Stroke policy recommendations incorporate advances in endovascular therapy

Transport algorithms must account for uncertainty
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Stroke centers need to collaborate within their regions to assure best practices and optimal access to comprehensive stroke centers as well as newly-designated thrombectomy-capable stroke centers, according to an updated policy statement from the American Stroke Association published in Stroke.

Dr. Opeolu Adeoye

Opeolu Adeoye, MD, associate professor of emergency medicine and neurosurgery at the University of Cincinnati – and chair of the policy statement writing group – and coauthors updated the ASA’s 2005 recommendations for policy makers and public health care agencies to reflect current evidence, the increased availability of endovascular therapy, and new stroke center certifications.

“We have seen monumental advancements in acute stroke care over the past 14 years, and our concept of a comprehensive stroke system of care has evolved as a result,” Dr. Adeoye said in a news release.

While a recommendation to support the initiation of stroke prevention regimens remains unchanged from the 2005 recommendations, the 2019 update emphasizes a need to support long-term adherence to such regimens. To that end, researchers should examine the potential benefits of stroke prevention efforts that incorporate social media, gamification, and other technologies and principles to promote healthy behavior, the authors suggested. Furthermore, technology may allow for the passive surveillance of baseline behaviors and enable researchers to track changes in behavior over time.

Thrombectomy-capable centers

Thrombectomy-capable stroke centers, which have capabilities between those of primary stroke centers and comprehensive stroke centers, provide a relatively new level of acute stroke care. In communities that do not otherwise have access to thrombectomy, these centers play a clear role. In communities with comprehensive stroke centers, their role “is more controversial, and routing plans for patients with a suspected LVO [large vessel occlusion] should always seek the center of highest capability when travel time differences are short,” the statement says.

Timely parenchymal and arterial imaging via CT or MRI are needed to identify the subset of patients who may benefit from thrombectomy. All centers managing stroke patients should develop a plan for the definitive identification and treatment of these patients. Imaging techniques that assess penumbral patterns to identify candidates for endovascular therapy between 6 and 24 hours after patients were last known to be normal “merit broader adoption,” the statement says.

Hospitals without thrombectomy capability should have transfer protocols to allow the rapid treatment of these patients to hospitals with the appropriate level of care. In rural facilities that lack 24/7 imaging and radiology capabilities, this may mean rapid transfer of patients with clinically suspected LVO to hospitals where their work-up may be expedited.

To improve process, centers providing thrombectomy should rigorously track patient flow at all time points from presentation to imaging to intervention. Reperfusion rates, procedural complications, and patient clinical outcomes must be tracked and reported.

Travel times

Triage paradigms and protocols should be developed to ensure that emergency medical service (EMS) providers are able to rapidly identify all patients with a known or suspected stroke and to assess them with a validated and standardized instrument for stroke screening such as FAST (Face, Arm, Speech, Time), Los Angeles Prehospital Stroke Screen, or Cincinnati Prehospital Stroke Scale.

In prehospital patients who screen positive for suspected stroke, a standard prehospital stroke severity assessment tool such as the Cincinnati Stroke Triage Assessment Tool, Rapid Arterial Occlusion Evaluation, Los Angeles Motor Scale, or Field Assessment Stroke Triage for Emergency Destination should be used. “Further research is needed to establish the most effective prehospital stroke severity triage scale,” the authors noted. In all cases, EMS should notify hospitals that a stroke patient is en route.

“When there are several intravenous alteplase–capable hospitals in a well-defined geographic region, extra transportation times to reach a facility capable of endovascular thrombectomy should be limited to no more than 15 minutes in patients with a prehospital stroke severity score suggestive of LVO,” according to the recommendations. “When several hospital options exist within similar travel times, EMS should seek care at the facility capable of offering the highest level of stroke care. Further research is needed to establish travel time parameters for hospital bypass in cases of prehospital suspicion of LVO.”

Outcomes and discharge

Centers should track various treatment and patient outcomes, and all patients discharged to their homes should have appropriate follow-up with specialized stroke services and primary care and be screened for postacute complications.

Government institutions should standardize the organization of stroke care, ensure that stroke patients receive timely care at appropriate hospitals, and facilitate access to secondary prevention and rehabilitation resources after stroke, the authors wrote.

“Programs geared at further improving the knowledge of the public, encouraging primordial and primary prevention, advancing and facilitating acute therapy, improving secondary prevention and recovery from stroke, and reducing disparities in stroke care should be actively developed in a coordinated and collaborative fashion by providers and policymakers at the local, state, and national levels,” the authors concluded. “Such efforts will continue to mitigate the effects of stroke on society.”

Dr. Adeoye had no disclosures. Some coauthors reported research grants and consultant or advisory board positions.

SOURCE: Adeoye O et al. Stroke. 2019 May 20. doi: 10.1161/STR.0000000000000173.

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When determining where to transport a patient with stroke, uncertainty about the patient’s diagnosis and eligibility for thrombectomy is a necessary consideration, said Robert A. Harrington, MD, of Stanford University (Calif.), in an accompanying editorial.

In lieu of better data, stroke systems should follow the recommendation of the Mission: Lifeline Severity-based Stroke Triage Algorithm for emergency medical services to avoid more than 15 minutes of additional travel time to transport a patient to a center that can perform endovascular therapy when the patient may be eligible for intravenous tissue plasminogen activator (tPA), said Dr. Harrington.

Delays in initiating tPA could lead to some patients not receiving treatment. “Some patients with suspected LVO [large vessel occlusion] either will not have thrombectomy or will not be eligible for it, and they also run the risk of not receiving any acute reperfusion therapy. Consequently, transport algorithms and models must take into account the uncertainty in prehospital diagnosis when considering the most appropriate facility,” he said.

Forthcoming acute stroke guidelines “will recommend intravenous tPA for all eligible subjects” because administration of tPA before endovascular thrombectomy does not appear to be harmful, Dr. Harrington noted.

Ultimately, approaches to routing patients may vary by region. “It is up to local and regional communities ... to define how best to implement these elements into a stroke system of care that meets their needs and resources and to define the types of hospitals that should qualify as points of entry for patients with suspected LVO strokes,” Dr. Harrington said.

A group convened by the American Heart Association and American Stroke Association is drafting further guiding principles for stroke systems of care in various regional settings.

Dr. Harrington is president-elect of the American Heart Association. He reported receiving research grants from AstraZeneca and Bristol-Myers Squibb.

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When determining where to transport a patient with stroke, uncertainty about the patient’s diagnosis and eligibility for thrombectomy is a necessary consideration, said Robert A. Harrington, MD, of Stanford University (Calif.), in an accompanying editorial.

In lieu of better data, stroke systems should follow the recommendation of the Mission: Lifeline Severity-based Stroke Triage Algorithm for emergency medical services to avoid more than 15 minutes of additional travel time to transport a patient to a center that can perform endovascular therapy when the patient may be eligible for intravenous tissue plasminogen activator (tPA), said Dr. Harrington.

Delays in initiating tPA could lead to some patients not receiving treatment. “Some patients with suspected LVO [large vessel occlusion] either will not have thrombectomy or will not be eligible for it, and they also run the risk of not receiving any acute reperfusion therapy. Consequently, transport algorithms and models must take into account the uncertainty in prehospital diagnosis when considering the most appropriate facility,” he said.

Forthcoming acute stroke guidelines “will recommend intravenous tPA for all eligible subjects” because administration of tPA before endovascular thrombectomy does not appear to be harmful, Dr. Harrington noted.

Ultimately, approaches to routing patients may vary by region. “It is up to local and regional communities ... to define how best to implement these elements into a stroke system of care that meets their needs and resources and to define the types of hospitals that should qualify as points of entry for patients with suspected LVO strokes,” Dr. Harrington said.

A group convened by the American Heart Association and American Stroke Association is drafting further guiding principles for stroke systems of care in various regional settings.

Dr. Harrington is president-elect of the American Heart Association. He reported receiving research grants from AstraZeneca and Bristol-Myers Squibb.

Body

 

When determining where to transport a patient with stroke, uncertainty about the patient’s diagnosis and eligibility for thrombectomy is a necessary consideration, said Robert A. Harrington, MD, of Stanford University (Calif.), in an accompanying editorial.

In lieu of better data, stroke systems should follow the recommendation of the Mission: Lifeline Severity-based Stroke Triage Algorithm for emergency medical services to avoid more than 15 minutes of additional travel time to transport a patient to a center that can perform endovascular therapy when the patient may be eligible for intravenous tissue plasminogen activator (tPA), said Dr. Harrington.

Delays in initiating tPA could lead to some patients not receiving treatment. “Some patients with suspected LVO [large vessel occlusion] either will not have thrombectomy or will not be eligible for it, and they also run the risk of not receiving any acute reperfusion therapy. Consequently, transport algorithms and models must take into account the uncertainty in prehospital diagnosis when considering the most appropriate facility,” he said.

Forthcoming acute stroke guidelines “will recommend intravenous tPA for all eligible subjects” because administration of tPA before endovascular thrombectomy does not appear to be harmful, Dr. Harrington noted.

Ultimately, approaches to routing patients may vary by region. “It is up to local and regional communities ... to define how best to implement these elements into a stroke system of care that meets their needs and resources and to define the types of hospitals that should qualify as points of entry for patients with suspected LVO strokes,” Dr. Harrington said.

A group convened by the American Heart Association and American Stroke Association is drafting further guiding principles for stroke systems of care in various regional settings.

Dr. Harrington is president-elect of the American Heart Association. He reported receiving research grants from AstraZeneca and Bristol-Myers Squibb.

Title
Transport algorithms must account for uncertainty
Transport algorithms must account for uncertainty

 

Stroke centers need to collaborate within their regions to assure best practices and optimal access to comprehensive stroke centers as well as newly-designated thrombectomy-capable stroke centers, according to an updated policy statement from the American Stroke Association published in Stroke.

Dr. Opeolu Adeoye

Opeolu Adeoye, MD, associate professor of emergency medicine and neurosurgery at the University of Cincinnati – and chair of the policy statement writing group – and coauthors updated the ASA’s 2005 recommendations for policy makers and public health care agencies to reflect current evidence, the increased availability of endovascular therapy, and new stroke center certifications.

“We have seen monumental advancements in acute stroke care over the past 14 years, and our concept of a comprehensive stroke system of care has evolved as a result,” Dr. Adeoye said in a news release.

While a recommendation to support the initiation of stroke prevention regimens remains unchanged from the 2005 recommendations, the 2019 update emphasizes a need to support long-term adherence to such regimens. To that end, researchers should examine the potential benefits of stroke prevention efforts that incorporate social media, gamification, and other technologies and principles to promote healthy behavior, the authors suggested. Furthermore, technology may allow for the passive surveillance of baseline behaviors and enable researchers to track changes in behavior over time.

Thrombectomy-capable centers

Thrombectomy-capable stroke centers, which have capabilities between those of primary stroke centers and comprehensive stroke centers, provide a relatively new level of acute stroke care. In communities that do not otherwise have access to thrombectomy, these centers play a clear role. In communities with comprehensive stroke centers, their role “is more controversial, and routing plans for patients with a suspected LVO [large vessel occlusion] should always seek the center of highest capability when travel time differences are short,” the statement says.

Timely parenchymal and arterial imaging via CT or MRI are needed to identify the subset of patients who may benefit from thrombectomy. All centers managing stroke patients should develop a plan for the definitive identification and treatment of these patients. Imaging techniques that assess penumbral patterns to identify candidates for endovascular therapy between 6 and 24 hours after patients were last known to be normal “merit broader adoption,” the statement says.

Hospitals without thrombectomy capability should have transfer protocols to allow the rapid treatment of these patients to hospitals with the appropriate level of care. In rural facilities that lack 24/7 imaging and radiology capabilities, this may mean rapid transfer of patients with clinically suspected LVO to hospitals where their work-up may be expedited.

To improve process, centers providing thrombectomy should rigorously track patient flow at all time points from presentation to imaging to intervention. Reperfusion rates, procedural complications, and patient clinical outcomes must be tracked and reported.

Travel times

Triage paradigms and protocols should be developed to ensure that emergency medical service (EMS) providers are able to rapidly identify all patients with a known or suspected stroke and to assess them with a validated and standardized instrument for stroke screening such as FAST (Face, Arm, Speech, Time), Los Angeles Prehospital Stroke Screen, or Cincinnati Prehospital Stroke Scale.

In prehospital patients who screen positive for suspected stroke, a standard prehospital stroke severity assessment tool such as the Cincinnati Stroke Triage Assessment Tool, Rapid Arterial Occlusion Evaluation, Los Angeles Motor Scale, or Field Assessment Stroke Triage for Emergency Destination should be used. “Further research is needed to establish the most effective prehospital stroke severity triage scale,” the authors noted. In all cases, EMS should notify hospitals that a stroke patient is en route.

“When there are several intravenous alteplase–capable hospitals in a well-defined geographic region, extra transportation times to reach a facility capable of endovascular thrombectomy should be limited to no more than 15 minutes in patients with a prehospital stroke severity score suggestive of LVO,” according to the recommendations. “When several hospital options exist within similar travel times, EMS should seek care at the facility capable of offering the highest level of stroke care. Further research is needed to establish travel time parameters for hospital bypass in cases of prehospital suspicion of LVO.”

Outcomes and discharge

Centers should track various treatment and patient outcomes, and all patients discharged to their homes should have appropriate follow-up with specialized stroke services and primary care and be screened for postacute complications.

Government institutions should standardize the organization of stroke care, ensure that stroke patients receive timely care at appropriate hospitals, and facilitate access to secondary prevention and rehabilitation resources after stroke, the authors wrote.

“Programs geared at further improving the knowledge of the public, encouraging primordial and primary prevention, advancing and facilitating acute therapy, improving secondary prevention and recovery from stroke, and reducing disparities in stroke care should be actively developed in a coordinated and collaborative fashion by providers and policymakers at the local, state, and national levels,” the authors concluded. “Such efforts will continue to mitigate the effects of stroke on society.”

Dr. Adeoye had no disclosures. Some coauthors reported research grants and consultant or advisory board positions.

SOURCE: Adeoye O et al. Stroke. 2019 May 20. doi: 10.1161/STR.0000000000000173.

 

Stroke centers need to collaborate within their regions to assure best practices and optimal access to comprehensive stroke centers as well as newly-designated thrombectomy-capable stroke centers, according to an updated policy statement from the American Stroke Association published in Stroke.

Dr. Opeolu Adeoye

Opeolu Adeoye, MD, associate professor of emergency medicine and neurosurgery at the University of Cincinnati – and chair of the policy statement writing group – and coauthors updated the ASA’s 2005 recommendations for policy makers and public health care agencies to reflect current evidence, the increased availability of endovascular therapy, and new stroke center certifications.

“We have seen monumental advancements in acute stroke care over the past 14 years, and our concept of a comprehensive stroke system of care has evolved as a result,” Dr. Adeoye said in a news release.

While a recommendation to support the initiation of stroke prevention regimens remains unchanged from the 2005 recommendations, the 2019 update emphasizes a need to support long-term adherence to such regimens. To that end, researchers should examine the potential benefits of stroke prevention efforts that incorporate social media, gamification, and other technologies and principles to promote healthy behavior, the authors suggested. Furthermore, technology may allow for the passive surveillance of baseline behaviors and enable researchers to track changes in behavior over time.

Thrombectomy-capable centers

Thrombectomy-capable stroke centers, which have capabilities between those of primary stroke centers and comprehensive stroke centers, provide a relatively new level of acute stroke care. In communities that do not otherwise have access to thrombectomy, these centers play a clear role. In communities with comprehensive stroke centers, their role “is more controversial, and routing plans for patients with a suspected LVO [large vessel occlusion] should always seek the center of highest capability when travel time differences are short,” the statement says.

Timely parenchymal and arterial imaging via CT or MRI are needed to identify the subset of patients who may benefit from thrombectomy. All centers managing stroke patients should develop a plan for the definitive identification and treatment of these patients. Imaging techniques that assess penumbral patterns to identify candidates for endovascular therapy between 6 and 24 hours after patients were last known to be normal “merit broader adoption,” the statement says.

Hospitals without thrombectomy capability should have transfer protocols to allow the rapid treatment of these patients to hospitals with the appropriate level of care. In rural facilities that lack 24/7 imaging and radiology capabilities, this may mean rapid transfer of patients with clinically suspected LVO to hospitals where their work-up may be expedited.

To improve process, centers providing thrombectomy should rigorously track patient flow at all time points from presentation to imaging to intervention. Reperfusion rates, procedural complications, and patient clinical outcomes must be tracked and reported.

Travel times

Triage paradigms and protocols should be developed to ensure that emergency medical service (EMS) providers are able to rapidly identify all patients with a known or suspected stroke and to assess them with a validated and standardized instrument for stroke screening such as FAST (Face, Arm, Speech, Time), Los Angeles Prehospital Stroke Screen, or Cincinnati Prehospital Stroke Scale.

In prehospital patients who screen positive for suspected stroke, a standard prehospital stroke severity assessment tool such as the Cincinnati Stroke Triage Assessment Tool, Rapid Arterial Occlusion Evaluation, Los Angeles Motor Scale, or Field Assessment Stroke Triage for Emergency Destination should be used. “Further research is needed to establish the most effective prehospital stroke severity triage scale,” the authors noted. In all cases, EMS should notify hospitals that a stroke patient is en route.

“When there are several intravenous alteplase–capable hospitals in a well-defined geographic region, extra transportation times to reach a facility capable of endovascular thrombectomy should be limited to no more than 15 minutes in patients with a prehospital stroke severity score suggestive of LVO,” according to the recommendations. “When several hospital options exist within similar travel times, EMS should seek care at the facility capable of offering the highest level of stroke care. Further research is needed to establish travel time parameters for hospital bypass in cases of prehospital suspicion of LVO.”

Outcomes and discharge

Centers should track various treatment and patient outcomes, and all patients discharged to their homes should have appropriate follow-up with specialized stroke services and primary care and be screened for postacute complications.

Government institutions should standardize the organization of stroke care, ensure that stroke patients receive timely care at appropriate hospitals, and facilitate access to secondary prevention and rehabilitation resources after stroke, the authors wrote.

“Programs geared at further improving the knowledge of the public, encouraging primordial and primary prevention, advancing and facilitating acute therapy, improving secondary prevention and recovery from stroke, and reducing disparities in stroke care should be actively developed in a coordinated and collaborative fashion by providers and policymakers at the local, state, and national levels,” the authors concluded. “Such efforts will continue to mitigate the effects of stroke on society.”

Dr. Adeoye had no disclosures. Some coauthors reported research grants and consultant or advisory board positions.

SOURCE: Adeoye O et al. Stroke. 2019 May 20. doi: 10.1161/STR.0000000000000173.

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Life After Liver Transplantation

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New study explores the “practical aspects of life after liver transplantation,” and looks into the health care resources available for patients after discharge.

Liver transplantation (LT) is “one of the most resource-intense procedures despite significant improvements in procedures and protocols,” say researchers from Seoul National University Hospital in South Korea. But little is known about the “practical aspects of life after liver transplantation,” such as unplanned visits to the emergency department (ED) or readmission for complications. So the researchers conducted a study to find out what health care resources are used after discharge.

Of 430 patients, half visited the ED at least once, and 57% were readmitted at least once. The rate of ED visits rose from 15% at 30 days after discharge to 44% at 1 year. Readmission rates more than tripled, from 16% at 30 days to 49% at 1 year.

Contrary to other research, living donor liver transplantation was not a risk factor of readmission. Emergency LT was a risk factor for ED visits and readmission within 30 days of discharge. And although LT using the left liver lobe and pre-existing hepatitis C are known risk factors for long-term graft failure, at the researchers’ hospital hepatitis B is the most common indication for living donor LT. Most of their patients undergo LT using the right liver lobe.

Some of the identified risk factors were unexpected, the researchers say. One was donor age of < 60 years. Warm ischemic time of 15 minutes or longer was another. The researchers note that prolonged warm ischemic time increases hepatic ischemia and reperfusion injury and is related to postoperative complications, which can be a cause of frequent readmission.

Length of stay (LOS)  > 2 weeks also was a risk factor for readmission. In their institution, the average LOS for patients with a warm ischemic time of < 15 minutes was 15.6 days, shorter than the overall average LOS. Shorter LOS, the researchers add, may reflect fewer immediate postoperative complications.

Although they identified no specific complication as a risk factor for readmission, the researchers found specific conditions that accounted for a relatively high proportion of readmissions and repeated readmission, including abnormal liver function test  (32% of readmissions) and fever (17% of readmissions and 39% of repeated readmissions). The researchers suggest those are conditions to monitor and manage.

Notably, patients who did not require readmission or ED visits in the first 20 months almost never required unplanned health care resources thereafter.

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New study explores the “practical aspects of life after liver transplantation,” and looks into the health care resources available for patients after discharge.
New study explores the “practical aspects of life after liver transplantation,” and looks into the health care resources available for patients after discharge.

Liver transplantation (LT) is “one of the most resource-intense procedures despite significant improvements in procedures and protocols,” say researchers from Seoul National University Hospital in South Korea. But little is known about the “practical aspects of life after liver transplantation,” such as unplanned visits to the emergency department (ED) or readmission for complications. So the researchers conducted a study to find out what health care resources are used after discharge.

Of 430 patients, half visited the ED at least once, and 57% were readmitted at least once. The rate of ED visits rose from 15% at 30 days after discharge to 44% at 1 year. Readmission rates more than tripled, from 16% at 30 days to 49% at 1 year.

Contrary to other research, living donor liver transplantation was not a risk factor of readmission. Emergency LT was a risk factor for ED visits and readmission within 30 days of discharge. And although LT using the left liver lobe and pre-existing hepatitis C are known risk factors for long-term graft failure, at the researchers’ hospital hepatitis B is the most common indication for living donor LT. Most of their patients undergo LT using the right liver lobe.

Some of the identified risk factors were unexpected, the researchers say. One was donor age of < 60 years. Warm ischemic time of 15 minutes or longer was another. The researchers note that prolonged warm ischemic time increases hepatic ischemia and reperfusion injury and is related to postoperative complications, which can be a cause of frequent readmission.

Length of stay (LOS)  > 2 weeks also was a risk factor for readmission. In their institution, the average LOS for patients with a warm ischemic time of < 15 minutes was 15.6 days, shorter than the overall average LOS. Shorter LOS, the researchers add, may reflect fewer immediate postoperative complications.

Although they identified no specific complication as a risk factor for readmission, the researchers found specific conditions that accounted for a relatively high proportion of readmissions and repeated readmission, including abnormal liver function test  (32% of readmissions) and fever (17% of readmissions and 39% of repeated readmissions). The researchers suggest those are conditions to monitor and manage.

Notably, patients who did not require readmission or ED visits in the first 20 months almost never required unplanned health care resources thereafter.

Liver transplantation (LT) is “one of the most resource-intense procedures despite significant improvements in procedures and protocols,” say researchers from Seoul National University Hospital in South Korea. But little is known about the “practical aspects of life after liver transplantation,” such as unplanned visits to the emergency department (ED) or readmission for complications. So the researchers conducted a study to find out what health care resources are used after discharge.

Of 430 patients, half visited the ED at least once, and 57% were readmitted at least once. The rate of ED visits rose from 15% at 30 days after discharge to 44% at 1 year. Readmission rates more than tripled, from 16% at 30 days to 49% at 1 year.

Contrary to other research, living donor liver transplantation was not a risk factor of readmission. Emergency LT was a risk factor for ED visits and readmission within 30 days of discharge. And although LT using the left liver lobe and pre-existing hepatitis C are known risk factors for long-term graft failure, at the researchers’ hospital hepatitis B is the most common indication for living donor LT. Most of their patients undergo LT using the right liver lobe.

Some of the identified risk factors were unexpected, the researchers say. One was donor age of < 60 years. Warm ischemic time of 15 minutes or longer was another. The researchers note that prolonged warm ischemic time increases hepatic ischemia and reperfusion injury and is related to postoperative complications, which can be a cause of frequent readmission.

Length of stay (LOS)  > 2 weeks also was a risk factor for readmission. In their institution, the average LOS for patients with a warm ischemic time of < 15 minutes was 15.6 days, shorter than the overall average LOS. Shorter LOS, the researchers add, may reflect fewer immediate postoperative complications.

Although they identified no specific complication as a risk factor for readmission, the researchers found specific conditions that accounted for a relatively high proportion of readmissions and repeated readmission, including abnormal liver function test  (32% of readmissions) and fever (17% of readmissions and 39% of repeated readmissions). The researchers suggest those are conditions to monitor and manage.

Notably, patients who did not require readmission or ED visits in the first 20 months almost never required unplanned health care resources thereafter.

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Early dexmedetomidine did not reduce 90-day mortality in ICU patients on mechanical ventilation

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Dexmedetomidine fell short for reducing 90-day mortality as the primary sedative for patients on mechanical ventilation, according to results of the randomized, controlled, open-label SPICE III trial, which was presented at the annual meeting of the American Thoracic Society and simultaneously published in the New England Journal of Medicine.

“Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation,” Yahya Shehabi, PhD, of Monash University in Clayton, Australia, and colleagues wrote.

The study was conducted in 74 ICUs in eight countries. Researchers randomly assigned 4,000 patients who were critically ill, had received ventilation for less than 12 hours, and were likely to require mechanical ventilation for at least the next day to either dexmedetomidine or usual care (propofol, midazolam, or another sedative). The sedation goal was a Richmond Agitation and Sedation Scale (RASS) score of –2 (lightly sedated) to +1 (restless), and was assessed every 4 hours. Intravenous dexmedetomidine was administered at 1 mcg/kg of body weight per hour without a loading dose and adjusted to a maximum dose of 1.5 mcg/kg per hour to achieve a RASS score in the target range. Use was continued as clinically required for up to 28 days.

The modified intention-to-treat analysis included 3,904 patients. The 90-day mortality rate was 29.1% (556 of 1,948 patients) for patients who received dexmedetomidine and 29.1% (569 of 1,956 patients) for those who received usual care. There was no significant difference for patients with suspected or proven sepsis at randomization and those without sepsis. Mortality did not vary based on country, cause of death, or discharge destination.

Dr. Shehabi and colleagues noted that, for 2 days after randomization, patients who received dexmedetomidine were also given propofol (64% of patients), midazolam (3%), or both (7%) as supplemental sedation. In the control group, 60% of the patients received propofol, 12% received midazolam, and 20% received both. About 80% of patients in both groups received fentanyl. The use of multiple agents may reflect sedation requirements during the acute phase of critical illness.

With regard to adverse events, the patients receiving dexmedetomidine more commonly experienced bradycardia and hypotension than the usual-care group.

SPICE III was funded in part by a grant from the National Health and Medical Research Council of Australia and the National Heart Institute of Malaysia. Dr. Shehabi reports grants from the National Health and Medical Research Council of Australia, nonfinancial and other support from Pfizer, and nonfinancial and other support from Orion Pharma.

SOURCE: Shehabi Y et al. N Eng J Med. 2019 May 19. doi: 10.1056/NEJMoa1904710.

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Dexmedetomidine fell short for reducing 90-day mortality as the primary sedative for patients on mechanical ventilation, according to results of the randomized, controlled, open-label SPICE III trial, which was presented at the annual meeting of the American Thoracic Society and simultaneously published in the New England Journal of Medicine.

“Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation,” Yahya Shehabi, PhD, of Monash University in Clayton, Australia, and colleagues wrote.

The study was conducted in 74 ICUs in eight countries. Researchers randomly assigned 4,000 patients who were critically ill, had received ventilation for less than 12 hours, and were likely to require mechanical ventilation for at least the next day to either dexmedetomidine or usual care (propofol, midazolam, or another sedative). The sedation goal was a Richmond Agitation and Sedation Scale (RASS) score of –2 (lightly sedated) to +1 (restless), and was assessed every 4 hours. Intravenous dexmedetomidine was administered at 1 mcg/kg of body weight per hour without a loading dose and adjusted to a maximum dose of 1.5 mcg/kg per hour to achieve a RASS score in the target range. Use was continued as clinically required for up to 28 days.

The modified intention-to-treat analysis included 3,904 patients. The 90-day mortality rate was 29.1% (556 of 1,948 patients) for patients who received dexmedetomidine and 29.1% (569 of 1,956 patients) for those who received usual care. There was no significant difference for patients with suspected or proven sepsis at randomization and those without sepsis. Mortality did not vary based on country, cause of death, or discharge destination.

Dr. Shehabi and colleagues noted that, for 2 days after randomization, patients who received dexmedetomidine were also given propofol (64% of patients), midazolam (3%), or both (7%) as supplemental sedation. In the control group, 60% of the patients received propofol, 12% received midazolam, and 20% received both. About 80% of patients in both groups received fentanyl. The use of multiple agents may reflect sedation requirements during the acute phase of critical illness.

With regard to adverse events, the patients receiving dexmedetomidine more commonly experienced bradycardia and hypotension than the usual-care group.

SPICE III was funded in part by a grant from the National Health and Medical Research Council of Australia and the National Heart Institute of Malaysia. Dr. Shehabi reports grants from the National Health and Medical Research Council of Australia, nonfinancial and other support from Pfizer, and nonfinancial and other support from Orion Pharma.

SOURCE: Shehabi Y et al. N Eng J Med. 2019 May 19. doi: 10.1056/NEJMoa1904710.

 

Dexmedetomidine fell short for reducing 90-day mortality as the primary sedative for patients on mechanical ventilation, according to results of the randomized, controlled, open-label SPICE III trial, which was presented at the annual meeting of the American Thoracic Society and simultaneously published in the New England Journal of Medicine.

“Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation,” Yahya Shehabi, PhD, of Monash University in Clayton, Australia, and colleagues wrote.

The study was conducted in 74 ICUs in eight countries. Researchers randomly assigned 4,000 patients who were critically ill, had received ventilation for less than 12 hours, and were likely to require mechanical ventilation for at least the next day to either dexmedetomidine or usual care (propofol, midazolam, or another sedative). The sedation goal was a Richmond Agitation and Sedation Scale (RASS) score of –2 (lightly sedated) to +1 (restless), and was assessed every 4 hours. Intravenous dexmedetomidine was administered at 1 mcg/kg of body weight per hour without a loading dose and adjusted to a maximum dose of 1.5 mcg/kg per hour to achieve a RASS score in the target range. Use was continued as clinically required for up to 28 days.

The modified intention-to-treat analysis included 3,904 patients. The 90-day mortality rate was 29.1% (556 of 1,948 patients) for patients who received dexmedetomidine and 29.1% (569 of 1,956 patients) for those who received usual care. There was no significant difference for patients with suspected or proven sepsis at randomization and those without sepsis. Mortality did not vary based on country, cause of death, or discharge destination.

Dr. Shehabi and colleagues noted that, for 2 days after randomization, patients who received dexmedetomidine were also given propofol (64% of patients), midazolam (3%), or both (7%) as supplemental sedation. In the control group, 60% of the patients received propofol, 12% received midazolam, and 20% received both. About 80% of patients in both groups received fentanyl. The use of multiple agents may reflect sedation requirements during the acute phase of critical illness.

With regard to adverse events, the patients receiving dexmedetomidine more commonly experienced bradycardia and hypotension than the usual-care group.

SPICE III was funded in part by a grant from the National Health and Medical Research Council of Australia and the National Heart Institute of Malaysia. Dr. Shehabi reports grants from the National Health and Medical Research Council of Australia, nonfinancial and other support from Pfizer, and nonfinancial and other support from Orion Pharma.

SOURCE: Shehabi Y et al. N Eng J Med. 2019 May 19. doi: 10.1056/NEJMoa1904710.

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Key clinical point: Patients receiving dexmedetomidine for sedation had a comparable 90-day mortality rate with patients who received usual care.

Major finding: The mortality rate at 90 days was 29.1% (556 of 1,948 patients) for patients who received dexmedetomidine and 29.1% (569 of 1,956 patients) for those who received usual care.

Study details: The study was conducted in 74 ICUs in 8 countries. Researchers randomly assigned 4,000 patients who were critically ill, had received ventilation for less than 12 hours, and were likely to require mechanical ventilation for at least the next day to either dexmedetomidine or usual care (propofol, midazolam, or another sedative).

Disclosures: The study was funded in part by a grant from the National Health and Medical Research Council of Australia and the National Heart Institute of Malaysia. Dr. Shehabi reports grants from The National Health and Medical Research Council of Australia, nonfinancial and other support from Pfizer, and nonfinancial and other support from Orion Pharma.Source: Shehabi Y et al. N Eng J Med. 2019 May 19. doi: 10.1056/NEJMoa1904710.

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Toolkit for providing mental health care to Muslim patients launched

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– A toolkit that seeks to help clinicians provide culturally and religiously informed mental health care for Muslim patients was officially launched at the annual meeting of the American Psychiatric Association.

Rania Awaad, MD, and Belinda S. Bandstra, MD, sat down at the annual meeting of the American Psychiatric Association to discuss how to use the toolkit and why it – and other resources on providing nuanced mental health care – are needed.

Vidyard Video

In this video, Dr. Awaad explores some of the origins of Islamophobia in the United States and how she came to do this work while in medical school. The travel ban affecting mostly Muslim countries has had a ripple effect on community members, she said. “The feeling is ‘My country isn’t named in the travel ban, but will I be next?’ ”

In addition to the fear and distrust fostered by the political climate are the challenges of abiding by the Islamic faith’s precepts.

“Patients will just do things on their own – and not consult their clinician,” Dr. Awaad said, referring to those might change the times in which they take medication during the sacred month of Ramadan because of fasting that is expected of observant Muslims. “It’s important for the patients to know that anyone acutely ill is exempt from fasting.” Medical- and faith-based consultation are important for these patients, Dr. Awaad said, pointing to a recent article that outlines best practices for treating patients with psychiatric disorders during Ramadan (Lancet Psychiatry. 2019 May 2. doi: 10.1016/S2215-0366[19]30161-0).

She also discussed “Islamophobia and Psychiatry” (Springer, 2019), a book she coedited that she said provides evidence of the detrimental effect that Islamophobia has on the mental health of Muslims.

Dr. Awaad is director of the Muslim Mental Health Lab and Wellness Program and codirector of the Diversity Clinic at Stanford (Calif.) University. Dr. Bandstra is assistant director of residency training in Stanford’s department of psychiatry and behavioral sciences. Dr. Awaad and Dr. Bandstra had no relevant disclosures.

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– A toolkit that seeks to help clinicians provide culturally and religiously informed mental health care for Muslim patients was officially launched at the annual meeting of the American Psychiatric Association.

Rania Awaad, MD, and Belinda S. Bandstra, MD, sat down at the annual meeting of the American Psychiatric Association to discuss how to use the toolkit and why it – and other resources on providing nuanced mental health care – are needed.

Vidyard Video

In this video, Dr. Awaad explores some of the origins of Islamophobia in the United States and how she came to do this work while in medical school. The travel ban affecting mostly Muslim countries has had a ripple effect on community members, she said. “The feeling is ‘My country isn’t named in the travel ban, but will I be next?’ ”

In addition to the fear and distrust fostered by the political climate are the challenges of abiding by the Islamic faith’s precepts.

“Patients will just do things on their own – and not consult their clinician,” Dr. Awaad said, referring to those might change the times in which they take medication during the sacred month of Ramadan because of fasting that is expected of observant Muslims. “It’s important for the patients to know that anyone acutely ill is exempt from fasting.” Medical- and faith-based consultation are important for these patients, Dr. Awaad said, pointing to a recent article that outlines best practices for treating patients with psychiatric disorders during Ramadan (Lancet Psychiatry. 2019 May 2. doi: 10.1016/S2215-0366[19]30161-0).

She also discussed “Islamophobia and Psychiatry” (Springer, 2019), a book she coedited that she said provides evidence of the detrimental effect that Islamophobia has on the mental health of Muslims.

Dr. Awaad is director of the Muslim Mental Health Lab and Wellness Program and codirector of the Diversity Clinic at Stanford (Calif.) University. Dr. Bandstra is assistant director of residency training in Stanford’s department of psychiatry and behavioral sciences. Dr. Awaad and Dr. Bandstra had no relevant disclosures.

 

– A toolkit that seeks to help clinicians provide culturally and religiously informed mental health care for Muslim patients was officially launched at the annual meeting of the American Psychiatric Association.

Rania Awaad, MD, and Belinda S. Bandstra, MD, sat down at the annual meeting of the American Psychiatric Association to discuss how to use the toolkit and why it – and other resources on providing nuanced mental health care – are needed.

Vidyard Video

In this video, Dr. Awaad explores some of the origins of Islamophobia in the United States and how she came to do this work while in medical school. The travel ban affecting mostly Muslim countries has had a ripple effect on community members, she said. “The feeling is ‘My country isn’t named in the travel ban, but will I be next?’ ”

In addition to the fear and distrust fostered by the political climate are the challenges of abiding by the Islamic faith’s precepts.

“Patients will just do things on their own – and not consult their clinician,” Dr. Awaad said, referring to those might change the times in which they take medication during the sacred month of Ramadan because of fasting that is expected of observant Muslims. “It’s important for the patients to know that anyone acutely ill is exempt from fasting.” Medical- and faith-based consultation are important for these patients, Dr. Awaad said, pointing to a recent article that outlines best practices for treating patients with psychiatric disorders during Ramadan (Lancet Psychiatry. 2019 May 2. doi: 10.1016/S2215-0366[19]30161-0).

She also discussed “Islamophobia and Psychiatry” (Springer, 2019), a book she coedited that she said provides evidence of the detrimental effect that Islamophobia has on the mental health of Muslims.

Dr. Awaad is director of the Muslim Mental Health Lab and Wellness Program and codirector of the Diversity Clinic at Stanford (Calif.) University. Dr. Bandstra is assistant director of residency training in Stanford’s department of psychiatry and behavioral sciences. Dr. Awaad and Dr. Bandstra had no relevant disclosures.

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More empathy for women

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At the risk of too much personal self-disclosure, I feel the need to write about my having developed more empathy for women. Having been described as a “manly man,” by a woman who feels she knows me, it has always been difficult for me to understand women. Fortunately, an experience I’ve had has given me more insight into women – shallow though it may still be.

Dr. Carl C. Bell

About a year ago, I had learned I had prostate carcinoma, which is now in remission – thanks to a proctectomy, radiation, and hormone therapy. The antitestosterone hormones I need to take for 2 years are turning me into an old woman, thus my newfound empathy.

After the surgery, I found myself leaking – something that I probably only experienced as a child and of which I have little memory. I now have some more empathy for the problems women have with leaking each month or in general – it is a constant preoccupation. The leuprolide shots I am taking are giving me hot flashes, causing me to be more emotional about things I really don’t understand, and apparently I am at risk for getting osteoporosis – all things that happen to women that have been mildly on my radar for years but for which I lacked direct and personal experience.

Since having my testosterone turned off by the leuprolide, my joints are more prone to aches and pains from various injuries over the years. Because I understand that “motion is lotion,” I have some control of this problem. However, the hormone therapy has greatly reduced my endurance, so my exercise tolerance is far more limited – I understand fatigue now. When I was telling another woman who feels she knows me about my experience, she told me it was hormones that made it more difficult to lose weight. And, I am gaining weight.

All in all, I believe my experience has given me more empathy for women, but I realize I still have a very long way to go. Nonetheless, I will continue in my quest to understand the opposite sex, as I am told “women hold up half the sky,” and I have always believed that to be true.

Fortunately, women are ascending in psychiatry and, with some serious dedication, the dearth of scientific understanding of women’s issues will be a thing of the past. I am hoping that women psychiatrists will answer questions that men never even thought of asking, and fill that void of knowledge that we men psychiatrists have in our testosterone-bathed brains.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

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At the risk of too much personal self-disclosure, I feel the need to write about my having developed more empathy for women. Having been described as a “manly man,” by a woman who feels she knows me, it has always been difficult for me to understand women. Fortunately, an experience I’ve had has given me more insight into women – shallow though it may still be.

Dr. Carl C. Bell

About a year ago, I had learned I had prostate carcinoma, which is now in remission – thanks to a proctectomy, radiation, and hormone therapy. The antitestosterone hormones I need to take for 2 years are turning me into an old woman, thus my newfound empathy.

After the surgery, I found myself leaking – something that I probably only experienced as a child and of which I have little memory. I now have some more empathy for the problems women have with leaking each month or in general – it is a constant preoccupation. The leuprolide shots I am taking are giving me hot flashes, causing me to be more emotional about things I really don’t understand, and apparently I am at risk for getting osteoporosis – all things that happen to women that have been mildly on my radar for years but for which I lacked direct and personal experience.

Since having my testosterone turned off by the leuprolide, my joints are more prone to aches and pains from various injuries over the years. Because I understand that “motion is lotion,” I have some control of this problem. However, the hormone therapy has greatly reduced my endurance, so my exercise tolerance is far more limited – I understand fatigue now. When I was telling another woman who feels she knows me about my experience, she told me it was hormones that made it more difficult to lose weight. And, I am gaining weight.

All in all, I believe my experience has given me more empathy for women, but I realize I still have a very long way to go. Nonetheless, I will continue in my quest to understand the opposite sex, as I am told “women hold up half the sky,” and I have always believed that to be true.

Fortunately, women are ascending in psychiatry and, with some serious dedication, the dearth of scientific understanding of women’s issues will be a thing of the past. I am hoping that women psychiatrists will answer questions that men never even thought of asking, and fill that void of knowledge that we men psychiatrists have in our testosterone-bathed brains.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

 

At the risk of too much personal self-disclosure, I feel the need to write about my having developed more empathy for women. Having been described as a “manly man,” by a woman who feels she knows me, it has always been difficult for me to understand women. Fortunately, an experience I’ve had has given me more insight into women – shallow though it may still be.

Dr. Carl C. Bell

About a year ago, I had learned I had prostate carcinoma, which is now in remission – thanks to a proctectomy, radiation, and hormone therapy. The antitestosterone hormones I need to take for 2 years are turning me into an old woman, thus my newfound empathy.

After the surgery, I found myself leaking – something that I probably only experienced as a child and of which I have little memory. I now have some more empathy for the problems women have with leaking each month or in general – it is a constant preoccupation. The leuprolide shots I am taking are giving me hot flashes, causing me to be more emotional about things I really don’t understand, and apparently I am at risk for getting osteoporosis – all things that happen to women that have been mildly on my radar for years but for which I lacked direct and personal experience.

Since having my testosterone turned off by the leuprolide, my joints are more prone to aches and pains from various injuries over the years. Because I understand that “motion is lotion,” I have some control of this problem. However, the hormone therapy has greatly reduced my endurance, so my exercise tolerance is far more limited – I understand fatigue now. When I was telling another woman who feels she knows me about my experience, she told me it was hormones that made it more difficult to lose weight. And, I am gaining weight.

All in all, I believe my experience has given me more empathy for women, but I realize I still have a very long way to go. Nonetheless, I will continue in my quest to understand the opposite sex, as I am told “women hold up half the sky,” and I have always believed that to be true.

Fortunately, women are ascending in psychiatry and, with some serious dedication, the dearth of scientific understanding of women’s issues will be a thing of the past. I am hoping that women psychiatrists will answer questions that men never even thought of asking, and fill that void of knowledge that we men psychiatrists have in our testosterone-bathed brains.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

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Report on newly recognized cause of dementia should be read widely

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Alzheimer’s disease is recognized as the most common cause of dementia, and many in the laity use the two terms almost interchangeably. However, there is increasing recognition that dementia in old age is a complex disorder, with mixed neuropathologies being the norm rather than the exception (Ann Neurol. 2018 Jan;83[1]:74-83).

Dr. Perminder Sachdev

Alzheimer’s disease (AD) and cerebrovascular pathologies are the most common, but another pathology is receiving increasing attention in relation to cognitive disorders in very old individuals – that related to the transactive response DNA binding protein of 43 kDa (TDP-43). This protein is expressed in most human tissues, including the brain, is localized mostly in nuclei, and binds to RNA and DNA as well as numerous proteins, with the role of regulating gene expression.

It has been known for nearly 2 decades that TDP-43 can become abnormally phosphorylated and translocated to the cytoplasm to produce a proteinopathy that forms the basis of a significant proportion of frontotemporal dementia (FTD) and the majority of amyotrophic lateral sclerosis. More recently, it has also been reported to be common in the brains of older people (over age 80 years) and associated with a cognitive disorder characterized by an amnestic picture that mimics AD. Since the protein deposition is predominantly in the limbic regions (amygdala, hippocampus, insula), it has been termed “‘limbic-predominant, age-related TDP-43 encephalopathy”, or LATE.

A recently convened international working group has published consensus criteria for LATE and provided guidelines for its staging. Community-based autopsy studies suggest that 20%-50% of people aged over 80 years have the neuropathologic change associated with LATE. The clinical presentation resembles amnestic dementia syndrome, much like AD. Both LATE and AD pathologies often occur in the same individual, but the relative predominance of one or the other varies greatly between individuals. The genetic risks of LATE overlap with those for FTD and AD, and other risk factors may also be shared with AD, which remains an area for further investigation. There are at present no specific biomarkers of LATE. It is associated with hippocampal sclerosis in some cases, which may be visible on MRI, but hippocampal sclerosis itself is not specific to TDP-43 pathology.

The LATE consensus working group report (Brain. 2019 Apr 30. doi: 10.1093/brain/awz099) underlines several gaps in our understanding of LATE and calls for systematic study of the causes of dementia – which may be nearly as common as AD in the very old. The report should be read widely and should remind us of the diverse pathologies that contribute to cognitive disorders, alone and in combination with one another.

Dr. Sachdev is Scientia Professor of Neuropsychiatry and codirector of the Center for Healthy Brain Aging at the University of New South Wales, Sydney; and clinical director of the Neuropsychiatric Institute at the Prince of Wales Hospital, also in Sydney. His major areas of research are drug-induced movement disorders, brain imaging, cognitive aging and dementia. Dr. Sachdev also served on the Neurocognitive Disorders Work Group of the DSM-5.

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Alzheimer’s disease is recognized as the most common cause of dementia, and many in the laity use the two terms almost interchangeably. However, there is increasing recognition that dementia in old age is a complex disorder, with mixed neuropathologies being the norm rather than the exception (Ann Neurol. 2018 Jan;83[1]:74-83).

Dr. Perminder Sachdev

Alzheimer’s disease (AD) and cerebrovascular pathologies are the most common, but another pathology is receiving increasing attention in relation to cognitive disorders in very old individuals – that related to the transactive response DNA binding protein of 43 kDa (TDP-43). This protein is expressed in most human tissues, including the brain, is localized mostly in nuclei, and binds to RNA and DNA as well as numerous proteins, with the role of regulating gene expression.

It has been known for nearly 2 decades that TDP-43 can become abnormally phosphorylated and translocated to the cytoplasm to produce a proteinopathy that forms the basis of a significant proportion of frontotemporal dementia (FTD) and the majority of amyotrophic lateral sclerosis. More recently, it has also been reported to be common in the brains of older people (over age 80 years) and associated with a cognitive disorder characterized by an amnestic picture that mimics AD. Since the protein deposition is predominantly in the limbic regions (amygdala, hippocampus, insula), it has been termed “‘limbic-predominant, age-related TDP-43 encephalopathy”, or LATE.

A recently convened international working group has published consensus criteria for LATE and provided guidelines for its staging. Community-based autopsy studies suggest that 20%-50% of people aged over 80 years have the neuropathologic change associated with LATE. The clinical presentation resembles amnestic dementia syndrome, much like AD. Both LATE and AD pathologies often occur in the same individual, but the relative predominance of one or the other varies greatly between individuals. The genetic risks of LATE overlap with those for FTD and AD, and other risk factors may also be shared with AD, which remains an area for further investigation. There are at present no specific biomarkers of LATE. It is associated with hippocampal sclerosis in some cases, which may be visible on MRI, but hippocampal sclerosis itself is not specific to TDP-43 pathology.

The LATE consensus working group report (Brain. 2019 Apr 30. doi: 10.1093/brain/awz099) underlines several gaps in our understanding of LATE and calls for systematic study of the causes of dementia – which may be nearly as common as AD in the very old. The report should be read widely and should remind us of the diverse pathologies that contribute to cognitive disorders, alone and in combination with one another.

Dr. Sachdev is Scientia Professor of Neuropsychiatry and codirector of the Center for Healthy Brain Aging at the University of New South Wales, Sydney; and clinical director of the Neuropsychiatric Institute at the Prince of Wales Hospital, also in Sydney. His major areas of research are drug-induced movement disorders, brain imaging, cognitive aging and dementia. Dr. Sachdev also served on the Neurocognitive Disorders Work Group of the DSM-5.

 

Alzheimer’s disease is recognized as the most common cause of dementia, and many in the laity use the two terms almost interchangeably. However, there is increasing recognition that dementia in old age is a complex disorder, with mixed neuropathologies being the norm rather than the exception (Ann Neurol. 2018 Jan;83[1]:74-83).

Dr. Perminder Sachdev

Alzheimer’s disease (AD) and cerebrovascular pathologies are the most common, but another pathology is receiving increasing attention in relation to cognitive disorders in very old individuals – that related to the transactive response DNA binding protein of 43 kDa (TDP-43). This protein is expressed in most human tissues, including the brain, is localized mostly in nuclei, and binds to RNA and DNA as well as numerous proteins, with the role of regulating gene expression.

It has been known for nearly 2 decades that TDP-43 can become abnormally phosphorylated and translocated to the cytoplasm to produce a proteinopathy that forms the basis of a significant proportion of frontotemporal dementia (FTD) and the majority of amyotrophic lateral sclerosis. More recently, it has also been reported to be common in the brains of older people (over age 80 years) and associated with a cognitive disorder characterized by an amnestic picture that mimics AD. Since the protein deposition is predominantly in the limbic regions (amygdala, hippocampus, insula), it has been termed “‘limbic-predominant, age-related TDP-43 encephalopathy”, or LATE.

A recently convened international working group has published consensus criteria for LATE and provided guidelines for its staging. Community-based autopsy studies suggest that 20%-50% of people aged over 80 years have the neuropathologic change associated with LATE. The clinical presentation resembles amnestic dementia syndrome, much like AD. Both LATE and AD pathologies often occur in the same individual, but the relative predominance of one or the other varies greatly between individuals. The genetic risks of LATE overlap with those for FTD and AD, and other risk factors may also be shared with AD, which remains an area for further investigation. There are at present no specific biomarkers of LATE. It is associated with hippocampal sclerosis in some cases, which may be visible on MRI, but hippocampal sclerosis itself is not specific to TDP-43 pathology.

The LATE consensus working group report (Brain. 2019 Apr 30. doi: 10.1093/brain/awz099) underlines several gaps in our understanding of LATE and calls for systematic study of the causes of dementia – which may be nearly as common as AD in the very old. The report should be read widely and should remind us of the diverse pathologies that contribute to cognitive disorders, alone and in combination with one another.

Dr. Sachdev is Scientia Professor of Neuropsychiatry and codirector of the Center for Healthy Brain Aging at the University of New South Wales, Sydney; and clinical director of the Neuropsychiatric Institute at the Prince of Wales Hospital, also in Sydney. His major areas of research are drug-induced movement disorders, brain imaging, cognitive aging and dementia. Dr. Sachdev also served on the Neurocognitive Disorders Work Group of the DSM-5.

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Hip-hop offers lens into psyche of black boys, men

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– The lyrics found in hip-hop can help mental health professionals understand the triumphs and trauma experienced by African American boys and men, Sarah Y. Vinson, MD, said at the annual meeting of the American Psychiatric Association. This understanding can enable clinicians to recognize hopelessness and pain in those patients that they otherwise might have missed.

In this video, Dr. Vinson said her session at the APA meeting looked at the history of hip-hop and focused on the perspectives embedded in the work of several artists/groups, including N.W.A, Tupac Shakur, Childish Gambino (aka Donald Glover), J. Cole, and Kendrick Lamar.

One of the take-home points for clinicians, Dr. Vinson said, is that hip-hop, an art form that has spread across the world, came out of resilience. Another is that suicidality in black men might not look the same as it does in other patients. “It doesn’t necessarily look like cutting your own wrists or having thoughts of killing yourself – it may look like reckless behaviors that put you at risk of being killed by somebody else.”

Dr. Vinson, who is triple boarded in child and adolescent, adult, and forensic psychiatry, is in private practice in Atlanta. She had no financial disclosures.

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– The lyrics found in hip-hop can help mental health professionals understand the triumphs and trauma experienced by African American boys and men, Sarah Y. Vinson, MD, said at the annual meeting of the American Psychiatric Association. This understanding can enable clinicians to recognize hopelessness and pain in those patients that they otherwise might have missed.

In this video, Dr. Vinson said her session at the APA meeting looked at the history of hip-hop and focused on the perspectives embedded in the work of several artists/groups, including N.W.A, Tupac Shakur, Childish Gambino (aka Donald Glover), J. Cole, and Kendrick Lamar.

One of the take-home points for clinicians, Dr. Vinson said, is that hip-hop, an art form that has spread across the world, came out of resilience. Another is that suicidality in black men might not look the same as it does in other patients. “It doesn’t necessarily look like cutting your own wrists or having thoughts of killing yourself – it may look like reckless behaviors that put you at risk of being killed by somebody else.”

Dr. Vinson, who is triple boarded in child and adolescent, adult, and forensic psychiatry, is in private practice in Atlanta. She had no financial disclosures.

– The lyrics found in hip-hop can help mental health professionals understand the triumphs and trauma experienced by African American boys and men, Sarah Y. Vinson, MD, said at the annual meeting of the American Psychiatric Association. This understanding can enable clinicians to recognize hopelessness and pain in those patients that they otherwise might have missed.

In this video, Dr. Vinson said her session at the APA meeting looked at the history of hip-hop and focused on the perspectives embedded in the work of several artists/groups, including N.W.A, Tupac Shakur, Childish Gambino (aka Donald Glover), J. Cole, and Kendrick Lamar.

One of the take-home points for clinicians, Dr. Vinson said, is that hip-hop, an art form that has spread across the world, came out of resilience. Another is that suicidality in black men might not look the same as it does in other patients. “It doesn’t necessarily look like cutting your own wrists or having thoughts of killing yourself – it may look like reckless behaviors that put you at risk of being killed by somebody else.”

Dr. Vinson, who is triple boarded in child and adolescent, adult, and forensic psychiatry, is in private practice in Atlanta. She had no financial disclosures.

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Opioid use associated with common bile duct dilation

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– Biliary duct dilation in the setting of an intact gallbladder and normal bilirubin levels was more common among those who used opioids, based on the results of a large, retrospective, single-center cohort study.

Patients were included in the study if they had a documented measurement for the diameter of the common bile duct, with no evidence of an obstructive lesion and a normal bilirubin level. The mean common bile duct diameter was significantly higher at 8.67 mm for 867 patients who used opioids, compared with 7.24 mm for 818 similar patients who did not use opioids (P less than .001). The association was strongest among opioid users with an intact gallbladder.

“Opiate use is associated with biliary dilation in the setting of normal bilirubin,” Monique Barakat, MD, a gastroenterologist at Stanford (Calif.) University, reported at the annual Digestive Disease Week. “Known opiate users with normal LFTs [liver function tests] may not require expensive and potentially risky endoscopic evaluation for biliary dilation.”

Dr. Barakat and senior author Subhas Banerjee, MD, professor of gastroenterology and hepatology at Stanford, decided to examine a possible association between biliary duct dilation and opioid use based on previous small clinical studies that found a possible association. Along with opioid status, Dr. Barakat and her coauthor also looked at patient age, cholecystectomy status, ethnicity, weight, and height for possible associations with bile duct diameter.

The researchers took a random 20% sample of adults seen for all causes in the ED at Stanford over a 5-year period. Using a health informatic platform based on the electronic medical record, they identified all patients who had received an abdominal CT or MRI. Patients were included in the study if they had a documented measurement for the diameter of the common bile duct, with no evidence of obstructive lesion and a normal bilirubin level.

Compared with 818 patients who did not use opioids, the 867 patients who used opioids had a significantly larger common bile duct diameter. Using 7 mm as the threshold for biliary duct enlargement, 84% of patients who used opioids had an enlarged common bile duct, compared with 27% of nonopioid users (P less than .001), said Dr. Barakat, recipient of an early investigator award for the study.

“We frequently get referrals for bile duct dilation with concern for more sinister causes of biliary duct dilation – stones, strictures, and malignancy,” said Dr. Barakat. Because of the increase in cross-sectional imaging via CT or MRI, bile duct dilation is being detected at increasingly higher rates.

Dr. Barakat said that about one-third of referrals to the therapeutic endoscopy clinic at Stanford are now for patients with biliary dilation and normal liver function tests. And similar increases are being “seen across all settings – so office, primary care clinic, inpatient, and most markedly, the emergency department. Coupled with this, the population is aging, and patients who present to each of these settings are more likely, if they are older, to undergo cross-sectional imaging.”

Other contributors to higher rates of bile duct dilation include increased rates of obesity and increased prevalence of nonalcoholic steatohepatitis (NASH). About 20% of individuals with NASH will also have abnormal LFTs, she said, and NASH can be the trigger for cross-sectional imaging.

For most of these patients with biliary duct dilation and normal LFTs, no obstructive process was found on endoscopic evaluation.

Although gastroenterology textbooks may say that bile duct diameter increases with age, Dr. Barakat and colleagues didn’t find this to be the case. Among nonopioid users in the study cohort, age did not predict of common bile duct diameter. Among the entire cohort, “Advancing age weakly predicts increased common bile duct diameter,” she said, suggesting that factors other than age along may drive increased bile duct diameter.

Limitations included the retrospective nature of the study, as well as the limitations of information from the electronic medical record. Also, interobserver variability may have come into play, as bile duct diameter measurements were made by multiple radiologists in the course of clinical care.

The study was funded by the National Institutes of Health. Dr. Barakat reported no relevant financial disclosures.

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– Biliary duct dilation in the setting of an intact gallbladder and normal bilirubin levels was more common among those who used opioids, based on the results of a large, retrospective, single-center cohort study.

Patients were included in the study if they had a documented measurement for the diameter of the common bile duct, with no evidence of an obstructive lesion and a normal bilirubin level. The mean common bile duct diameter was significantly higher at 8.67 mm for 867 patients who used opioids, compared with 7.24 mm for 818 similar patients who did not use opioids (P less than .001). The association was strongest among opioid users with an intact gallbladder.

“Opiate use is associated with biliary dilation in the setting of normal bilirubin,” Monique Barakat, MD, a gastroenterologist at Stanford (Calif.) University, reported at the annual Digestive Disease Week. “Known opiate users with normal LFTs [liver function tests] may not require expensive and potentially risky endoscopic evaluation for biliary dilation.”

Dr. Barakat and senior author Subhas Banerjee, MD, professor of gastroenterology and hepatology at Stanford, decided to examine a possible association between biliary duct dilation and opioid use based on previous small clinical studies that found a possible association. Along with opioid status, Dr. Barakat and her coauthor also looked at patient age, cholecystectomy status, ethnicity, weight, and height for possible associations with bile duct diameter.

The researchers took a random 20% sample of adults seen for all causes in the ED at Stanford over a 5-year period. Using a health informatic platform based on the electronic medical record, they identified all patients who had received an abdominal CT or MRI. Patients were included in the study if they had a documented measurement for the diameter of the common bile duct, with no evidence of obstructive lesion and a normal bilirubin level.

Compared with 818 patients who did not use opioids, the 867 patients who used opioids had a significantly larger common bile duct diameter. Using 7 mm as the threshold for biliary duct enlargement, 84% of patients who used opioids had an enlarged common bile duct, compared with 27% of nonopioid users (P less than .001), said Dr. Barakat, recipient of an early investigator award for the study.

“We frequently get referrals for bile duct dilation with concern for more sinister causes of biliary duct dilation – stones, strictures, and malignancy,” said Dr. Barakat. Because of the increase in cross-sectional imaging via CT or MRI, bile duct dilation is being detected at increasingly higher rates.

Dr. Barakat said that about one-third of referrals to the therapeutic endoscopy clinic at Stanford are now for patients with biliary dilation and normal liver function tests. And similar increases are being “seen across all settings – so office, primary care clinic, inpatient, and most markedly, the emergency department. Coupled with this, the population is aging, and patients who present to each of these settings are more likely, if they are older, to undergo cross-sectional imaging.”

Other contributors to higher rates of bile duct dilation include increased rates of obesity and increased prevalence of nonalcoholic steatohepatitis (NASH). About 20% of individuals with NASH will also have abnormal LFTs, she said, and NASH can be the trigger for cross-sectional imaging.

For most of these patients with biliary duct dilation and normal LFTs, no obstructive process was found on endoscopic evaluation.

Although gastroenterology textbooks may say that bile duct diameter increases with age, Dr. Barakat and colleagues didn’t find this to be the case. Among nonopioid users in the study cohort, age did not predict of common bile duct diameter. Among the entire cohort, “Advancing age weakly predicts increased common bile duct diameter,” she said, suggesting that factors other than age along may drive increased bile duct diameter.

Limitations included the retrospective nature of the study, as well as the limitations of information from the electronic medical record. Also, interobserver variability may have come into play, as bile duct diameter measurements were made by multiple radiologists in the course of clinical care.

The study was funded by the National Institutes of Health. Dr. Barakat reported no relevant financial disclosures.

 

– Biliary duct dilation in the setting of an intact gallbladder and normal bilirubin levels was more common among those who used opioids, based on the results of a large, retrospective, single-center cohort study.

Patients were included in the study if they had a documented measurement for the diameter of the common bile duct, with no evidence of an obstructive lesion and a normal bilirubin level. The mean common bile duct diameter was significantly higher at 8.67 mm for 867 patients who used opioids, compared with 7.24 mm for 818 similar patients who did not use opioids (P less than .001). The association was strongest among opioid users with an intact gallbladder.

“Opiate use is associated with biliary dilation in the setting of normal bilirubin,” Monique Barakat, MD, a gastroenterologist at Stanford (Calif.) University, reported at the annual Digestive Disease Week. “Known opiate users with normal LFTs [liver function tests] may not require expensive and potentially risky endoscopic evaluation for biliary dilation.”

Dr. Barakat and senior author Subhas Banerjee, MD, professor of gastroenterology and hepatology at Stanford, decided to examine a possible association between biliary duct dilation and opioid use based on previous small clinical studies that found a possible association. Along with opioid status, Dr. Barakat and her coauthor also looked at patient age, cholecystectomy status, ethnicity, weight, and height for possible associations with bile duct diameter.

The researchers took a random 20% sample of adults seen for all causes in the ED at Stanford over a 5-year period. Using a health informatic platform based on the electronic medical record, they identified all patients who had received an abdominal CT or MRI. Patients were included in the study if they had a documented measurement for the diameter of the common bile duct, with no evidence of obstructive lesion and a normal bilirubin level.

Compared with 818 patients who did not use opioids, the 867 patients who used opioids had a significantly larger common bile duct diameter. Using 7 mm as the threshold for biliary duct enlargement, 84% of patients who used opioids had an enlarged common bile duct, compared with 27% of nonopioid users (P less than .001), said Dr. Barakat, recipient of an early investigator award for the study.

“We frequently get referrals for bile duct dilation with concern for more sinister causes of biliary duct dilation – stones, strictures, and malignancy,” said Dr. Barakat. Because of the increase in cross-sectional imaging via CT or MRI, bile duct dilation is being detected at increasingly higher rates.

Dr. Barakat said that about one-third of referrals to the therapeutic endoscopy clinic at Stanford are now for patients with biliary dilation and normal liver function tests. And similar increases are being “seen across all settings – so office, primary care clinic, inpatient, and most markedly, the emergency department. Coupled with this, the population is aging, and patients who present to each of these settings are more likely, if they are older, to undergo cross-sectional imaging.”

Other contributors to higher rates of bile duct dilation include increased rates of obesity and increased prevalence of nonalcoholic steatohepatitis (NASH). About 20% of individuals with NASH will also have abnormal LFTs, she said, and NASH can be the trigger for cross-sectional imaging.

For most of these patients with biliary duct dilation and normal LFTs, no obstructive process was found on endoscopic evaluation.

Although gastroenterology textbooks may say that bile duct diameter increases with age, Dr. Barakat and colleagues didn’t find this to be the case. Among nonopioid users in the study cohort, age did not predict of common bile duct diameter. Among the entire cohort, “Advancing age weakly predicts increased common bile duct diameter,” she said, suggesting that factors other than age along may drive increased bile duct diameter.

Limitations included the retrospective nature of the study, as well as the limitations of information from the electronic medical record. Also, interobserver variability may have come into play, as bile duct diameter measurements were made by multiple radiologists in the course of clinical care.

The study was funded by the National Institutes of Health. Dr. Barakat reported no relevant financial disclosures.

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PPI metabolism may be altered in about one-third of bariatric surgery candidates

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– Rapid proton pump inhibitor (PPI) metabolism was present in nearly one-third of patients who underwent bariatric surgery, results from a small, single-center study showed. Patients who were fast metabolizers also exhibited a higher, although not significant, incidence of early marginal ulceration following Roux-en-Y gastric bypass.

Dr. Sabrena F. Noria

“Roux-en-Y gastric bypass [RYGB] is one of the most effective surgical approaches to mitigating obesity and its attendant comorbidities including diabetes, hypertension, hyperlipidemia, reflux, and sleep apnea,” lead study author Sabrena F. Noria, MD, PhD, said in an interview at the annual Digestive Disease Week. “However, as with all surgeries, there are associated risks, the more common of which is marginal ulceration, or ulcer formation at the gastrojejunostomy, which occurs at a rate of 1%-16%.”

Dr. Noria, surgical research director of the comprehensive weight management, metabolic/bariatric surgery program at the Ohio State University’s Wexner Medical Center, noted that marginal ulcers (MUs) are divided into early (within 90 days) and late (more than 90 days), based on their time of onset after surgery, and are usually diagnosed during upper endoscopy on postoperative patients who complain of epigastric pain, dysphagia, nausea/vomiting, and/or dehydration.

“Given that MUs are associated with multiple hospital readmissions for pain and dehydration, multiple diagnostic and therapeutic endoscopic procedures, and escalation in both antiulcer and analgesic medication, their clinical impact cannot be overstated, especially since RYGB is the second most commonly performed bariatric procedure in the U.S.,” she said. “Given that the majority of marginal ulcers occur early after surgery, bariatric surgery programs have adopted the prophylactic use of proton pump inhibitors for up to 90 days postoperatively. While studies have demonstrated up to a two-fold decrease in ulcer formation, sample heterogeneity, in terms of combining both early and late ulcers, make it difficult to determine the effect on early ulcer formation.”

In an effort to compare preoperative endoscopic findings and MU formation in patients with and without altered PPI metabolism, the researchers prospectively enrolled 94 bariatric patients to undergo genetic testing pertinent to drug metabolism for a comprehensive panel of medications using a commercially available pharmacogenetic testing kit for the activity of cytochrome P450 in drug metabolism. They grouped patients by whether they were fast or normal metabolizers, and compared preoperative endoscopic findings for patients on PPIs at baseline and rates of early (within 90 days) and late ulceration (between 90 and 180 days).

Dr. Noria reported that 28 patients (30%) in the entire cohort met criteria for being fast metabolizers. The researchers observed no differences in baseline body mass index, age, gender, or former smoking status between both groups. Among those treated with a PPI at baseline, fast metabolizers demonstrated a trend toward a higher incidence of gastritis on preoperative endoscopy, compared with controls (89% vs. 65%, respectively; P = .12), while detection of Helicobacter pylori and Barrett’s esophagus were nonsignificant between groups. Eight patients (17%) who underwent RYGB developed marginal ulcers within 6 months of the index operation, of which four (50%) were diagnosed within 90 days and categorized as early ulcers. Development of early ulceration was higher among fast metabolizers, compared with controls (13% vs. 6%), but this did not reach statistical significance (P = .60). All late ulcerations occurred within the control group.

“While none of our findings are statistically significant given the small sample size, there were two findings I found clinically compelling,” Dr. Noria said. “First, in the group of patients who were on PPIs preoperatively, we found a 24% increase in the presence of pathologically diagnosed gastritis in the rapid-metabolizer group, during screening endoscopy. This suggests that either these patients were undertreated or were not treated with the appropriate medication. The second interesting finding was an over doubling of early ulcer formation in the RYGB group who were rapid metabolizers. However, again I would caution against drawing any real conclusions as our sample size was not powered to detect any difference.”

She also acknowledged that the study was limited by the inability to determine the effect of confounders such as surgical approach and the lack of randomization.

Anahita D. Jalilvand, MD, a general surgery resident, postdoctoral research fellow, and PhD candidate, was instrumental to this study, Dr. Noria said.

The trial was sponsored by Pathnostics, a pharmacogenetic testing company, who covered the cost of the tests. The researchers reported having no financial disclosures.

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– Rapid proton pump inhibitor (PPI) metabolism was present in nearly one-third of patients who underwent bariatric surgery, results from a small, single-center study showed. Patients who were fast metabolizers also exhibited a higher, although not significant, incidence of early marginal ulceration following Roux-en-Y gastric bypass.

Dr. Sabrena F. Noria

“Roux-en-Y gastric bypass [RYGB] is one of the most effective surgical approaches to mitigating obesity and its attendant comorbidities including diabetes, hypertension, hyperlipidemia, reflux, and sleep apnea,” lead study author Sabrena F. Noria, MD, PhD, said in an interview at the annual Digestive Disease Week. “However, as with all surgeries, there are associated risks, the more common of which is marginal ulceration, or ulcer formation at the gastrojejunostomy, which occurs at a rate of 1%-16%.”

Dr. Noria, surgical research director of the comprehensive weight management, metabolic/bariatric surgery program at the Ohio State University’s Wexner Medical Center, noted that marginal ulcers (MUs) are divided into early (within 90 days) and late (more than 90 days), based on their time of onset after surgery, and are usually diagnosed during upper endoscopy on postoperative patients who complain of epigastric pain, dysphagia, nausea/vomiting, and/or dehydration.

“Given that MUs are associated with multiple hospital readmissions for pain and dehydration, multiple diagnostic and therapeutic endoscopic procedures, and escalation in both antiulcer and analgesic medication, their clinical impact cannot be overstated, especially since RYGB is the second most commonly performed bariatric procedure in the U.S.,” she said. “Given that the majority of marginal ulcers occur early after surgery, bariatric surgery programs have adopted the prophylactic use of proton pump inhibitors for up to 90 days postoperatively. While studies have demonstrated up to a two-fold decrease in ulcer formation, sample heterogeneity, in terms of combining both early and late ulcers, make it difficult to determine the effect on early ulcer formation.”

In an effort to compare preoperative endoscopic findings and MU formation in patients with and without altered PPI metabolism, the researchers prospectively enrolled 94 bariatric patients to undergo genetic testing pertinent to drug metabolism for a comprehensive panel of medications using a commercially available pharmacogenetic testing kit for the activity of cytochrome P450 in drug metabolism. They grouped patients by whether they were fast or normal metabolizers, and compared preoperative endoscopic findings for patients on PPIs at baseline and rates of early (within 90 days) and late ulceration (between 90 and 180 days).

Dr. Noria reported that 28 patients (30%) in the entire cohort met criteria for being fast metabolizers. The researchers observed no differences in baseline body mass index, age, gender, or former smoking status between both groups. Among those treated with a PPI at baseline, fast metabolizers demonstrated a trend toward a higher incidence of gastritis on preoperative endoscopy, compared with controls (89% vs. 65%, respectively; P = .12), while detection of Helicobacter pylori and Barrett’s esophagus were nonsignificant between groups. Eight patients (17%) who underwent RYGB developed marginal ulcers within 6 months of the index operation, of which four (50%) were diagnosed within 90 days and categorized as early ulcers. Development of early ulceration was higher among fast metabolizers, compared with controls (13% vs. 6%), but this did not reach statistical significance (P = .60). All late ulcerations occurred within the control group.

“While none of our findings are statistically significant given the small sample size, there were two findings I found clinically compelling,” Dr. Noria said. “First, in the group of patients who were on PPIs preoperatively, we found a 24% increase in the presence of pathologically diagnosed gastritis in the rapid-metabolizer group, during screening endoscopy. This suggests that either these patients were undertreated or were not treated with the appropriate medication. The second interesting finding was an over doubling of early ulcer formation in the RYGB group who were rapid metabolizers. However, again I would caution against drawing any real conclusions as our sample size was not powered to detect any difference.”

She also acknowledged that the study was limited by the inability to determine the effect of confounders such as surgical approach and the lack of randomization.

Anahita D. Jalilvand, MD, a general surgery resident, postdoctoral research fellow, and PhD candidate, was instrumental to this study, Dr. Noria said.

The trial was sponsored by Pathnostics, a pharmacogenetic testing company, who covered the cost of the tests. The researchers reported having no financial disclosures.

 

– Rapid proton pump inhibitor (PPI) metabolism was present in nearly one-third of patients who underwent bariatric surgery, results from a small, single-center study showed. Patients who were fast metabolizers also exhibited a higher, although not significant, incidence of early marginal ulceration following Roux-en-Y gastric bypass.

Dr. Sabrena F. Noria

“Roux-en-Y gastric bypass [RYGB] is one of the most effective surgical approaches to mitigating obesity and its attendant comorbidities including diabetes, hypertension, hyperlipidemia, reflux, and sleep apnea,” lead study author Sabrena F. Noria, MD, PhD, said in an interview at the annual Digestive Disease Week. “However, as with all surgeries, there are associated risks, the more common of which is marginal ulceration, or ulcer formation at the gastrojejunostomy, which occurs at a rate of 1%-16%.”

Dr. Noria, surgical research director of the comprehensive weight management, metabolic/bariatric surgery program at the Ohio State University’s Wexner Medical Center, noted that marginal ulcers (MUs) are divided into early (within 90 days) and late (more than 90 days), based on their time of onset after surgery, and are usually diagnosed during upper endoscopy on postoperative patients who complain of epigastric pain, dysphagia, nausea/vomiting, and/or dehydration.

“Given that MUs are associated with multiple hospital readmissions for pain and dehydration, multiple diagnostic and therapeutic endoscopic procedures, and escalation in both antiulcer and analgesic medication, their clinical impact cannot be overstated, especially since RYGB is the second most commonly performed bariatric procedure in the U.S.,” she said. “Given that the majority of marginal ulcers occur early after surgery, bariatric surgery programs have adopted the prophylactic use of proton pump inhibitors for up to 90 days postoperatively. While studies have demonstrated up to a two-fold decrease in ulcer formation, sample heterogeneity, in terms of combining both early and late ulcers, make it difficult to determine the effect on early ulcer formation.”

In an effort to compare preoperative endoscopic findings and MU formation in patients with and without altered PPI metabolism, the researchers prospectively enrolled 94 bariatric patients to undergo genetic testing pertinent to drug metabolism for a comprehensive panel of medications using a commercially available pharmacogenetic testing kit for the activity of cytochrome P450 in drug metabolism. They grouped patients by whether they were fast or normal metabolizers, and compared preoperative endoscopic findings for patients on PPIs at baseline and rates of early (within 90 days) and late ulceration (between 90 and 180 days).

Dr. Noria reported that 28 patients (30%) in the entire cohort met criteria for being fast metabolizers. The researchers observed no differences in baseline body mass index, age, gender, or former smoking status between both groups. Among those treated with a PPI at baseline, fast metabolizers demonstrated a trend toward a higher incidence of gastritis on preoperative endoscopy, compared with controls (89% vs. 65%, respectively; P = .12), while detection of Helicobacter pylori and Barrett’s esophagus were nonsignificant between groups. Eight patients (17%) who underwent RYGB developed marginal ulcers within 6 months of the index operation, of which four (50%) were diagnosed within 90 days and categorized as early ulcers. Development of early ulceration was higher among fast metabolizers, compared with controls (13% vs. 6%), but this did not reach statistical significance (P = .60). All late ulcerations occurred within the control group.

“While none of our findings are statistically significant given the small sample size, there were two findings I found clinically compelling,” Dr. Noria said. “First, in the group of patients who were on PPIs preoperatively, we found a 24% increase in the presence of pathologically diagnosed gastritis in the rapid-metabolizer group, during screening endoscopy. This suggests that either these patients were undertreated or were not treated with the appropriate medication. The second interesting finding was an over doubling of early ulcer formation in the RYGB group who were rapid metabolizers. However, again I would caution against drawing any real conclusions as our sample size was not powered to detect any difference.”

She also acknowledged that the study was limited by the inability to determine the effect of confounders such as surgical approach and the lack of randomization.

Anahita D. Jalilvand, MD, a general surgery resident, postdoctoral research fellow, and PhD candidate, was instrumental to this study, Dr. Noria said.

The trial was sponsored by Pathnostics, a pharmacogenetic testing company, who covered the cost of the tests. The researchers reported having no financial disclosures.

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About one-third of anxiety patients relapse after stopping antidepressants

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Patients taking antidepressants for anxiety disorders face a therapeutic dilemma when their anxiety goes into remission. Relapse is more likely in the absence of medication and, if they resume their antidepressant after relapse, some patients experience adverse events or drug resistance.

Jim Kling/MDedge News
Dr. Neeltje Batelaan

“It’s important that we realize that anxiety disorders can be treated effectively in the short term, but it’s very difficult to treat them for the long term. We know that within a year, it’s better to continue the medication. There’s a lack of data to give evidence-based advice after 1 year,” Neeltje Batelaan, MD, PhD, a psychiatrist and senior researcher at VU University Medical Center, Amsterdam, said in an interview.

Dr. Batelaan moderated a session at the annual meeting of the American Psychiatric Association on discontinuation of antidepressant medications in these patients.

Anxiety disorders can often be successfully treated with antidepressants, but their adverse effects can become less tolerable over time, especially after patients go into remission. When patients begin treatment, they are willing to endure side effects in the service of resolving their symptoms. But when they go into remission, “they want to get on with their lives, so their sexual side effects or their weight gain rates a lot worse,” Dr. Batelaan said.

A meta-analysis of 28 studies, with follow-up periods ranging from 8 to 52 weeks, found that the anxiety relapse risk after discontinuation of antidepressants was 36.4%, compared with 16.4% in those who stayed on medication. Even continuing antidepressants isn’t completely protective, she noted. The study found a number needed to treat of five to prevent one relapse.

Researchers at the VU University Medical Center developed a cognitive-behavioral therapy (CBT) regimen aimed at reducing anxiety relapses. In their study, 87 patients with a remitted anxiety disorder who wanted to stop their antidepressants were randomized to do so either with or without CBT intervention.

Unfortunately, the study had to be stopped when an interim analysis showed a lack of efficacy. In fact, patients who received CBT actually had higher relapse rates. Surprisingly, just 37% of patients succeeded in completely discontinuing medication, which hints at the inherent challenges of the transition.

“Unfortunately, building a CBT relapse prevention did not come true, but we learned some valuable lessons that will guide further studies,” Willemijn Scholten, PhD, a postdoc researcher at VU University Medical Center, said during one of the presentations.

In his presentation, Anton (Ton) Van Balkom, MD, PhD, professor of psychiatry at VU University Medical Center, recounted the case of a woman who had been functioning well with an antidepressant but grew tired of the sexual side effects. She carefully discontinued her medication under his guidance, but in 2 months she experienced her first panic attack in 30 years. Reintroducing the medication failed to resolve the issue, and it took years of effort before cognitive behavioral therapy resulted in a remission.

Further, a meta-analysis of nine studies showed that 17% of patients with remitted anxiety who went off and then restarted their antidepressants experienced tachycardia.

To help reduce tachycardia, Dr. Van Balkom suggested alternative options to antidepressants in less-complicated patients with anxiety, and to anticipate long-term use of antidepressants once those medications are employed.

Dr. Batelaan agreed with that assessment, drawing an analogy with type 2 diabetes. “You first start with a diet, and advise the patient to lose weight, and then if that’s not successful you go to [medication] and you realize it’s lifelong. Maybe we have to differentiate antidepressant therapies and [not start them until necessary]. But if you have to start them, realize that there’s a difficult decision waiting ahead.”

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Patients taking antidepressants for anxiety disorders face a therapeutic dilemma when their anxiety goes into remission. Relapse is more likely in the absence of medication and, if they resume their antidepressant after relapse, some patients experience adverse events or drug resistance.

Jim Kling/MDedge News
Dr. Neeltje Batelaan

“It’s important that we realize that anxiety disorders can be treated effectively in the short term, but it’s very difficult to treat them for the long term. We know that within a year, it’s better to continue the medication. There’s a lack of data to give evidence-based advice after 1 year,” Neeltje Batelaan, MD, PhD, a psychiatrist and senior researcher at VU University Medical Center, Amsterdam, said in an interview.

Dr. Batelaan moderated a session at the annual meeting of the American Psychiatric Association on discontinuation of antidepressant medications in these patients.

Anxiety disorders can often be successfully treated with antidepressants, but their adverse effects can become less tolerable over time, especially after patients go into remission. When patients begin treatment, they are willing to endure side effects in the service of resolving their symptoms. But when they go into remission, “they want to get on with their lives, so their sexual side effects or their weight gain rates a lot worse,” Dr. Batelaan said.

A meta-analysis of 28 studies, with follow-up periods ranging from 8 to 52 weeks, found that the anxiety relapse risk after discontinuation of antidepressants was 36.4%, compared with 16.4% in those who stayed on medication. Even continuing antidepressants isn’t completely protective, she noted. The study found a number needed to treat of five to prevent one relapse.

Researchers at the VU University Medical Center developed a cognitive-behavioral therapy (CBT) regimen aimed at reducing anxiety relapses. In their study, 87 patients with a remitted anxiety disorder who wanted to stop their antidepressants were randomized to do so either with or without CBT intervention.

Unfortunately, the study had to be stopped when an interim analysis showed a lack of efficacy. In fact, patients who received CBT actually had higher relapse rates. Surprisingly, just 37% of patients succeeded in completely discontinuing medication, which hints at the inherent challenges of the transition.

“Unfortunately, building a CBT relapse prevention did not come true, but we learned some valuable lessons that will guide further studies,” Willemijn Scholten, PhD, a postdoc researcher at VU University Medical Center, said during one of the presentations.

In his presentation, Anton (Ton) Van Balkom, MD, PhD, professor of psychiatry at VU University Medical Center, recounted the case of a woman who had been functioning well with an antidepressant but grew tired of the sexual side effects. She carefully discontinued her medication under his guidance, but in 2 months she experienced her first panic attack in 30 years. Reintroducing the medication failed to resolve the issue, and it took years of effort before cognitive behavioral therapy resulted in a remission.

Further, a meta-analysis of nine studies showed that 17% of patients with remitted anxiety who went off and then restarted their antidepressants experienced tachycardia.

To help reduce tachycardia, Dr. Van Balkom suggested alternative options to antidepressants in less-complicated patients with anxiety, and to anticipate long-term use of antidepressants once those medications are employed.

Dr. Batelaan agreed with that assessment, drawing an analogy with type 2 diabetes. “You first start with a diet, and advise the patient to lose weight, and then if that’s not successful you go to [medication] and you realize it’s lifelong. Maybe we have to differentiate antidepressant therapies and [not start them until necessary]. But if you have to start them, realize that there’s a difficult decision waiting ahead.”

 

Patients taking antidepressants for anxiety disorders face a therapeutic dilemma when their anxiety goes into remission. Relapse is more likely in the absence of medication and, if they resume their antidepressant after relapse, some patients experience adverse events or drug resistance.

Jim Kling/MDedge News
Dr. Neeltje Batelaan

“It’s important that we realize that anxiety disorders can be treated effectively in the short term, but it’s very difficult to treat them for the long term. We know that within a year, it’s better to continue the medication. There’s a lack of data to give evidence-based advice after 1 year,” Neeltje Batelaan, MD, PhD, a psychiatrist and senior researcher at VU University Medical Center, Amsterdam, said in an interview.

Dr. Batelaan moderated a session at the annual meeting of the American Psychiatric Association on discontinuation of antidepressant medications in these patients.

Anxiety disorders can often be successfully treated with antidepressants, but their adverse effects can become less tolerable over time, especially after patients go into remission. When patients begin treatment, they are willing to endure side effects in the service of resolving their symptoms. But when they go into remission, “they want to get on with their lives, so their sexual side effects or their weight gain rates a lot worse,” Dr. Batelaan said.

A meta-analysis of 28 studies, with follow-up periods ranging from 8 to 52 weeks, found that the anxiety relapse risk after discontinuation of antidepressants was 36.4%, compared with 16.4% in those who stayed on medication. Even continuing antidepressants isn’t completely protective, she noted. The study found a number needed to treat of five to prevent one relapse.

Researchers at the VU University Medical Center developed a cognitive-behavioral therapy (CBT) regimen aimed at reducing anxiety relapses. In their study, 87 patients with a remitted anxiety disorder who wanted to stop their antidepressants were randomized to do so either with or without CBT intervention.

Unfortunately, the study had to be stopped when an interim analysis showed a lack of efficacy. In fact, patients who received CBT actually had higher relapse rates. Surprisingly, just 37% of patients succeeded in completely discontinuing medication, which hints at the inherent challenges of the transition.

“Unfortunately, building a CBT relapse prevention did not come true, but we learned some valuable lessons that will guide further studies,” Willemijn Scholten, PhD, a postdoc researcher at VU University Medical Center, said during one of the presentations.

In his presentation, Anton (Ton) Van Balkom, MD, PhD, professor of psychiatry at VU University Medical Center, recounted the case of a woman who had been functioning well with an antidepressant but grew tired of the sexual side effects. She carefully discontinued her medication under his guidance, but in 2 months she experienced her first panic attack in 30 years. Reintroducing the medication failed to resolve the issue, and it took years of effort before cognitive behavioral therapy resulted in a remission.

Further, a meta-analysis of nine studies showed that 17% of patients with remitted anxiety who went off and then restarted their antidepressants experienced tachycardia.

To help reduce tachycardia, Dr. Van Balkom suggested alternative options to antidepressants in less-complicated patients with anxiety, and to anticipate long-term use of antidepressants once those medications are employed.

Dr. Batelaan agreed with that assessment, drawing an analogy with type 2 diabetes. “You first start with a diet, and advise the patient to lose weight, and then if that’s not successful you go to [medication] and you realize it’s lifelong. Maybe we have to differentiate antidepressant therapies and [not start them until necessary]. But if you have to start them, realize that there’s a difficult decision waiting ahead.”

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