with Parkinson’s disease without dementia and in good general health conditions are the best candidates for this surgery,” said Dr. Moro.
“Taking into account our results and the data available in the literature, DBS surgery should not be delayed when motor conditions and quality of life decline despite medical treatment, if patients meet the inclusion criteria,” she added.
A revolutionary treatment
The authors of an accompanying editorial say these results, which indicate better motor outcomes with less medication, “reinforce why STN-DBS has revolutionized treatment for advanced Parkinson’s disease.”
Kelvin Chou, MD, of the University of Michigan, Ann Arbor, and David Charles, MD, of Vanderbilt University, Nashville, Tenn., pointed out that longer disease duration is associated with an increase in the likelihood of cognitive impairment and psychosis, both of which are risk factors for nursing home placement, and they limit the ability to use dopaminergic medications.
Although many of the patients in this cohort experienced hallucinations and psychosis over the long follow-up period, “one can imagine that the number and severity would be higher without DBS therapy,” they wrote.
Key caveats, said Dr. Chou and Dr. Charles, are that the results are based on a highly selected cohort and that the patients were managed by experts in the field of movement disorders and DBS.
Additionally, the patients’ conditions were highly responsive to levodopa; there was a 75.3% baseline improvement in Unified Parkinson’s Disease Rating Scale motor scores from the off-state to the on-state. In general, most DBS centers consider a levodopa response of approximately 30% as an acceptable cutoff for moving forward with STN-DBS, they noted.
Despite these caveats and limitations, the results of the study are important with respect to counseling potential candidates for DBS, Dr. Chou and Dr. Charles said.
“A common question that patients have is, ‘How long do the benefits of DBS last?’ We can now reassure them that, at least for STN-DBS, improvement in motor complications lasts beyond 15 years and is often accompanied by improvement in quality of life. In other words, with STN-DBS, we can uncomplicate their motor complications for the long haul,” the editorial writers concluded.
The research had no targeted funding. Moro has received honoraria from Medtronic and Abbott for consulting and lecturing and an educational grant from Boston and Newronika. A complete list of disclosures is available with the original articles.
A version of this article first appeared on Medscape.com.
, new research indicates.
“Subthalamic nucleus stimulation is a well recognized treatment used for improving motor conditions and quality of life in people with Parkinson’s disease. Our study, for the first time, supports its efficacy in the very long term – 15 years after surgery and 25 years since the Parkinson’s disease diagnosis,” said Elena Moro, MD, PhD, Grenoble Alpes University, Grenoble, France.
“This information is relevant for physicians, patients, and their families when they need to decide about the surgical option to deal with Parkinson’s disease,” said Dr. Moro.
The study was published online June 2 in Neurology.
‘Don’t delay’
The findings are based on 51 patients with Parkinson’s disease who underwent treatment with bilateral STN-DBS for an average of 17 years (range, 15-24 years). Their average age at diagnosis was 40 years, and the average age at device implantation was 51 years.
The results demonstrate that STN-DBS continues to be effective for motor complications for longer than 15 years, reducing time spent with dyskinesia by 75% and time spent in the off-state by 58.7%. This is similar to the amount of improvement seen 1 year after surgery.
Doses of dopaminergic medications continued to be low at long-term follow-up; dosing was reduced by 50.6% compared with baseline.
There was also continued improvement in quality of life. Scores on the Parkinson’s Disease Quality of Life Questionnaire in the very long term were 13.8% better compared with baseline.
“Few and mostly manageable device-related adverse events were observed during the follow-up,” the authors reported in their article.
“Deep brain stimulation is already recommended when a patient’s conditions are not optimized by medical treatment. Patients with Parkinson’s disease without dementia and in good general health conditions are the best candidates for this surgery,” said Dr. Moro.
“Taking into account our results and the data available in the literature, DBS surgery should not be delayed when motor conditions and quality of life decline despite medical treatment, if patients meet the inclusion criteria,” she added.
A revolutionary treatment
The authors of an accompanying editorial say these results, which indicate better motor outcomes with less medication, “reinforce why STN-DBS has revolutionized treatment for advanced Parkinson’s disease.”
Kelvin Chou, MD, of the University of Michigan, Ann Arbor, and David Charles, MD, of Vanderbilt University, Nashville, Tenn., pointed out that longer disease duration is associated with an increase in the likelihood of cognitive impairment and psychosis, both of which are risk factors for nursing home placement, and they limit the ability to use dopaminergic medications.
Although many of the patients in this cohort experienced hallucinations and psychosis over the long follow-up period, “one can imagine that the number and severity would be higher without DBS therapy,” they wrote.
Key caveats, said Dr. Chou and Dr. Charles, are that the results are based on a highly selected cohort and that the patients were managed by experts in the field of movement disorders and DBS.
Additionally, the patients’ conditions were highly responsive to levodopa; there was a 75.3% baseline improvement in Unified Parkinson’s Disease Rating Scale motor scores from the off-state to the on-state. In general, most DBS centers consider a levodopa response of approximately 30% as an acceptable cutoff for moving forward with STN-DBS, they noted.
Despite these caveats and limitations, the results of the study are important with respect to counseling potential candidates for DBS, Dr. Chou and Dr. Charles said.
“A common question that patients have is, ‘How long do the benefits of DBS last?’ We can now reassure them that, at least for STN-DBS, improvement in motor complications lasts beyond 15 years and is often accompanied by improvement in quality of life. In other words, with STN-DBS, we can uncomplicate their motor complications for the long haul,” the editorial writers concluded.
The research had no targeted funding. Moro has received honoraria from Medtronic and Abbott for consulting and lecturing and an educational grant from Boston and Newronika. A complete list of disclosures is available with the original articles.
A version of this article first appeared on Medscape.com.
From Neurology
Pregnant women with PsA at risk for adverse maternal outcomes
Key clinical point: Psoriatic arthritis (PsA) adversely affected maternal outcomes in pregnant women; however, there was no adverse effect on neonatal outcomes.
Major finding: The risk for cesarean delivery (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.27-1.66), preterm birth (OR, 1.48; 95% CI, 1.24-1.78), preeclampsia (OR, 1.45; 95% CI, 1.13-1.85), and gestational hypertension (OR, 1.49; 95% CI, 1.09-2.06) was significantly higher in pregnant women with PsA vs. general population. However, no statistically increased risk for fetal complications was observed in women with PsA.
Study details: Findings are from a meta-analysis of 16 observational studies including more than 46,909 cases of psoriasis/PsA with over 53,541 pregnancies and more than 4,771,352 healthy controls with over 8,044,996 pregnancies.
Disclosures: This study was funded by the National Natural Science Foundation of China. All authors declared no conflicts of interest.
Source: Xie W et al. Rheumatology (Oxford). 2021 Apr 20. doi: 10.1093/rheumatology/keab357.
Key clinical point: Psoriatic arthritis (PsA) adversely affected maternal outcomes in pregnant women; however, there was no adverse effect on neonatal outcomes.
Major finding: The risk for cesarean delivery (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.27-1.66), preterm birth (OR, 1.48; 95% CI, 1.24-1.78), preeclampsia (OR, 1.45; 95% CI, 1.13-1.85), and gestational hypertension (OR, 1.49; 95% CI, 1.09-2.06) was significantly higher in pregnant women with PsA vs. general population. However, no statistically increased risk for fetal complications was observed in women with PsA.
Study details: Findings are from a meta-analysis of 16 observational studies including more than 46,909 cases of psoriasis/PsA with over 53,541 pregnancies and more than 4,771,352 healthy controls with over 8,044,996 pregnancies.
Disclosures: This study was funded by the National Natural Science Foundation of China. All authors declared no conflicts of interest.
Source: Xie W et al. Rheumatology (Oxford). 2021 Apr 20. doi: 10.1093/rheumatology/keab357.
Key clinical point: Psoriatic arthritis (PsA) adversely affected maternal outcomes in pregnant women; however, there was no adverse effect on neonatal outcomes.
Major finding: The risk for cesarean delivery (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.27-1.66), preterm birth (OR, 1.48; 95% CI, 1.24-1.78), preeclampsia (OR, 1.45; 95% CI, 1.13-1.85), and gestational hypertension (OR, 1.49; 95% CI, 1.09-2.06) was significantly higher in pregnant women with PsA vs. general population. However, no statistically increased risk for fetal complications was observed in women with PsA.
Study details: Findings are from a meta-analysis of 16 observational studies including more than 46,909 cases of psoriasis/PsA with over 53,541 pregnancies and more than 4,771,352 healthy controls with over 8,044,996 pregnancies.
Disclosures: This study was funded by the National Natural Science Foundation of China. All authors declared no conflicts of interest.
Source: Xie W et al. Rheumatology (Oxford). 2021 Apr 20. doi: 10.1093/rheumatology/keab357.
Tender joints in active PsA poorly reflect inflammation indicated by ultrasound and MRI
Key clinical point: Joint tenderness showed poor association with imaging signs of inflammation in patients with psoriatic arthritis (PsA).
Major finding: Tender or swollen joint count showed no significant correlations with imaging inflammation sum-scores. Negligible to weak correlation (rho, −0.31 to 0.38) was observed between imaging inflammation sum-scores and the respective clinical joint counts, patient-reported outcomes, and composite scores with no consistently significant results.
Study details: This was a cross-sectional study of 41 patients with active PsA assessed by ultrasound and magnetic resonance imaging (MRI) for joint swelling.
Disclosures: The study was financially supported by AbbVie. Some of the authors reported receiving research grants, consulting fees, and speaker fees from various sources including AbbVie.
Source: Felbo SK et al. Rheumatology (Oxford). 2021 Apr 24. doi: 10.1093/rheumatology/keab384.
Key clinical point: Joint tenderness showed poor association with imaging signs of inflammation in patients with psoriatic arthritis (PsA).
Major finding: Tender or swollen joint count showed no significant correlations with imaging inflammation sum-scores. Negligible to weak correlation (rho, −0.31 to 0.38) was observed between imaging inflammation sum-scores and the respective clinical joint counts, patient-reported outcomes, and composite scores with no consistently significant results.
Study details: This was a cross-sectional study of 41 patients with active PsA assessed by ultrasound and magnetic resonance imaging (MRI) for joint swelling.
Disclosures: The study was financially supported by AbbVie. Some of the authors reported receiving research grants, consulting fees, and speaker fees from various sources including AbbVie.
Source: Felbo SK et al. Rheumatology (Oxford). 2021 Apr 24. doi: 10.1093/rheumatology/keab384.
Key clinical point: Joint tenderness showed poor association with imaging signs of inflammation in patients with psoriatic arthritis (PsA).
Major finding: Tender or swollen joint count showed no significant correlations with imaging inflammation sum-scores. Negligible to weak correlation (rho, −0.31 to 0.38) was observed between imaging inflammation sum-scores and the respective clinical joint counts, patient-reported outcomes, and composite scores with no consistently significant results.
Study details: This was a cross-sectional study of 41 patients with active PsA assessed by ultrasound and magnetic resonance imaging (MRI) for joint swelling.
Disclosures: The study was financially supported by AbbVie. Some of the authors reported receiving research grants, consulting fees, and speaker fees from various sources including AbbVie.
Source: Felbo SK et al. Rheumatology (Oxford). 2021 Apr 24. doi: 10.1093/rheumatology/keab384.
Once-weekly oral antipsychotic for schizophrenia on the horizon
A novel, ultra–long-acting oral formulation of the antipsychotic risperidone (Risperdal) only needs to be taken once weekly and appears to be safe and effective, results of a new phase 2 study suggest.
The new formulation, LYN-005 (Lyndra Therapeutics), quickly reached therapeutic levels in patients, provided sustained exposure to risperidone active moiety over 7 days, and reduced peak drug exposure.
“This novel formulation has the potential to improve treatment adherence and quality of life in patients with schizophrenia or schizoaffective disorder,” study investigator David Walling, PhD, chief clinical officer for the Collaborative NeuroScience Network, Long Beach, Calif., said in an interview.
The findings were presented at the 2021 American Society of Clinical Psychopharmacology annual meeting.
Adherence is key
About 50% of patients don’t take medications as prescribed, creating a significant relapse risk, Dr. Walling noted.
“Here we have the possibility of having a once-weekly oral medication, which means patients don’t have to struggle with the issue of taking the medication daily. Right now, all we have on the market for long-acting medications for schizophrenia are injectables, where the patient has to go get a shot every month or every 2 weeks in order to have the medication in their system for a longer period of time,” he added.
The study included 32 clinically stable patients with a primary diagnosis of schizophrenia or schizoaffective disorder.
Patients received immediate-release (IR) risperidone at 2 mg or 4 mg, based on their current antipsychotic dose, for 13 days.
They were then randomly assigned 3:1 to receive either IR risperidone-matched placebo and LYN-005 at 14 mg or 28 mg risperidone (12 patients per group), or to LYN-005 matched placebo and IR risperidone, 2 mg or 4 mg, (4 patients per group) for 3 weeks.
LYN-05 was administered once weekly for a total of three doses. IR risperidone was administered once daily.
The study’s primary endpoints were pharmacokinetics after LYN-005 and IR risperidone and the incidence of adverse events.
Following LYN-005 administration, systemic exposure to risperidone active moiety (risperidone and 9-hydroxyrisperidone combined) increased with the increasing dose. Peak concentration occurred within the first 3 days of dosing and peak exposures from LYN-005 were lower than with IR risperidone.
“Steady state was achieved around day 15. It didn’t take 3 weeks of dosing for patients to achieve steady state. We achieved that around day 15,” Dr. Walling said.
LYN-005 was well tolerated in the 85% of study participants who received all three doses.
Adverse events occurred in 18 (75%) patients who received LYN-005. Of these, 10 were with the 14-mg dose, and 8 with the 28-mg dose.
The most common AEs were gastrointestinal, which occurred in 13 (54%) patients receiving LYN-005, with a higher incidence in the 28-mg group than in the 14 mg group.
Additionally, nine patients had abdominal pain, discomfort, or tenderness, and five patients (21%) had nausea.
Overall, the incidence of adverse events was higher for LYN-005, compared with IR risperidone, but they were judged to be mild and transitory, with fewer AEs reported with subsequent LYN-005 dosing. After the first dose, 58% of patients reported an AE; this dropped to 18% after the third dose.
An important development
Commenting on the findings, Ira D. Glick, MD, professor emeritus, Stanford (Calif.) University, said: “The major problem with schizophrenia is getting adherence.”
“The better the adherence, the better the outcome, the worst the adherence, the worse the outcome, so being able to take a preparation less often is a very important advance in the field,” said Dr. Glick, who was not involved in the research
Long-acting preparations for chronic mental illness represent a significant advance, he said.
“The future of the treatment of schizophrenia is long-acting injectables. That is the trend,” Dr. Glick explained. “The oral once-a-week preparation may be useful in a group of patients who are phobic about needles, but with the injections, you can be sure that the patient has received their medication. With the oral, there is more of a chance to be noncompliant.
“That said, having an effective, longer-acting oral for those who refuse injections is helpful. to ensure adherence to treatment. We know treatment works, we know it is going to save lives, and that’s what this ultra–long-acting formulation is promoting.”
Dr. Glick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel, ultra–long-acting oral formulation of the antipsychotic risperidone (Risperdal) only needs to be taken once weekly and appears to be safe and effective, results of a new phase 2 study suggest.
The new formulation, LYN-005 (Lyndra Therapeutics), quickly reached therapeutic levels in patients, provided sustained exposure to risperidone active moiety over 7 days, and reduced peak drug exposure.
“This novel formulation has the potential to improve treatment adherence and quality of life in patients with schizophrenia or schizoaffective disorder,” study investigator David Walling, PhD, chief clinical officer for the Collaborative NeuroScience Network, Long Beach, Calif., said in an interview.
The findings were presented at the 2021 American Society of Clinical Psychopharmacology annual meeting.
Adherence is key
About 50% of patients don’t take medications as prescribed, creating a significant relapse risk, Dr. Walling noted.
“Here we have the possibility of having a once-weekly oral medication, which means patients don’t have to struggle with the issue of taking the medication daily. Right now, all we have on the market for long-acting medications for schizophrenia are injectables, where the patient has to go get a shot every month or every 2 weeks in order to have the medication in their system for a longer period of time,” he added.
The study included 32 clinically stable patients with a primary diagnosis of schizophrenia or schizoaffective disorder.
Patients received immediate-release (IR) risperidone at 2 mg or 4 mg, based on their current antipsychotic dose, for 13 days.
They were then randomly assigned 3:1 to receive either IR risperidone-matched placebo and LYN-005 at 14 mg or 28 mg risperidone (12 patients per group), or to LYN-005 matched placebo and IR risperidone, 2 mg or 4 mg, (4 patients per group) for 3 weeks.
LYN-05 was administered once weekly for a total of three doses. IR risperidone was administered once daily.
The study’s primary endpoints were pharmacokinetics after LYN-005 and IR risperidone and the incidence of adverse events.
Following LYN-005 administration, systemic exposure to risperidone active moiety (risperidone and 9-hydroxyrisperidone combined) increased with the increasing dose. Peak concentration occurred within the first 3 days of dosing and peak exposures from LYN-005 were lower than with IR risperidone.
“Steady state was achieved around day 15. It didn’t take 3 weeks of dosing for patients to achieve steady state. We achieved that around day 15,” Dr. Walling said.
LYN-005 was well tolerated in the 85% of study participants who received all three doses.
Adverse events occurred in 18 (75%) patients who received LYN-005. Of these, 10 were with the 14-mg dose, and 8 with the 28-mg dose.
The most common AEs were gastrointestinal, which occurred in 13 (54%) patients receiving LYN-005, with a higher incidence in the 28-mg group than in the 14 mg group.
Additionally, nine patients had abdominal pain, discomfort, or tenderness, and five patients (21%) had nausea.
Overall, the incidence of adverse events was higher for LYN-005, compared with IR risperidone, but they were judged to be mild and transitory, with fewer AEs reported with subsequent LYN-005 dosing. After the first dose, 58% of patients reported an AE; this dropped to 18% after the third dose.
An important development
Commenting on the findings, Ira D. Glick, MD, professor emeritus, Stanford (Calif.) University, said: “The major problem with schizophrenia is getting adherence.”
“The better the adherence, the better the outcome, the worst the adherence, the worse the outcome, so being able to take a preparation less often is a very important advance in the field,” said Dr. Glick, who was not involved in the research
Long-acting preparations for chronic mental illness represent a significant advance, he said.
“The future of the treatment of schizophrenia is long-acting injectables. That is the trend,” Dr. Glick explained. “The oral once-a-week preparation may be useful in a group of patients who are phobic about needles, but with the injections, you can be sure that the patient has received their medication. With the oral, there is more of a chance to be noncompliant.
“That said, having an effective, longer-acting oral for those who refuse injections is helpful. to ensure adherence to treatment. We know treatment works, we know it is going to save lives, and that’s what this ultra–long-acting formulation is promoting.”
Dr. Glick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel, ultra–long-acting oral formulation of the antipsychotic risperidone (Risperdal) only needs to be taken once weekly and appears to be safe and effective, results of a new phase 2 study suggest.
The new formulation, LYN-005 (Lyndra Therapeutics), quickly reached therapeutic levels in patients, provided sustained exposure to risperidone active moiety over 7 days, and reduced peak drug exposure.
“This novel formulation has the potential to improve treatment adherence and quality of life in patients with schizophrenia or schizoaffective disorder,” study investigator David Walling, PhD, chief clinical officer for the Collaborative NeuroScience Network, Long Beach, Calif., said in an interview.
The findings were presented at the 2021 American Society of Clinical Psychopharmacology annual meeting.
Adherence is key
About 50% of patients don’t take medications as prescribed, creating a significant relapse risk, Dr. Walling noted.
“Here we have the possibility of having a once-weekly oral medication, which means patients don’t have to struggle with the issue of taking the medication daily. Right now, all we have on the market for long-acting medications for schizophrenia are injectables, where the patient has to go get a shot every month or every 2 weeks in order to have the medication in their system for a longer period of time,” he added.
The study included 32 clinically stable patients with a primary diagnosis of schizophrenia or schizoaffective disorder.
Patients received immediate-release (IR) risperidone at 2 mg or 4 mg, based on their current antipsychotic dose, for 13 days.
They were then randomly assigned 3:1 to receive either IR risperidone-matched placebo and LYN-005 at 14 mg or 28 mg risperidone (12 patients per group), or to LYN-005 matched placebo and IR risperidone, 2 mg or 4 mg, (4 patients per group) for 3 weeks.
LYN-05 was administered once weekly for a total of three doses. IR risperidone was administered once daily.
The study’s primary endpoints were pharmacokinetics after LYN-005 and IR risperidone and the incidence of adverse events.
Following LYN-005 administration, systemic exposure to risperidone active moiety (risperidone and 9-hydroxyrisperidone combined) increased with the increasing dose. Peak concentration occurred within the first 3 days of dosing and peak exposures from LYN-005 were lower than with IR risperidone.
“Steady state was achieved around day 15. It didn’t take 3 weeks of dosing for patients to achieve steady state. We achieved that around day 15,” Dr. Walling said.
LYN-005 was well tolerated in the 85% of study participants who received all three doses.
Adverse events occurred in 18 (75%) patients who received LYN-005. Of these, 10 were with the 14-mg dose, and 8 with the 28-mg dose.
The most common AEs were gastrointestinal, which occurred in 13 (54%) patients receiving LYN-005, with a higher incidence in the 28-mg group than in the 14 mg group.
Additionally, nine patients had abdominal pain, discomfort, or tenderness, and five patients (21%) had nausea.
Overall, the incidence of adverse events was higher for LYN-005, compared with IR risperidone, but they were judged to be mild and transitory, with fewer AEs reported with subsequent LYN-005 dosing. After the first dose, 58% of patients reported an AE; this dropped to 18% after the third dose.
An important development
Commenting on the findings, Ira D. Glick, MD, professor emeritus, Stanford (Calif.) University, said: “The major problem with schizophrenia is getting adherence.”
“The better the adherence, the better the outcome, the worst the adherence, the worse the outcome, so being able to take a preparation less often is a very important advance in the field,” said Dr. Glick, who was not involved in the research
Long-acting preparations for chronic mental illness represent a significant advance, he said.
“The future of the treatment of schizophrenia is long-acting injectables. That is the trend,” Dr. Glick explained. “The oral once-a-week preparation may be useful in a group of patients who are phobic about needles, but with the injections, you can be sure that the patient has received their medication. With the oral, there is more of a chance to be noncompliant.
“That said, having an effective, longer-acting oral for those who refuse injections is helpful. to ensure adherence to treatment. We know treatment works, we know it is going to save lives, and that’s what this ultra–long-acting formulation is promoting.”
Dr. Glick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
PsA tied with higher prevalence of coronary calcification
Key clinical point: In a cohort of at-risk patients with symptoms suggestive of coronary artery disease (CAD), the prevalence of coronary artery calcification (CAC) was higher in patients with psoriatic arthritis (PsA) compared with those without psoriasis or PsA.
Major finding: The prevalence of CAC score greater than 0 was significantly higher in patients with PsA vs. those without psoriasis or PsA (adjusted odds ratio, 1.28; 95% confidence interval, 1.00-1.64).
Study details: This was a cross-sectional study of 46,022 patient’s at-risk patients with symptoms suggestive of CAD from the Danish national computed tomography angiography registry, among which 1,356 had psoriasis, 370 had PsA whereas, 44,296 patients formed the reference nonpsoriasis/PsA cohort.
Disclosures: The study did not report any source of funding. No conflicts of interest were reported.
Source: Tinggaard AB et al. J Intern Med. 2021 May 12. doi: 10.1111/joim.13311.
Key clinical point: In a cohort of at-risk patients with symptoms suggestive of coronary artery disease (CAD), the prevalence of coronary artery calcification (CAC) was higher in patients with psoriatic arthritis (PsA) compared with those without psoriasis or PsA.
Major finding: The prevalence of CAC score greater than 0 was significantly higher in patients with PsA vs. those without psoriasis or PsA (adjusted odds ratio, 1.28; 95% confidence interval, 1.00-1.64).
Study details: This was a cross-sectional study of 46,022 patient’s at-risk patients with symptoms suggestive of CAD from the Danish national computed tomography angiography registry, among which 1,356 had psoriasis, 370 had PsA whereas, 44,296 patients formed the reference nonpsoriasis/PsA cohort.
Disclosures: The study did not report any source of funding. No conflicts of interest were reported.
Source: Tinggaard AB et al. J Intern Med. 2021 May 12. doi: 10.1111/joim.13311.
Key clinical point: In a cohort of at-risk patients with symptoms suggestive of coronary artery disease (CAD), the prevalence of coronary artery calcification (CAC) was higher in patients with psoriatic arthritis (PsA) compared with those without psoriasis or PsA.
Major finding: The prevalence of CAC score greater than 0 was significantly higher in patients with PsA vs. those without psoriasis or PsA (adjusted odds ratio, 1.28; 95% confidence interval, 1.00-1.64).
Study details: This was a cross-sectional study of 46,022 patient’s at-risk patients with symptoms suggestive of CAD from the Danish national computed tomography angiography registry, among which 1,356 had psoriasis, 370 had PsA whereas, 44,296 patients formed the reference nonpsoriasis/PsA cohort.
Disclosures: The study did not report any source of funding. No conflicts of interest were reported.
Source: Tinggaard AB et al. J Intern Med. 2021 May 12. doi: 10.1111/joim.13311.
PsA: Rates of hospitalized serious infections lower with ustekinumab vs. other biologics
Key clinical point: In patients with psoriasis or psoriatic arthritis (PsA), the risk for hospitalized serious infection was lower among those who initiated ustekinumab than other biologics and apremilast.
Major finding: Compared with ustekinumab, the risk for hospitalized serious infection was higher for adalimumab (combined weighted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.34-2.06), apremilast (HR, 1.42; 95% CI, 1.02-1.96), certolizumab (HR, 1.09; 95% CI, 0.68-1.75), etanercept (HR, 1.39; 95% CI, 1.01-1.90), golimumab (HR, 1.74; 95% CI, 1.00-3.03), infliximab (HR, 2.92; 95% CI, 1.80-4.72), ixekizumab (HR, 2.98; 95% CI, 1.20-7.41), and secukinumab (HR, 1.84; 95% CI, 1.24-2.72).
Study details: Findings are from a population-based cohort study of 123,383 patients with psoriasis/PsA who initiated 1 among ustekinumab, adalimumab, apremilast, certolizumab, etanercept, golimumab, ixekizumab, or secukinumab between 2009 and 2018.
Disclosures: This study was sponsored by the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital. SC Kim, RJ Desai, and JF Merola reported receiving research grants from and/or working as consultants/investigators for various sources. The remaining authors declared no conflicts of interest.
Source: Jin Y et al. Arthritis Care Res (Hoboken). 2021 May 10. doi: 10.1002/acr.24630.
Key clinical point: In patients with psoriasis or psoriatic arthritis (PsA), the risk for hospitalized serious infection was lower among those who initiated ustekinumab than other biologics and apremilast.
Major finding: Compared with ustekinumab, the risk for hospitalized serious infection was higher for adalimumab (combined weighted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.34-2.06), apremilast (HR, 1.42; 95% CI, 1.02-1.96), certolizumab (HR, 1.09; 95% CI, 0.68-1.75), etanercept (HR, 1.39; 95% CI, 1.01-1.90), golimumab (HR, 1.74; 95% CI, 1.00-3.03), infliximab (HR, 2.92; 95% CI, 1.80-4.72), ixekizumab (HR, 2.98; 95% CI, 1.20-7.41), and secukinumab (HR, 1.84; 95% CI, 1.24-2.72).
Study details: Findings are from a population-based cohort study of 123,383 patients with psoriasis/PsA who initiated 1 among ustekinumab, adalimumab, apremilast, certolizumab, etanercept, golimumab, ixekizumab, or secukinumab between 2009 and 2018.
Disclosures: This study was sponsored by the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital. SC Kim, RJ Desai, and JF Merola reported receiving research grants from and/or working as consultants/investigators for various sources. The remaining authors declared no conflicts of interest.
Source: Jin Y et al. Arthritis Care Res (Hoboken). 2021 May 10. doi: 10.1002/acr.24630.
Key clinical point: In patients with psoriasis or psoriatic arthritis (PsA), the risk for hospitalized serious infection was lower among those who initiated ustekinumab than other biologics and apremilast.
Major finding: Compared with ustekinumab, the risk for hospitalized serious infection was higher for adalimumab (combined weighted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.34-2.06), apremilast (HR, 1.42; 95% CI, 1.02-1.96), certolizumab (HR, 1.09; 95% CI, 0.68-1.75), etanercept (HR, 1.39; 95% CI, 1.01-1.90), golimumab (HR, 1.74; 95% CI, 1.00-3.03), infliximab (HR, 2.92; 95% CI, 1.80-4.72), ixekizumab (HR, 2.98; 95% CI, 1.20-7.41), and secukinumab (HR, 1.84; 95% CI, 1.24-2.72).
Study details: Findings are from a population-based cohort study of 123,383 patients with psoriasis/PsA who initiated 1 among ustekinumab, adalimumab, apremilast, certolizumab, etanercept, golimumab, ixekizumab, or secukinumab between 2009 and 2018.
Disclosures: This study was sponsored by the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital. SC Kim, RJ Desai, and JF Merola reported receiving research grants from and/or working as consultants/investigators for various sources. The remaining authors declared no conflicts of interest.
Source: Jin Y et al. Arthritis Care Res (Hoboken). 2021 May 10. doi: 10.1002/acr.24630.
PsA: Swapping biologics gives no remarkable advantage over cycling
Key clinical point: In a real-life cohort of patients with psoriatic arthritis (PsA), using drugs with the same (cycling) mode of action (MoA) after the failure of the previous one was not remarkably better than using the drug with a different MoA (swapping) than the previously failed drug.
Major finding: Drug retention rate was not significantly different between the group that underwent swapping vs. cycling (hazard ratio [HR] 0.95; 95% confidence interval [CI], 0.52-1.74), and effectiveness of swapping was not different from that observed in the first-line prescription group (HR, 1.45; 95% CI, 0.83-2.52).
Study details: This was a monocentric medical records review study of 183 patients with PsA treated with biologic disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs. The medical records were grouped into cycling, swapping, or first-line groups.
Disclosures: The authors did not identify any source of funding. The authors declared no conflicts of interest.
Source: Ariani A et al. Medicine (Baltimore). 2021 Apr 23. doi: 10.1097/MD.0000000000025300.
Key clinical point: In a real-life cohort of patients with psoriatic arthritis (PsA), using drugs with the same (cycling) mode of action (MoA) after the failure of the previous one was not remarkably better than using the drug with a different MoA (swapping) than the previously failed drug.
Major finding: Drug retention rate was not significantly different between the group that underwent swapping vs. cycling (hazard ratio [HR] 0.95; 95% confidence interval [CI], 0.52-1.74), and effectiveness of swapping was not different from that observed in the first-line prescription group (HR, 1.45; 95% CI, 0.83-2.52).
Study details: This was a monocentric medical records review study of 183 patients with PsA treated with biologic disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs. The medical records were grouped into cycling, swapping, or first-line groups.
Disclosures: The authors did not identify any source of funding. The authors declared no conflicts of interest.
Source: Ariani A et al. Medicine (Baltimore). 2021 Apr 23. doi: 10.1097/MD.0000000000025300.
Key clinical point: In a real-life cohort of patients with psoriatic arthritis (PsA), using drugs with the same (cycling) mode of action (MoA) after the failure of the previous one was not remarkably better than using the drug with a different MoA (swapping) than the previously failed drug.
Major finding: Drug retention rate was not significantly different between the group that underwent swapping vs. cycling (hazard ratio [HR] 0.95; 95% confidence interval [CI], 0.52-1.74), and effectiveness of swapping was not different from that observed in the first-line prescription group (HR, 1.45; 95% CI, 0.83-2.52).
Study details: This was a monocentric medical records review study of 183 patients with PsA treated with biologic disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs. The medical records were grouped into cycling, swapping, or first-line groups.
Disclosures: The authors did not identify any source of funding. The authors declared no conflicts of interest.
Source: Ariani A et al. Medicine (Baltimore). 2021 Apr 23. doi: 10.1097/MD.0000000000025300.
PsA: Upadacitinib shows consistent efficacy and safety in patients with inadequate response to biologics
Key clinical point: Upadacitinib showed consistent improvement in signs and symptoms of psoriatic arthritis (PsA) with no new significant safety signals in patients with an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).
Major finding: At 56 weeks, the proportion of patients achieving American College of Rheumatology 20/50/70 and Psoriasis Area Severity Index 75/90/100 responses was 59.7%/40.8%/24.2% and 52.3%/40.8%/26.9%, respectively, with upadacitinib 15 mg and 59.2%/38.5%/26.6% and 58.8%/47.3%/35.1%, respectively, with upadacitinib 30 mg. Improvement was consistent through the study period with both upadacitinib doses with a safety profile consistent with that known previously.
Study details: Findings are from phase 3 SELECT-PsA 2 study, involving 641 patients with PsA who had an inadequate response to at least 1 bDMARD and were randomly allocated to receive upadacitinib 15 mg, 30 mg once daily (OD), or placebo switched to upadacitinib 15 mg or 30 mg OD at week 24.
Disclosures: SELECT-PsA 2 trial was funded by AbbVie. The authors reported receiving grants/consulting fees, speaker fees from, being employees of, and stockholder from various sources including AbbVie.
Source: Mease PJ et al. Rheumatol Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z.
Key clinical point: Upadacitinib showed consistent improvement in signs and symptoms of psoriatic arthritis (PsA) with no new significant safety signals in patients with an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).
Major finding: At 56 weeks, the proportion of patients achieving American College of Rheumatology 20/50/70 and Psoriasis Area Severity Index 75/90/100 responses was 59.7%/40.8%/24.2% and 52.3%/40.8%/26.9%, respectively, with upadacitinib 15 mg and 59.2%/38.5%/26.6% and 58.8%/47.3%/35.1%, respectively, with upadacitinib 30 mg. Improvement was consistent through the study period with both upadacitinib doses with a safety profile consistent with that known previously.
Study details: Findings are from phase 3 SELECT-PsA 2 study, involving 641 patients with PsA who had an inadequate response to at least 1 bDMARD and were randomly allocated to receive upadacitinib 15 mg, 30 mg once daily (OD), or placebo switched to upadacitinib 15 mg or 30 mg OD at week 24.
Disclosures: SELECT-PsA 2 trial was funded by AbbVie. The authors reported receiving grants/consulting fees, speaker fees from, being employees of, and stockholder from various sources including AbbVie.
Source: Mease PJ et al. Rheumatol Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z.
Key clinical point: Upadacitinib showed consistent improvement in signs and symptoms of psoriatic arthritis (PsA) with no new significant safety signals in patients with an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).
Major finding: At 56 weeks, the proportion of patients achieving American College of Rheumatology 20/50/70 and Psoriasis Area Severity Index 75/90/100 responses was 59.7%/40.8%/24.2% and 52.3%/40.8%/26.9%, respectively, with upadacitinib 15 mg and 59.2%/38.5%/26.6% and 58.8%/47.3%/35.1%, respectively, with upadacitinib 30 mg. Improvement was consistent through the study period with both upadacitinib doses with a safety profile consistent with that known previously.
Study details: Findings are from phase 3 SELECT-PsA 2 study, involving 641 patients with PsA who had an inadequate response to at least 1 bDMARD and were randomly allocated to receive upadacitinib 15 mg, 30 mg once daily (OD), or placebo switched to upadacitinib 15 mg or 30 mg OD at week 24.
Disclosures: SELECT-PsA 2 trial was funded by AbbVie. The authors reported receiving grants/consulting fees, speaker fees from, being employees of, and stockholder from various sources including AbbVie.
Source: Mease PJ et al. Rheumatol Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z.