International perspective on the new 2019 IDSA/ATS CAP guideline: A critical appraisal by a global expert panel. By Dr. Mathias Pletz, et al.



Development of an accurate bedside swallowing evaluation decision tree algorithm for detecting aspiration in acute respiratory failure survivors. By Dr. Marc Moss, et al.



How I Do It: Managing fatigue in patients with interstitial lung disease. By Dr. Marlies Wijsenbeek, et al.



Life-threatening and non-life-threatening complications associated with coughing: A scoping review. By Dr. Richard S. Irwin, MD, Master FCCP, et al.



Obstructive Sleep Apnea in Professional Transport Operations: Safety, Regulatory, and Economic Impact. By Dr. Indira Gurubhagavatula, et al.

International perspective on the new 2019 IDSA/ATS CAP guideline: A critical appraisal by a global expert panel. By Dr. Mathias Pletz, et al.



Development of an accurate bedside swallowing evaluation decision tree algorithm for detecting aspiration in acute respiratory failure survivors. By Dr. Marc Moss, et al.



How I Do It: Managing fatigue in patients with interstitial lung disease. By Dr. Marlies Wijsenbeek, et al.



Life-threatening and non-life-threatening complications associated with coughing: A scoping review. By Dr. Richard S. Irwin, MD, Master FCCP, et al.



Obstructive Sleep Apnea in Professional Transport Operations: Safety, Regulatory, and Economic Impact. By Dr. Indira Gurubhagavatula, et al.

International perspective on the new 2019 IDSA/ATS CAP guideline: A critical appraisal by a global expert panel. By Dr. Mathias Pletz, et al.



Development of an accurate bedside swallowing evaluation decision tree algorithm for detecting aspiration in acute respiratory failure survivors. By Dr. Marc Moss, et al.



How I Do It: Managing fatigue in patients with interstitial lung disease. By Dr. Marlies Wijsenbeek, et al.



Life-threatening and non-life-threatening complications associated with coughing: A scoping review. By Dr. Richard S. Irwin, MD, Master FCCP, et al.



Obstructive Sleep Apnea in Professional Transport Operations: Safety, Regulatory, and Economic Impact. By Dr. Indira Gurubhagavatula, et al.

CHEST and the American Thoracic Society (ATS) submitted joint comments regarding the proposed Medicare Physician Fee Schedule for 2021 to CMS Administrator Seema Verma on topics of direct interest to members. The letter focuses on:

Medicare payment for critical care services: Further to the joint letter from CHEST, ATS, and the Society of Critical Care Medicine to Department of Health and Human Services Secretary Azar (see article in September 2020 Washington Watchline), the concerns related to the proposed 8% reduction in reimbursement for critical care services are explained, particularly relating to the role of critical care providers during the pandemic. They call for waiving budget neutrality or utilizing the public health emergency declaration to ensure appropriate patient care.

E/M payment changes: ATS and CHEST voice support for the proposed changes to evaluation and management (E/M) office visits and the increased reimbursement for the cognitive component of E/M medicine. They urge CMS to use its authority to waive the budget neutrality requirements while implementing the E/M changes.

Adoption of RUC-recommended values for pulmonary services: They urge CMS to finalize values for specific pulmonary services while acknowledging thanks for the adoption of the Relative Value Scale Update Committee (RUC)-recommended physician work values for a range of Current Procedural Terminology codes.

Telehealth services: While commending CMS for actions related to telehealth to provide care during the pandemic, they suggest it is now appropriate to sunset the telehealth listing for critical care services as providers have acquired additional experience in treating COVID-19.

GPC1X descriptors and utilization projections: They urge CMS to clarify the descriptors and seek additional comments on primary and ongoing health-care services.

Watch for reports of ongoing efforts from CHEST as the fee schedule process continues. Details of other activities in support of CHEST members appear in the November issue of Washington Watchline.

Reprinted from the November 2020 issue of Washington Watchline.

CHEST and the American Thoracic Society (ATS) submitted joint comments regarding the proposed Medicare Physician Fee Schedule for 2021 to CMS Administrator Seema Verma on topics of direct interest to members. The letter focuses on:

Medicare payment for critical care services: Further to the joint letter from CHEST, ATS, and the Society of Critical Care Medicine to Department of Health and Human Services Secretary Azar (see article in September 2020 Washington Watchline), the concerns related to the proposed 8% reduction in reimbursement for critical care services are explained, particularly relating to the role of critical care providers during the pandemic. They call for waiving budget neutrality or utilizing the public health emergency declaration to ensure appropriate patient care.

E/M payment changes: ATS and CHEST voice support for the proposed changes to evaluation and management (E/M) office visits and the increased reimbursement for the cognitive component of E/M medicine. They urge CMS to use its authority to waive the budget neutrality requirements while implementing the E/M changes.

Adoption of RUC-recommended values for pulmonary services: They urge CMS to finalize values for specific pulmonary services while acknowledging thanks for the adoption of the Relative Value Scale Update Committee (RUC)-recommended physician work values for a range of Current Procedural Terminology codes.

Telehealth services: While commending CMS for actions related to telehealth to provide care during the pandemic, they suggest it is now appropriate to sunset the telehealth listing for critical care services as providers have acquired additional experience in treating COVID-19.

GPC1X descriptors and utilization projections: They urge CMS to clarify the descriptors and seek additional comments on primary and ongoing health-care services.

Watch for reports of ongoing efforts from CHEST as the fee schedule process continues. Details of other activities in support of CHEST members appear in the November issue of Washington Watchline.

Reprinted from the November 2020 issue of Washington Watchline.

CHEST and the American Thoracic Society (ATS) submitted joint comments regarding the proposed Medicare Physician Fee Schedule for 2021 to CMS Administrator Seema Verma on topics of direct interest to members. The letter focuses on:

Medicare payment for critical care services: Further to the joint letter from CHEST, ATS, and the Society of Critical Care Medicine to Department of Health and Human Services Secretary Azar (see article in September 2020 Washington Watchline), the concerns related to the proposed 8% reduction in reimbursement for critical care services are explained, particularly relating to the role of critical care providers during the pandemic. They call for waiving budget neutrality or utilizing the public health emergency declaration to ensure appropriate patient care.

E/M payment changes: ATS and CHEST voice support for the proposed changes to evaluation and management (E/M) office visits and the increased reimbursement for the cognitive component of E/M medicine. They urge CMS to use its authority to waive the budget neutrality requirements while implementing the E/M changes.

Adoption of RUC-recommended values for pulmonary services: They urge CMS to finalize values for specific pulmonary services while acknowledging thanks for the adoption of the Relative Value Scale Update Committee (RUC)-recommended physician work values for a range of Current Procedural Terminology codes.

Telehealth services: While commending CMS for actions related to telehealth to provide care during the pandemic, they suggest it is now appropriate to sunset the telehealth listing for critical care services as providers have acquired additional experience in treating COVID-19.

GPC1X descriptors and utilization projections: They urge CMS to clarify the descriptors and seek additional comments on primary and ongoing health-care services.

Watch for reports of ongoing efforts from CHEST as the fee schedule process continues. Details of other activities in support of CHEST members appear in the November issue of Washington Watchline.

Reprinted from the November 2020 issue of Washington Watchline.

The rate of injuries with needles and other sharp instruments among hospital staff jumped sharply in July, which suggests the need for safety instruction early in the academic year, researchers say.

Brandy Sites/Thinkstock.com

“The reason this is important is it gives us an idea of when the best time to intervene might be,” said Jonathan Zampella, MD, an assistant professor of dermatology at New York University.

The findings were published online Nov. 4 in a research letter in JAMA Surgery.

Hundreds of thousands of health care workers incur injuries with needles and other sharp instruments every year, which places them at risk for blood-borne infections.

“Especially amongst dermatologists, it’s not a question of if you get stuck, it’s a question of when,” Dr. Zampella said in an interview. “Most have been stuck at some point in their lives.”

Until now, studies of these injuries have mostly depended on surveys, he said. By contrast, for the current study, Dr. Zampella and colleagues used a dataset of injuries reported to NYU Langone Health’s Occupational Health Services.

They identified 5,395 such injuries that occurred between January 2000 and February 2020. The total number was similar among surgical and nonsurgical specialists, but the mean incident rate was 4.7 for every 10 people among the nonsurgical staff versus 9.4 for every 10 people in the surgical staff.

Dr. Zampella and colleagues further found that the highest rate of injury, at 16.0 incidents for every 10 people, occurred among urology house staff, followed by orthopedic surgery staff, with 14.1, and general surgery staff, with 14.0. The lowest staff rates were among psychiatrists (0.3), radiation oncologists (1.1), and neurologists (2.4).

But even some nonsurgical specialties had high rates. For example, the rate was 11.5 for pathology house staff and 11.3 for dermatology house staff.

Dr. Zampella said his first reaction to the data was, “What the heck? What are pathologists doing that they are getting needlestick injuries?

“But it makes sense,” he said. “Sometimes they do biopsies, and they do fine-needle aspirations – these kinds of things that we might not be paying as much attention to as we should.”

The finding suggests that nonsurgical specialists should receive more training in injury prevention, he said.

The training should be in person, and it should not just be for first-year residents. “Everybody needs to have refreshers on preventing needlesticks,” he said. “And we have to make sure everyone in the hospital is playing for the same team. Residents are learning, and if they see poor technique by one of their attendings, that’s something they may imitate.”

The study’s primary conclusion regards the importance of seasonality in needlestick and other injuries from sharp instruments.

Among house staff, 9.4% of the injuries occurred in July. The proportion then gradually rose to 10.5% in October before gradually going back down to a low of 6.2% in June.

The difference from one quarter to the next was statistically significant (P = .02).

July is when internships and residencies start, Dr. Zampella pointed out. Among the nonhouse staff, the rate was consistent throughout the year.

This suggests that the beginning of the academic year for trainees was the key factor driving the uptick in injuries, he said.

He said that residents are receiving instruction in injury prevention, but perhaps not at the right time of year. For example, dermatology residents at NYU are given a lecture in needlestick injury prevention in February.

Dr. Zampella has received personal fees from X4 pharmaceuticals. The other authors disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

The rate of injuries with needles and other sharp instruments among hospital staff jumped sharply in July, which suggests the need for safety instruction early in the academic year, researchers say.

Brandy Sites/Thinkstock.com

“The reason this is important is it gives us an idea of when the best time to intervene might be,” said Jonathan Zampella, MD, an assistant professor of dermatology at New York University.

The findings were published online Nov. 4 in a research letter in JAMA Surgery.

Hundreds of thousands of health care workers incur injuries with needles and other sharp instruments every year, which places them at risk for blood-borne infections.

“Especially amongst dermatologists, it’s not a question of if you get stuck, it’s a question of when,” Dr. Zampella said in an interview. “Most have been stuck at some point in their lives.”

Until now, studies of these injuries have mostly depended on surveys, he said. By contrast, for the current study, Dr. Zampella and colleagues used a dataset of injuries reported to NYU Langone Health’s Occupational Health Services.

They identified 5,395 such injuries that occurred between January 2000 and February 2020. The total number was similar among surgical and nonsurgical specialists, but the mean incident rate was 4.7 for every 10 people among the nonsurgical staff versus 9.4 for every 10 people in the surgical staff.

Dr. Zampella and colleagues further found that the highest rate of injury, at 16.0 incidents for every 10 people, occurred among urology house staff, followed by orthopedic surgery staff, with 14.1, and general surgery staff, with 14.0. The lowest staff rates were among psychiatrists (0.3), radiation oncologists (1.1), and neurologists (2.4).

But even some nonsurgical specialties had high rates. For example, the rate was 11.5 for pathology house staff and 11.3 for dermatology house staff.

Dr. Zampella said his first reaction to the data was, “What the heck? What are pathologists doing that they are getting needlestick injuries?

“But it makes sense,” he said. “Sometimes they do biopsies, and they do fine-needle aspirations – these kinds of things that we might not be paying as much attention to as we should.”

The finding suggests that nonsurgical specialists should receive more training in injury prevention, he said.

The training should be in person, and it should not just be for first-year residents. “Everybody needs to have refreshers on preventing needlesticks,” he said. “And we have to make sure everyone in the hospital is playing for the same team. Residents are learning, and if they see poor technique by one of their attendings, that’s something they may imitate.”

The study’s primary conclusion regards the importance of seasonality in needlestick and other injuries from sharp instruments.

Among house staff, 9.4% of the injuries occurred in July. The proportion then gradually rose to 10.5% in October before gradually going back down to a low of 6.2% in June.

The difference from one quarter to the next was statistically significant (P = .02).

July is when internships and residencies start, Dr. Zampella pointed out. Among the nonhouse staff, the rate was consistent throughout the year.

This suggests that the beginning of the academic year for trainees was the key factor driving the uptick in injuries, he said.

He said that residents are receiving instruction in injury prevention, but perhaps not at the right time of year. For example, dermatology residents at NYU are given a lecture in needlestick injury prevention in February.

Dr. Zampella has received personal fees from X4 pharmaceuticals. The other authors disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

The rate of injuries with needles and other sharp instruments among hospital staff jumped sharply in July, which suggests the need for safety instruction early in the academic year, researchers say.

Brandy Sites/Thinkstock.com

“The reason this is important is it gives us an idea of when the best time to intervene might be,” said Jonathan Zampella, MD, an assistant professor of dermatology at New York University.

The findings were published online Nov. 4 in a research letter in JAMA Surgery.

Hundreds of thousands of health care workers incur injuries with needles and other sharp instruments every year, which places them at risk for blood-borne infections.

“Especially amongst dermatologists, it’s not a question of if you get stuck, it’s a question of when,” Dr. Zampella said in an interview. “Most have been stuck at some point in their lives.”

Until now, studies of these injuries have mostly depended on surveys, he said. By contrast, for the current study, Dr. Zampella and colleagues used a dataset of injuries reported to NYU Langone Health’s Occupational Health Services.

They identified 5,395 such injuries that occurred between January 2000 and February 2020. The total number was similar among surgical and nonsurgical specialists, but the mean incident rate was 4.7 for every 10 people among the nonsurgical staff versus 9.4 for every 10 people in the surgical staff.

Dr. Zampella and colleagues further found that the highest rate of injury, at 16.0 incidents for every 10 people, occurred among urology house staff, followed by orthopedic surgery staff, with 14.1, and general surgery staff, with 14.0. The lowest staff rates were among psychiatrists (0.3), radiation oncologists (1.1), and neurologists (2.4).

But even some nonsurgical specialties had high rates. For example, the rate was 11.5 for pathology house staff and 11.3 for dermatology house staff.

Dr. Zampella said his first reaction to the data was, “What the heck? What are pathologists doing that they are getting needlestick injuries?

“But it makes sense,” he said. “Sometimes they do biopsies, and they do fine-needle aspirations – these kinds of things that we might not be paying as much attention to as we should.”

The finding suggests that nonsurgical specialists should receive more training in injury prevention, he said.

The training should be in person, and it should not just be for first-year residents. “Everybody needs to have refreshers on preventing needlesticks,” he said. “And we have to make sure everyone in the hospital is playing for the same team. Residents are learning, and if they see poor technique by one of their attendings, that’s something they may imitate.”

The study’s primary conclusion regards the importance of seasonality in needlestick and other injuries from sharp instruments.

Among house staff, 9.4% of the injuries occurred in July. The proportion then gradually rose to 10.5% in October before gradually going back down to a low of 6.2% in June.

The difference from one quarter to the next was statistically significant (P = .02).

July is when internships and residencies start, Dr. Zampella pointed out. Among the nonhouse staff, the rate was consistent throughout the year.

This suggests that the beginning of the academic year for trainees was the key factor driving the uptick in injuries, he said.

He said that residents are receiving instruction in injury prevention, but perhaps not at the right time of year. For example, dermatology residents at NYU are given a lecture in needlestick injury prevention in February.

Dr. Zampella has received personal fees from X4 pharmaceuticals. The other authors disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

After a 50-year hiatus, psychedelic drugs are undergoing a research renaissance. Roland R. Griffiths, PhD, professor in the Departments of Psychiatry and Neuroscience and the Oliver Lee McCabe III, Professor in the Neuropsychopharmacology of Consciousness, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Baltimore, discusses the status of these drugs in the United States and their potential to treat psychiatric disorders.

Classic psychedelics are compounds that bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include the naturally occurring compounds psilocybin, N,N-dimethyltryptamine (DMT, a component of ayahuasca) and mescaline (peyote cactus), as well as the synthesized compound lysergic acid diethylamide (LSD).

Other drugs, such as ketamine, are sometimes referred to as “psychedelics” because they can produce subjective experiences that are similar to those of people who receive classic psychedelics. However, unlike classic psychedelics, the effects of ketamine tend to be short lived. Ketamine also has addictive potential and can be lethal in high doses, which is not the case with psilocybin.

Another compound sometimes referred to as a “psychedelic” is 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy.” The Food and Drug Administration granted breakthrough approval for the study of MDMA for posttraumatic stress disorder (PTSD). FDA-approved registration trials are ongoing. MDMA differs from classic psychedelics in risk profile and pharmacology. In particular, MDMA was widely abused as part of the “rave culture,” while classic psychedelic agents do not lend themselves to that type of misuse.
 

What is the current legal status of psychedelic agents in the United States? Can clinicians prescribe them, or are they available only in a research setting?

All classic psychedelics are considered to be “Schedule 1” which means they are illegal to possess and use except for research and only if approved by the FDA and under licensure of the Drug Enforcement Administration (DEA), so they are not available for clinical use.

In anticipation of the possibility that phase 3 research may support the efficacy and safety of psilocybin for one or more medical or mental health disorders, our team has reviewed available evidence regarding its abuse liability and concluded that, if psilocybin were approved as medication, it could possibly be included in the Schedule IV category, with additional FDA-mandated risk management provisions. However, this is not yet the case.
 

Which psychedelic agents are under investigation in the United States, and for which indications?

Psilocybin is under investigation in our center, as well as elsewhere in the United States. We have previously found it to be effective for smoking cessation, and we are conducting another study that is currently recruiting volunteers for this indication. We are also recruiting volunteers for studies on the use of psilocybin for major depression, Alzheimer’s disease, and anorexia nervosa. Further information about our studies can be found on the Web site for our center, the Center for Psychedelic and Consciousness Research.

Two companies – the Usona Institute and COMPASS Pathways – have received FDA Breakthrough Therapy Designation for their programs seeking approval of psilocybin as a treatment major depressive disorder and treatment-resistant depression (TRD), respectively. In addition, an international multicenter study currently underway, which includes US centers in Houston, Baltimore, New York, San Diego, and Atlanta, is investigating psilocybin for TRD.

A number of studies, including one conducted at our center, have investigated psilocybin for depression and anxiety in patients with cancer and found it effective.

Additional research showed that psilocybin alleviated symptoms of cancer-related anxiety and depression, both in the short-term and 5 years later.

LSD has been studied and found promising in the treatment of alcohol use disorder. Additional studies of LSD that are being conducted in Basel Switzerland and at the University of Chicago are examining its impact on mood in healthy volunteers.

Ayahuasca has been studied extensively for depression and anxiety and is also currently under investigation for PTSD. We found that its use in a naturalistic group setting was associated with unintended improvements in depression and anxiety.

Lastly, a lesser-known psychedelic agent is Salvinorin A, which our center has been studying, is the psychoactive constituent of the Salvia divinorum plant. While this is not a “classic” psychedelic compound, it is nevertheless the focus of much scientific interest because its effects are mediated at opioid receptors, rather than 5-HT2A receptors, and may prove to be a novel nonaddictive opioid that may ultimately be a promising treatment for pain and addiction.
 

What is the typical treatment regimen for psychedelic agents?

It is hard to speak of a “treatment regimen” in agents that are not used in clinical practice. Ongoing clinical trials with psilocybin generally involve one or two 6- to 8-hour sessions involving the oral administration of a moderately high dose under psychologically supported conditions.

Based on the current evidence base, which agents show the most promise?

Psilocybin is currently the most promising classic psychedelic undergoing clinical trials.

Do psychedelics have to be administered in a controlled setting in order to be effective?

Although many people have had meaningful experiences whether inside or outside of a controlled setting, there are serious potential risks associated with use of psilocybin and other classic psychedelics. The safety of psilocybin has been established in clinical studies in which participants have been carefully screened physically and psychologically, are psychologically prepared before their first session, and are psychologically supported during and after sessions. In vulnerable individuals, psilocybin has been associated with enduring psychiatric problems and sometimes persisting visual perceptual conditions. When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others – including life-threatening risk. Thus, for safety reasons, the optimal environment for using these agents is in a controlled setting.

Do results differ between patients who have used psychedelic agents previously and those who have not?

We have not found any difference between psychedelic-naive volunteers and those who have used psychedelics in the past.

Do you provide patient education prior to treatment initiation?

All of our study participants are thoroughly screened for medical concerns or mental health history such as psychosis, which would preclude their participation. They are educated about the effects of these agents and what they might expect and typically receive several hours of psychological preparation before the first session. They are also provided with psychological support after sessions. Additionally, we spend time developing trust and rapport prior to the first session.

How durable are the effects of psychedelic treatment?

Studies in patients and healthy participants suggest that the positive effects of psilocybin are long lasting, with most individuals reporting positive changes in moods, attitudes, and behavior that they attribute to psilocybin and which endure months or years after the session. The qualities of the acute session experience can vary widely ranging from experiences of transcendence or psychological insight to experiences of intense anxiety or fear.

An enduring shift in worldview and sense of self, as well as psychological insight, may increase psychological flexibility, thereby allowing individuals to subsequently avoid maladaptive patterns of behavior or thought and to make more healthy choices.

Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experience of their lives.
 

Do participants experience any adverse effects? If so, how are they managed?

Sometimes, despite all the preparation, screening, and support we provide, some participants can have frightening experiences, such as fear and anxiety during the session. When that occurs, it is often shorted lived. The psychological preparation we provide before the session and the psychological support we provide during the session are important for managing such effects.

We provide support and encourage participants to stay with that experience, which may open to experiences of deep meaning or insight. A number of people report that these psychologically challenging states are a valuable part of the overall experience.

We conducted a survey of roughly 2,000 people who took high doses of psilocybin mushrooms and then had a challenging experience. About 10% reported they put themselves or others at risk of physical harm. Of more concern, of those whose experience occurred more than 1 year before, 8% sought treatment for enduring psychological symptoms. These findings underscore potential risks of psilocybin use but do not provide an estimate of the actual incidence of such effects.

Importantly, in our research at Johns Hopkins, we have not observed such effects in over 700 sessions that we have conducted with almost 400 participants, likely because we thoroughly screen and prepare participants and support them after they have completed the study. The potential for serious lasting harm represents a concern and points to the importance of adequate screening and aftercare.
 

What are the implications for future therapeutics?

We are living in exciting times, in terms of psychedelic research. The potential for a single treatment with a classic psychedelic to produce rapid and sustained therapeutic effects, possibly across a range of psychiatric conditions, is unprecedented in psychiatry. The effect appears to be an “inverse PTSD effect.”

In PTSD, a single exposure to a traumatic event can rewire the nervous system to the point that it produces enduring harm and toxicity. In the case of psychedelics, a single exposure appears to have enduring positive effects in worldview, mood, attitude, behavior, and overall life satisfaction. We can look forward to continued growth and expansion of this research including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.
 

A version of this article originally appeared on Medscape.com.

After a 50-year hiatus, psychedelic drugs are undergoing a research renaissance. Roland R. Griffiths, PhD, professor in the Departments of Psychiatry and Neuroscience and the Oliver Lee McCabe III, Professor in the Neuropsychopharmacology of Consciousness, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Baltimore, discusses the status of these drugs in the United States and their potential to treat psychiatric disorders.

Classic psychedelics are compounds that bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include the naturally occurring compounds psilocybin, N,N-dimethyltryptamine (DMT, a component of ayahuasca) and mescaline (peyote cactus), as well as the synthesized compound lysergic acid diethylamide (LSD).

Other drugs, such as ketamine, are sometimes referred to as “psychedelics” because they can produce subjective experiences that are similar to those of people who receive classic psychedelics. However, unlike classic psychedelics, the effects of ketamine tend to be short lived. Ketamine also has addictive potential and can be lethal in high doses, which is not the case with psilocybin.

Another compound sometimes referred to as a “psychedelic” is 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy.” The Food and Drug Administration granted breakthrough approval for the study of MDMA for posttraumatic stress disorder (PTSD). FDA-approved registration trials are ongoing. MDMA differs from classic psychedelics in risk profile and pharmacology. In particular, MDMA was widely abused as part of the “rave culture,” while classic psychedelic agents do not lend themselves to that type of misuse.
 

What is the current legal status of psychedelic agents in the United States? Can clinicians prescribe them, or are they available only in a research setting?

All classic psychedelics are considered to be “Schedule 1” which means they are illegal to possess and use except for research and only if approved by the FDA and under licensure of the Drug Enforcement Administration (DEA), so they are not available for clinical use.

In anticipation of the possibility that phase 3 research may support the efficacy and safety of psilocybin for one or more medical or mental health disorders, our team has reviewed available evidence regarding its abuse liability and concluded that, if psilocybin were approved as medication, it could possibly be included in the Schedule IV category, with additional FDA-mandated risk management provisions. However, this is not yet the case.
 

Which psychedelic agents are under investigation in the United States, and for which indications?

Psilocybin is under investigation in our center, as well as elsewhere in the United States. We have previously found it to be effective for smoking cessation, and we are conducting another study that is currently recruiting volunteers for this indication. We are also recruiting volunteers for studies on the use of psilocybin for major depression, Alzheimer’s disease, and anorexia nervosa. Further information about our studies can be found on the Web site for our center, the Center for Psychedelic and Consciousness Research.

Two companies – the Usona Institute and COMPASS Pathways – have received FDA Breakthrough Therapy Designation for their programs seeking approval of psilocybin as a treatment major depressive disorder and treatment-resistant depression (TRD), respectively. In addition, an international multicenter study currently underway, which includes US centers in Houston, Baltimore, New York, San Diego, and Atlanta, is investigating psilocybin for TRD.

A number of studies, including one conducted at our center, have investigated psilocybin for depression and anxiety in patients with cancer and found it effective.

Additional research showed that psilocybin alleviated symptoms of cancer-related anxiety and depression, both in the short-term and 5 years later.

LSD has been studied and found promising in the treatment of alcohol use disorder. Additional studies of LSD that are being conducted in Basel Switzerland and at the University of Chicago are examining its impact on mood in healthy volunteers.

Ayahuasca has been studied extensively for depression and anxiety and is also currently under investigation for PTSD. We found that its use in a naturalistic group setting was associated with unintended improvements in depression and anxiety.

Lastly, a lesser-known psychedelic agent is Salvinorin A, which our center has been studying, is the psychoactive constituent of the Salvia divinorum plant. While this is not a “classic” psychedelic compound, it is nevertheless the focus of much scientific interest because its effects are mediated at opioid receptors, rather than 5-HT2A receptors, and may prove to be a novel nonaddictive opioid that may ultimately be a promising treatment for pain and addiction.
 

What is the typical treatment regimen for psychedelic agents?

It is hard to speak of a “treatment regimen” in agents that are not used in clinical practice. Ongoing clinical trials with psilocybin generally involve one or two 6- to 8-hour sessions involving the oral administration of a moderately high dose under psychologically supported conditions.

Based on the current evidence base, which agents show the most promise?

Psilocybin is currently the most promising classic psychedelic undergoing clinical trials.

Do psychedelics have to be administered in a controlled setting in order to be effective?

Although many people have had meaningful experiences whether inside or outside of a controlled setting, there are serious potential risks associated with use of psilocybin and other classic psychedelics. The safety of psilocybin has been established in clinical studies in which participants have been carefully screened physically and psychologically, are psychologically prepared before their first session, and are psychologically supported during and after sessions. In vulnerable individuals, psilocybin has been associated with enduring psychiatric problems and sometimes persisting visual perceptual conditions. When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others – including life-threatening risk. Thus, for safety reasons, the optimal environment for using these agents is in a controlled setting.

Do results differ between patients who have used psychedelic agents previously and those who have not?

We have not found any difference between psychedelic-naive volunteers and those who have used psychedelics in the past.

Do you provide patient education prior to treatment initiation?

All of our study participants are thoroughly screened for medical concerns or mental health history such as psychosis, which would preclude their participation. They are educated about the effects of these agents and what they might expect and typically receive several hours of psychological preparation before the first session. They are also provided with psychological support after sessions. Additionally, we spend time developing trust and rapport prior to the first session.

How durable are the effects of psychedelic treatment?

Studies in patients and healthy participants suggest that the positive effects of psilocybin are long lasting, with most individuals reporting positive changes in moods, attitudes, and behavior that they attribute to psilocybin and which endure months or years after the session. The qualities of the acute session experience can vary widely ranging from experiences of transcendence or psychological insight to experiences of intense anxiety or fear.

An enduring shift in worldview and sense of self, as well as psychological insight, may increase psychological flexibility, thereby allowing individuals to subsequently avoid maladaptive patterns of behavior or thought and to make more healthy choices.

Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experience of their lives.
 

Do participants experience any adverse effects? If so, how are they managed?

Sometimes, despite all the preparation, screening, and support we provide, some participants can have frightening experiences, such as fear and anxiety during the session. When that occurs, it is often shorted lived. The psychological preparation we provide before the session and the psychological support we provide during the session are important for managing such effects.

We provide support and encourage participants to stay with that experience, which may open to experiences of deep meaning or insight. A number of people report that these psychologically challenging states are a valuable part of the overall experience.

We conducted a survey of roughly 2,000 people who took high doses of psilocybin mushrooms and then had a challenging experience. About 10% reported they put themselves or others at risk of physical harm. Of more concern, of those whose experience occurred more than 1 year before, 8% sought treatment for enduring psychological symptoms. These findings underscore potential risks of psilocybin use but do not provide an estimate of the actual incidence of such effects.

Importantly, in our research at Johns Hopkins, we have not observed such effects in over 700 sessions that we have conducted with almost 400 participants, likely because we thoroughly screen and prepare participants and support them after they have completed the study. The potential for serious lasting harm represents a concern and points to the importance of adequate screening and aftercare.
 

What are the implications for future therapeutics?

We are living in exciting times, in terms of psychedelic research. The potential for a single treatment with a classic psychedelic to produce rapid and sustained therapeutic effects, possibly across a range of psychiatric conditions, is unprecedented in psychiatry. The effect appears to be an “inverse PTSD effect.”

In PTSD, a single exposure to a traumatic event can rewire the nervous system to the point that it produces enduring harm and toxicity. In the case of psychedelics, a single exposure appears to have enduring positive effects in worldview, mood, attitude, behavior, and overall life satisfaction. We can look forward to continued growth and expansion of this research including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.
 

A version of this article originally appeared on Medscape.com.

After a 50-year hiatus, psychedelic drugs are undergoing a research renaissance. Roland R. Griffiths, PhD, professor in the Departments of Psychiatry and Neuroscience and the Oliver Lee McCabe III, Professor in the Neuropsychopharmacology of Consciousness, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Baltimore, discusses the status of these drugs in the United States and their potential to treat psychiatric disorders.

Classic psychedelics are compounds that bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include the naturally occurring compounds psilocybin, N,N-dimethyltryptamine (DMT, a component of ayahuasca) and mescaline (peyote cactus), as well as the synthesized compound lysergic acid diethylamide (LSD).

Other drugs, such as ketamine, are sometimes referred to as “psychedelics” because they can produce subjective experiences that are similar to those of people who receive classic psychedelics. However, unlike classic psychedelics, the effects of ketamine tend to be short lived. Ketamine also has addictive potential and can be lethal in high doses, which is not the case with psilocybin.

Another compound sometimes referred to as a “psychedelic” is 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy.” The Food and Drug Administration granted breakthrough approval for the study of MDMA for posttraumatic stress disorder (PTSD). FDA-approved registration trials are ongoing. MDMA differs from classic psychedelics in risk profile and pharmacology. In particular, MDMA was widely abused as part of the “rave culture,” while classic psychedelic agents do not lend themselves to that type of misuse.
 

What is the current legal status of psychedelic agents in the United States? Can clinicians prescribe them, or are they available only in a research setting?

All classic psychedelics are considered to be “Schedule 1” which means they are illegal to possess and use except for research and only if approved by the FDA and under licensure of the Drug Enforcement Administration (DEA), so they are not available for clinical use.

In anticipation of the possibility that phase 3 research may support the efficacy and safety of psilocybin for one or more medical or mental health disorders, our team has reviewed available evidence regarding its abuse liability and concluded that, if psilocybin were approved as medication, it could possibly be included in the Schedule IV category, with additional FDA-mandated risk management provisions. However, this is not yet the case.
 

Which psychedelic agents are under investigation in the United States, and for which indications?

Psilocybin is under investigation in our center, as well as elsewhere in the United States. We have previously found it to be effective for smoking cessation, and we are conducting another study that is currently recruiting volunteers for this indication. We are also recruiting volunteers for studies on the use of psilocybin for major depression, Alzheimer’s disease, and anorexia nervosa. Further information about our studies can be found on the Web site for our center, the Center for Psychedelic and Consciousness Research.

Two companies – the Usona Institute and COMPASS Pathways – have received FDA Breakthrough Therapy Designation for their programs seeking approval of psilocybin as a treatment major depressive disorder and treatment-resistant depression (TRD), respectively. In addition, an international multicenter study currently underway, which includes US centers in Houston, Baltimore, New York, San Diego, and Atlanta, is investigating psilocybin for TRD.

A number of studies, including one conducted at our center, have investigated psilocybin for depression and anxiety in patients with cancer and found it effective.

Additional research showed that psilocybin alleviated symptoms of cancer-related anxiety and depression, both in the short-term and 5 years later.

LSD has been studied and found promising in the treatment of alcohol use disorder. Additional studies of LSD that are being conducted in Basel Switzerland and at the University of Chicago are examining its impact on mood in healthy volunteers.

Ayahuasca has been studied extensively for depression and anxiety and is also currently under investigation for PTSD. We found that its use in a naturalistic group setting was associated with unintended improvements in depression and anxiety.

Lastly, a lesser-known psychedelic agent is Salvinorin A, which our center has been studying, is the psychoactive constituent of the Salvia divinorum plant. While this is not a “classic” psychedelic compound, it is nevertheless the focus of much scientific interest because its effects are mediated at opioid receptors, rather than 5-HT2A receptors, and may prove to be a novel nonaddictive opioid that may ultimately be a promising treatment for pain and addiction.
 

What is the typical treatment regimen for psychedelic agents?

It is hard to speak of a “treatment regimen” in agents that are not used in clinical practice. Ongoing clinical trials with psilocybin generally involve one or two 6- to 8-hour sessions involving the oral administration of a moderately high dose under psychologically supported conditions.

Based on the current evidence base, which agents show the most promise?

Psilocybin is currently the most promising classic psychedelic undergoing clinical trials.

Do psychedelics have to be administered in a controlled setting in order to be effective?

Although many people have had meaningful experiences whether inside or outside of a controlled setting, there are serious potential risks associated with use of psilocybin and other classic psychedelics. The safety of psilocybin has been established in clinical studies in which participants have been carefully screened physically and psychologically, are psychologically prepared before their first session, and are psychologically supported during and after sessions. In vulnerable individuals, psilocybin has been associated with enduring psychiatric problems and sometimes persisting visual perceptual conditions. When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others – including life-threatening risk. Thus, for safety reasons, the optimal environment for using these agents is in a controlled setting.

Do results differ between patients who have used psychedelic agents previously and those who have not?

We have not found any difference between psychedelic-naive volunteers and those who have used psychedelics in the past.

Do you provide patient education prior to treatment initiation?

All of our study participants are thoroughly screened for medical concerns or mental health history such as psychosis, which would preclude their participation. They are educated about the effects of these agents and what they might expect and typically receive several hours of psychological preparation before the first session. They are also provided with psychological support after sessions. Additionally, we spend time developing trust and rapport prior to the first session.

How durable are the effects of psychedelic treatment?

Studies in patients and healthy participants suggest that the positive effects of psilocybin are long lasting, with most individuals reporting positive changes in moods, attitudes, and behavior that they attribute to psilocybin and which endure months or years after the session. The qualities of the acute session experience can vary widely ranging from experiences of transcendence or psychological insight to experiences of intense anxiety or fear.

An enduring shift in worldview and sense of self, as well as psychological insight, may increase psychological flexibility, thereby allowing individuals to subsequently avoid maladaptive patterns of behavior or thought and to make more healthy choices.

Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experience of their lives.
 

Do participants experience any adverse effects? If so, how are they managed?

Sometimes, despite all the preparation, screening, and support we provide, some participants can have frightening experiences, such as fear and anxiety during the session. When that occurs, it is often shorted lived. The psychological preparation we provide before the session and the psychological support we provide during the session are important for managing such effects.

We provide support and encourage participants to stay with that experience, which may open to experiences of deep meaning or insight. A number of people report that these psychologically challenging states are a valuable part of the overall experience.

We conducted a survey of roughly 2,000 people who took high doses of psilocybin mushrooms and then had a challenging experience. About 10% reported they put themselves or others at risk of physical harm. Of more concern, of those whose experience occurred more than 1 year before, 8% sought treatment for enduring psychological symptoms. These findings underscore potential risks of psilocybin use but do not provide an estimate of the actual incidence of such effects.

Importantly, in our research at Johns Hopkins, we have not observed such effects in over 700 sessions that we have conducted with almost 400 participants, likely because we thoroughly screen and prepare participants and support them after they have completed the study. The potential for serious lasting harm represents a concern and points to the importance of adequate screening and aftercare.
 

What are the implications for future therapeutics?

We are living in exciting times, in terms of psychedelic research. The potential for a single treatment with a classic psychedelic to produce rapid and sustained therapeutic effects, possibly across a range of psychiatric conditions, is unprecedented in psychiatry. The effect appears to be an “inverse PTSD effect.”

In PTSD, a single exposure to a traumatic event can rewire the nervous system to the point that it produces enduring harm and toxicity. In the case of psychedelics, a single exposure appears to have enduring positive effects in worldview, mood, attitude, behavior, and overall life satisfaction. We can look forward to continued growth and expansion of this research including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.
 

A version of this article originally appeared on Medscape.com.

Late-onset epilepsy is linked to a substantial increased risk of subsequent dementia. Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy.

“This is an exciting area, as we are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other cohort studies are finding similar results, including the Veterans’ Health Study and the Framingham Study,” she added.

The study was published online Oct. 23 in Neurology
 

Bidirectional relationship?

Previous research has established that dementia is a risk factor for epilepsy, but recent studies also suggest an increased risk of incident dementia among patients with adult-onset epilepsy. Several risk factors for late-onset epilepsy, including diabetes and hypertension, also are risk factors for dementia. However, the effect of late-onset epilepsy on dementia risk in patients with these comorbidities has not been clarified.

To investigate, the researchers examined data from the Atherosclerosis Risk in Communities (ARIC) study. Participants include Black and White men and women from four U.S. communities. Baseline visits in this longitudinal cohort study began between 1987 and 1989, and follow-up included seven additional visits and regular phone calls.

The investigators identified participants with late-onset epilepsy by searching for Medicare claims related to seizures or epilepsy filed between 1991 and 2015. Those with two or more such claims and age of onset of 67 years or greater were considered to have late-onset epilepsy. Participants with preexisting conditions such as brain tumors or multiple sclerosis were excluded.

ARIC participants who presented in person for visits 2, 4, 5, and 6 underwent cognitive testing with the Delayed Word Recall Test, the Digit Symbol Substitution Test, and the Word Fluency Test.

Testing at visits 5 and 6 also included other tests, such as the Mini-Mental State Examination, the Boston Naming test, and the Wechsler Memory Scale-III. Dr. Johnson and colleagues excluded data for visit 7 from the analysis because dementia adjudication was not yet complete.

The researchers identified participants with dementia using data from visits 5 and 6 and ascertained time of dementia onset through participant and informant interviews, phone calls, and hospital discharge data. Participants also were screened for mild cognitive impairment (MCI) at visits 5 and 6.

Data were analyzed using a Cox proportional hazards model and multinomial logistic regression. In subsequent analyses, researchers adjusted the data for age, sex, race, smoking status, alcohol use, hypertension, diabetes, body mass index (BMI), APOE4 status, and prevalent stroke.

The researchers found that of 9,033 study participants, 671 had late-onset epilepsy. The late-onset epilepsy group was older at baseline (56.5 vs. 55.1 years) and more likely to have hypertension (38.9% vs. 33.3%), diabetes (16.1% vs. 9.6%), and two alleles of APOE4 genotype (3.9% vs. 2.5%), compared with those without the disorder.

In all, 1,687 participants developed dementia during follow-up. The rate of incident dementia was 41.6% in participants with late-onset epilepsy and 16.8% in participants without late-onset epilepsy. The adjusted hazard ratio of subsequent dementia in participants with late-onset epilepsy versus those without the disorder was 3.05 (95% confidence interval, 2.65-3.51).

The median time to dementia ascertainment after late-onset epilepsy was 3.66 years.
 

Counterintuitive finding

The relationship between late-onset epilepsy and subsequent dementia was stronger in patients without stroke. The investigators offered a possible explanation for this counterintuitive finding. “We observed an interaction between [late-onset epilepsy] and stroke, with a lower (but still substantial) association between [late-onset epilepsy] and dementia in those with a history of stroke. This may be due to the known strong association between stroke and dementia, which may wash out the contributions of [late-onset epilepsy] to cognitive impairment,” the researchers wrote.

“There may also be under-capturing of dementia diagnoses among participants with stroke in the ascertainment from [Centers for Medicare & Medicaid Services] codes, as physicians may be reluctant to make a separate code for ‘dementia’ in those with cognitive impairment after stroke,” they added.

When the researchers restricted the analysis only to participants who attended visits 5 and 6 and had late-onset epilepsy ascertainment available, they found that the relative risk ratio for dementia at visit 6 was 2.90 (95% CI, 1.22-6.92; P = .009). The RRR for MCI was 0.97 (95% CI, 0.39-2.38; P = .803). The greater functional impairment in patients with late-onset epilepsy may explain the lack of a relationship between late-onset epilepsy and MCI.

“It will be important for neurologists to be aware of the possibility of cognitive impairment following late-onset epilepsy and to check in with patients and family members to see if there are concerns,” said Dr. Johnson.

“We should also be talking about the importance of lowering other risk factors for dementia by making sure cardiovascular risk factors are controlled and encouraging physical and cognitive activity,” she added.

The results require confirmation in a clinical population, the investigators noted. In addition, future research is necessary to clarify whether seizures directly increase the risk of dementia or whether shared neuropathology between epilepsy and dementia explains the risk.

“In the near future, I plan to enroll participants with late-onset epilepsy in an observational study to better understand factors that may contribute to cognitive change. Collaborations will be key as we seek to further understand what causes these changes and what could be done to prevent them,” Dr. Johnson added.
 

Strengths and weaknesses

In an accompanying editorial, W. Allen Hauser, MD, professor emeritus of neurology and epidemiology at Columbia University in New York, and colleagues noted that the findings support a bidirectional relationship between dementia and epilepsy, adding that accumulation of amyloid beta peptide is a plausible underlying pathophysiology that may explain this relationship.

Future research should clarify the effect of factors such as seizure type, seizure frequency, and age of onset on the risk of dementia among patients with epilepsy, the editorialists wrote. Such investigations could help elucidate the underlying mechanisms of these conditions and help to improve treatment, they added.

Commenting on the findings, Ilo Leppik, MD, professor of neurology and pharmacy at the University of Minnesota in Minneapolis described the research as “a very well-done study by qualified researchers in the field. … For the last century, medicine has unfortunately become compartmentalized by specialty and then subspecialty. The brain and disorders of the brain do not recognize these silos. … It is not a stretch of the known science to begin to understand that epilepsy and dementia have common anatomical and physiological underpinnings.”

The long period of prospectively gathering data and the measurement of cognitive function through various modalities are among the study’s great strengths, said Dr. Leppik. However, the study’s weakness is its reliance on Medicare claims data, which mainly would reflect convulsive seizures.

“What is missing is how many persons had subtle focal-unaware seizures that may not be identified unless a careful history is taken,” said Dr. Leppik. “Thus, this study likely underestimates the frequency of epilepsy.”

Neurologists who evaluate a person with early dementia should be on the lookout for a history of subtle seizures, said Dr. Leppik. Animal studies suggest treatment with levetiracetam or brivaracetam may slow the course of dementia, and a clinical study in participants with early dementia is underway.

“Treatment with an antiseizure drug may prove to be beneficial, especially if evidence for the presence of subtle epilepsy can be found,” Dr. Leppik added.

Greater collaboration between epileptologists and dementia specialists and larger studies of antiseizure drugs are necessary, he noted. “These studies can incorporate sophisticated structural and biochemical [analyses] to better identify the relationships between brain mechanisms that likely underlie both seizures and dementia. The ultimate promise is that early treatment of seizures may alter the course of dementia,” Dr. Leppik said.

The study by Dr. Johnson and colleagues was supported by a contract from the National Institute on Aging; ARIC from the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. The authors and Dr. Leppik have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Late-onset epilepsy is linked to a substantial increased risk of subsequent dementia. Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy.

“This is an exciting area, as we are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other cohort studies are finding similar results, including the Veterans’ Health Study and the Framingham Study,” she added.

The study was published online Oct. 23 in Neurology
 

Bidirectional relationship?

Previous research has established that dementia is a risk factor for epilepsy, but recent studies also suggest an increased risk of incident dementia among patients with adult-onset epilepsy. Several risk factors for late-onset epilepsy, including diabetes and hypertension, also are risk factors for dementia. However, the effect of late-onset epilepsy on dementia risk in patients with these comorbidities has not been clarified.

To investigate, the researchers examined data from the Atherosclerosis Risk in Communities (ARIC) study. Participants include Black and White men and women from four U.S. communities. Baseline visits in this longitudinal cohort study began between 1987 and 1989, and follow-up included seven additional visits and regular phone calls.

The investigators identified participants with late-onset epilepsy by searching for Medicare claims related to seizures or epilepsy filed between 1991 and 2015. Those with two or more such claims and age of onset of 67 years or greater were considered to have late-onset epilepsy. Participants with preexisting conditions such as brain tumors or multiple sclerosis were excluded.

ARIC participants who presented in person for visits 2, 4, 5, and 6 underwent cognitive testing with the Delayed Word Recall Test, the Digit Symbol Substitution Test, and the Word Fluency Test.

Testing at visits 5 and 6 also included other tests, such as the Mini-Mental State Examination, the Boston Naming test, and the Wechsler Memory Scale-III. Dr. Johnson and colleagues excluded data for visit 7 from the analysis because dementia adjudication was not yet complete.

The researchers identified participants with dementia using data from visits 5 and 6 and ascertained time of dementia onset through participant and informant interviews, phone calls, and hospital discharge data. Participants also were screened for mild cognitive impairment (MCI) at visits 5 and 6.

Data were analyzed using a Cox proportional hazards model and multinomial logistic regression. In subsequent analyses, researchers adjusted the data for age, sex, race, smoking status, alcohol use, hypertension, diabetes, body mass index (BMI), APOE4 status, and prevalent stroke.

The researchers found that of 9,033 study participants, 671 had late-onset epilepsy. The late-onset epilepsy group was older at baseline (56.5 vs. 55.1 years) and more likely to have hypertension (38.9% vs. 33.3%), diabetes (16.1% vs. 9.6%), and two alleles of APOE4 genotype (3.9% vs. 2.5%), compared with those without the disorder.

In all, 1,687 participants developed dementia during follow-up. The rate of incident dementia was 41.6% in participants with late-onset epilepsy and 16.8% in participants without late-onset epilepsy. The adjusted hazard ratio of subsequent dementia in participants with late-onset epilepsy versus those without the disorder was 3.05 (95% confidence interval, 2.65-3.51).

The median time to dementia ascertainment after late-onset epilepsy was 3.66 years.
 

Counterintuitive finding

The relationship between late-onset epilepsy and subsequent dementia was stronger in patients without stroke. The investigators offered a possible explanation for this counterintuitive finding. “We observed an interaction between [late-onset epilepsy] and stroke, with a lower (but still substantial) association between [late-onset epilepsy] and dementia in those with a history of stroke. This may be due to the known strong association between stroke and dementia, which may wash out the contributions of [late-onset epilepsy] to cognitive impairment,” the researchers wrote.

“There may also be under-capturing of dementia diagnoses among participants with stroke in the ascertainment from [Centers for Medicare & Medicaid Services] codes, as physicians may be reluctant to make a separate code for ‘dementia’ in those with cognitive impairment after stroke,” they added.

When the researchers restricted the analysis only to participants who attended visits 5 and 6 and had late-onset epilepsy ascertainment available, they found that the relative risk ratio for dementia at visit 6 was 2.90 (95% CI, 1.22-6.92; P = .009). The RRR for MCI was 0.97 (95% CI, 0.39-2.38; P = .803). The greater functional impairment in patients with late-onset epilepsy may explain the lack of a relationship between late-onset epilepsy and MCI.

“It will be important for neurologists to be aware of the possibility of cognitive impairment following late-onset epilepsy and to check in with patients and family members to see if there are concerns,” said Dr. Johnson.

“We should also be talking about the importance of lowering other risk factors for dementia by making sure cardiovascular risk factors are controlled and encouraging physical and cognitive activity,” she added.

The results require confirmation in a clinical population, the investigators noted. In addition, future research is necessary to clarify whether seizures directly increase the risk of dementia or whether shared neuropathology between epilepsy and dementia explains the risk.

“In the near future, I plan to enroll participants with late-onset epilepsy in an observational study to better understand factors that may contribute to cognitive change. Collaborations will be key as we seek to further understand what causes these changes and what could be done to prevent them,” Dr. Johnson added.
 

Strengths and weaknesses

In an accompanying editorial, W. Allen Hauser, MD, professor emeritus of neurology and epidemiology at Columbia University in New York, and colleagues noted that the findings support a bidirectional relationship between dementia and epilepsy, adding that accumulation of amyloid beta peptide is a plausible underlying pathophysiology that may explain this relationship.

Future research should clarify the effect of factors such as seizure type, seizure frequency, and age of onset on the risk of dementia among patients with epilepsy, the editorialists wrote. Such investigations could help elucidate the underlying mechanisms of these conditions and help to improve treatment, they added.

Commenting on the findings, Ilo Leppik, MD, professor of neurology and pharmacy at the University of Minnesota in Minneapolis described the research as “a very well-done study by qualified researchers in the field. … For the last century, medicine has unfortunately become compartmentalized by specialty and then subspecialty. The brain and disorders of the brain do not recognize these silos. … It is not a stretch of the known science to begin to understand that epilepsy and dementia have common anatomical and physiological underpinnings.”

The long period of prospectively gathering data and the measurement of cognitive function through various modalities are among the study’s great strengths, said Dr. Leppik. However, the study’s weakness is its reliance on Medicare claims data, which mainly would reflect convulsive seizures.

“What is missing is how many persons had subtle focal-unaware seizures that may not be identified unless a careful history is taken,” said Dr. Leppik. “Thus, this study likely underestimates the frequency of epilepsy.”

Neurologists who evaluate a person with early dementia should be on the lookout for a history of subtle seizures, said Dr. Leppik. Animal studies suggest treatment with levetiracetam or brivaracetam may slow the course of dementia, and a clinical study in participants with early dementia is underway.

“Treatment with an antiseizure drug may prove to be beneficial, especially if evidence for the presence of subtle epilepsy can be found,” Dr. Leppik added.

Greater collaboration between epileptologists and dementia specialists and larger studies of antiseizure drugs are necessary, he noted. “These studies can incorporate sophisticated structural and biochemical [analyses] to better identify the relationships between brain mechanisms that likely underlie both seizures and dementia. The ultimate promise is that early treatment of seizures may alter the course of dementia,” Dr. Leppik said.

The study by Dr. Johnson and colleagues was supported by a contract from the National Institute on Aging; ARIC from the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. The authors and Dr. Leppik have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Late-onset epilepsy is linked to a substantial increased risk of subsequent dementia. Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy.

“This is an exciting area, as we are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other cohort studies are finding similar results, including the Veterans’ Health Study and the Framingham Study,” she added.

The study was published online Oct. 23 in Neurology
 

Bidirectional relationship?

Previous research has established that dementia is a risk factor for epilepsy, but recent studies also suggest an increased risk of incident dementia among patients with adult-onset epilepsy. Several risk factors for late-onset epilepsy, including diabetes and hypertension, also are risk factors for dementia. However, the effect of late-onset epilepsy on dementia risk in patients with these comorbidities has not been clarified.

To investigate, the researchers examined data from the Atherosclerosis Risk in Communities (ARIC) study. Participants include Black and White men and women from four U.S. communities. Baseline visits in this longitudinal cohort study began between 1987 and 1989, and follow-up included seven additional visits and regular phone calls.

The investigators identified participants with late-onset epilepsy by searching for Medicare claims related to seizures or epilepsy filed between 1991 and 2015. Those with two or more such claims and age of onset of 67 years or greater were considered to have late-onset epilepsy. Participants with preexisting conditions such as brain tumors or multiple sclerosis were excluded.

ARIC participants who presented in person for visits 2, 4, 5, and 6 underwent cognitive testing with the Delayed Word Recall Test, the Digit Symbol Substitution Test, and the Word Fluency Test.

Testing at visits 5 and 6 also included other tests, such as the Mini-Mental State Examination, the Boston Naming test, and the Wechsler Memory Scale-III. Dr. Johnson and colleagues excluded data for visit 7 from the analysis because dementia adjudication was not yet complete.

The researchers identified participants with dementia using data from visits 5 and 6 and ascertained time of dementia onset through participant and informant interviews, phone calls, and hospital discharge data. Participants also were screened for mild cognitive impairment (MCI) at visits 5 and 6.

Data were analyzed using a Cox proportional hazards model and multinomial logistic regression. In subsequent analyses, researchers adjusted the data for age, sex, race, smoking status, alcohol use, hypertension, diabetes, body mass index (BMI), APOE4 status, and prevalent stroke.

The researchers found that of 9,033 study participants, 671 had late-onset epilepsy. The late-onset epilepsy group was older at baseline (56.5 vs. 55.1 years) and more likely to have hypertension (38.9% vs. 33.3%), diabetes (16.1% vs. 9.6%), and two alleles of APOE4 genotype (3.9% vs. 2.5%), compared with those without the disorder.

In all, 1,687 participants developed dementia during follow-up. The rate of incident dementia was 41.6% in participants with late-onset epilepsy and 16.8% in participants without late-onset epilepsy. The adjusted hazard ratio of subsequent dementia in participants with late-onset epilepsy versus those without the disorder was 3.05 (95% confidence interval, 2.65-3.51).

The median time to dementia ascertainment after late-onset epilepsy was 3.66 years.
 

Counterintuitive finding

The relationship between late-onset epilepsy and subsequent dementia was stronger in patients without stroke. The investigators offered a possible explanation for this counterintuitive finding. “We observed an interaction between [late-onset epilepsy] and stroke, with a lower (but still substantial) association between [late-onset epilepsy] and dementia in those with a history of stroke. This may be due to the known strong association between stroke and dementia, which may wash out the contributions of [late-onset epilepsy] to cognitive impairment,” the researchers wrote.

“There may also be under-capturing of dementia diagnoses among participants with stroke in the ascertainment from [Centers for Medicare & Medicaid Services] codes, as physicians may be reluctant to make a separate code for ‘dementia’ in those with cognitive impairment after stroke,” they added.

When the researchers restricted the analysis only to participants who attended visits 5 and 6 and had late-onset epilepsy ascertainment available, they found that the relative risk ratio for dementia at visit 6 was 2.90 (95% CI, 1.22-6.92; P = .009). The RRR for MCI was 0.97 (95% CI, 0.39-2.38; P = .803). The greater functional impairment in patients with late-onset epilepsy may explain the lack of a relationship between late-onset epilepsy and MCI.

“It will be important for neurologists to be aware of the possibility of cognitive impairment following late-onset epilepsy and to check in with patients and family members to see if there are concerns,” said Dr. Johnson.

“We should also be talking about the importance of lowering other risk factors for dementia by making sure cardiovascular risk factors are controlled and encouraging physical and cognitive activity,” she added.

The results require confirmation in a clinical population, the investigators noted. In addition, future research is necessary to clarify whether seizures directly increase the risk of dementia or whether shared neuropathology between epilepsy and dementia explains the risk.

“In the near future, I plan to enroll participants with late-onset epilepsy in an observational study to better understand factors that may contribute to cognitive change. Collaborations will be key as we seek to further understand what causes these changes and what could be done to prevent them,” Dr. Johnson added.
 

Strengths and weaknesses

In an accompanying editorial, W. Allen Hauser, MD, professor emeritus of neurology and epidemiology at Columbia University in New York, and colleagues noted that the findings support a bidirectional relationship between dementia and epilepsy, adding that accumulation of amyloid beta peptide is a plausible underlying pathophysiology that may explain this relationship.

Future research should clarify the effect of factors such as seizure type, seizure frequency, and age of onset on the risk of dementia among patients with epilepsy, the editorialists wrote. Such investigations could help elucidate the underlying mechanisms of these conditions and help to improve treatment, they added.

Commenting on the findings, Ilo Leppik, MD, professor of neurology and pharmacy at the University of Minnesota in Minneapolis described the research as “a very well-done study by qualified researchers in the field. … For the last century, medicine has unfortunately become compartmentalized by specialty and then subspecialty. The brain and disorders of the brain do not recognize these silos. … It is not a stretch of the known science to begin to understand that epilepsy and dementia have common anatomical and physiological underpinnings.”

The long period of prospectively gathering data and the measurement of cognitive function through various modalities are among the study’s great strengths, said Dr. Leppik. However, the study’s weakness is its reliance on Medicare claims data, which mainly would reflect convulsive seizures.

“What is missing is how many persons had subtle focal-unaware seizures that may not be identified unless a careful history is taken,” said Dr. Leppik. “Thus, this study likely underestimates the frequency of epilepsy.”

Neurologists who evaluate a person with early dementia should be on the lookout for a history of subtle seizures, said Dr. Leppik. Animal studies suggest treatment with levetiracetam or brivaracetam may slow the course of dementia, and a clinical study in participants with early dementia is underway.

“Treatment with an antiseizure drug may prove to be beneficial, especially if evidence for the presence of subtle epilepsy can be found,” Dr. Leppik added.

Greater collaboration between epileptologists and dementia specialists and larger studies of antiseizure drugs are necessary, he noted. “These studies can incorporate sophisticated structural and biochemical [analyses] to better identify the relationships between brain mechanisms that likely underlie both seizures and dementia. The ultimate promise is that early treatment of seizures may alter the course of dementia,” Dr. Leppik said.

The study by Dr. Johnson and colleagues was supported by a contract from the National Institute on Aging; ARIC from the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. The authors and Dr. Leppik have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

For patients suspected of having a large-vessel occlusion stroke, direct transfer to a comprehensive stroke center capable of endovascular therapy that is farther away than a local primary stroke center does not necessarily produce better functional stroke outcomes, a new study has shown.

In the RACECAT trial, functional outcomes were similar for patients suspected of having a large-vessel occlusion stroke who were located in areas not currently served by a comprehensive stroke center, whether they were first taken to a local primary stroke center or whether they were transported over a longer distance to a comprehensive center.

“Under the particular conditions in our study where we had a very well-organized system, a ‘mothership’ transfer protocol for patients with suspected large-vessel occlusion has not proven superior over the ‘drip-and-ship’ protocol, but the opposite is also true,” lead investigator Marc Ribo, MD, concluded.

Dr. Ribo, assistant professor of neurology at Hospital Vall d’Hebron, Barcelona, presented the RACECAT results at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Dr. Ribo said in an interview that there is a feeling among the stroke community that patients with a suspected large-vessel occlusion should be transferred directly to a comprehensive stroke center capable of performing endovascular thrombectomy, even if there is a nearer, smaller primary stroke center where patients are usually taken first for thrombolysis.

“Many stroke neurologists believe we are losing time by sending patients with severe stroke to a local hospital and that we should skip this step, but this is controversial area,” he commented. “Our findings suggest that we should not automatically bypass local stroke centers.”

Dr. Ribo pointed out that the local centers performed very well in the study, with very fast “in/out” times for patients who were subsequently transferred for thrombectomy.

“On the basis of our results, we recommend that if a local stroke center can perform well like ours did – if they are within the time indicators for treating and transferring patients – then they should keep receiving these patients. But if they are not performing well in this regard, then they should probably be bypassed,” he commented.

The RACECAT trial was well received by stroke experts at an ESO-WSO 2020 press conference at which it was discussed.

Stefan Kiechl, MD, Medical University Innsbruck (Austria), described the trial as “outstanding,” adding: “It has addressed a very important question. It is a big achievement in stroke medicine.”

Patrik Michel, MD, Lausanne (Switzerland) University Hospital, said that “this is a very important and highly sophisticated trial in terms of design and execution. The message is that it doesn’t matter which pathway is used, but it is important to have a well-organized network with highly trained paramedics.”
 

RACECAT

The RACECAT trial was conducted in the Catalonia region of Spain. Twenty-seven hospitals participated, including 7 comprehensive stroke centers and 20 local stroke centers.

The trial included stroke patients with suspected large-vessel occlusion stroke, as determined on the basis of evaluation by paramedics using the criteria of a Rapid Arterial Occlusion Evaluation (RACE) scale score above 4 and on the basis of a call to a vascular neurologist. For inclusion in the study, patients had to be in a geographical area not served by a comprehensive stroke center and to have an estimated arrival time to a comprehensive center of less than 7 hours from symptom onset in order that thrombectomy would be possible.

Of 7,475 stroke code patients evaluated, 1,401 met the inclusion criteria and were randomly assigned to be transferred to a local hospital or to a comprehensive stroke center farther away.

Baseline characteristics were similar between the two groups. The patients had severe strokes with an average National Institutes of Health Stroke Scale score of 17. It was later confirmed that 46% of the patients enrolled in the study had a large-vessel occlusion stroke.

Results showed that time from symptom onset to hospital arrival was 142 minutes for those taken to a local center and 216 minutes for those taken to a comprehensive stroke center. Of those taken to a local hospital, 86% arrived within 4 hours of symptom onset and so were potential candidates for thrombolysis, compared with 76% of those taken to a comprehensive center.

Of the patients taken to a local hospital, 60% were given thrombolysis versus 43% of those taken immediately to a comprehensive center. On the other hand, 50% of patients who were taken directly to a comprehensive center underwent thrombectomy, compared with 40% who were first taken to a local center.

For patients who received thrombolysis, time to tissue plasminogen activator administration was 120 minutes for those treated at a local hospital versus 155 minutes for those taken directly to a comprehensive center.

For patients who received thrombectomy, time from symptom onset to groin puncture was 270 minutes if they were first taken to a local hospital and were then transferred, versus 214 minutes for those taken directly to the comprehensive center.

The primary efficacy endpoint was functional outcome using Modified Rankin Scale (mRS) shift analysis at 90 days for ischemic stroke patients. This showed a “completely flat” result, Dr. Ribo reported, with an adjusted hazard ratio of 1.029 for patients taken to a comprehensive center in comparison with those taken to a local center.

“There was absolutely no trend towards benefit in one group over the other,” he said.
 

What about hemorrhagic stroke?

The study also evaluated functional outcomes for the whole population enrolled. “If we make the decision just based on thrombectomy-eligible patients, we may harm the rest of the patients, so we did this study to look at the whole population of severe stroke patients,” Dr. Ribo said.

Of the study population, 25% of patients were found to have had a hemorrhagic stroke.

“The problem is, at the prehospital level, it is impossible to know if a patient is having a large-vessel occlusion ischemic stroke or a hemorrhagic stroke,” Dr. Ribo explained. “We have to make a decision for the whole population, and while a longer transport time to get to a comprehensive stroke center might help a patient with a large-vessel occlusion ischemic stroke, it might not be so appropriate for patients with a hemorrhagic stroke who need to have their blood pressure stabilized as soon as possible.”

For the whole population, the mRS shift analysis at 90 days was also neutral, with an aHR of 0.965.

When considering only patients with hemorrhagic stroke, the adjusted hazard ratio for the mRS shift analysis at 90 days was 1.216, which was still nonsignificant (95% confidence interval, 0.864-1.709). This included a nonsignificant increase in mortality among those taken directly to a comprehensive center.

“If we had better tools for a certain diagnosis in the field, then we could consider taking large-vessel occlusion ischemic stroke patients to a comprehensive center and hemorrhagic stroke patients to the local stroke center, but so far, we don’t have this option apart from a few places using mobile stroke units with CT scanners,” Dr. Ribo noted.

Transfer times to comprehensive centers in the study ranged from 30 minutes to 2.5 hours. “There might well be a difference in outcomes for short and long transfers, and we may be able to offer different transfer protocols in these different situations, and we are looking at that, but the study was only stopped in June, and we haven’t had a chance to analyze those results yet,” Dr. Ribo added.

Complications during transport occurred in 0.5% of those taken to a local hospital and in 1% of those taken directly to a comprehensive center. “We were concerned about complications with longer transfers, but these numbers are quite low. Intubations were very low – just one patient taken to a local center, versus three or four in the longer transfer group,” he added.

For both local and comprehensive centers, treatment times were impressive in the study. For local hospitals, the average in/out time was just 60 minutes for patients who went to a comprehensive center; for patients receiving thrombolysis, the average door to needle time was around 30 minutes.

Time to thrombectomy in the comprehensive center for patients transferred from a local hospital was also very fast, with an average door to groin puncture time of less than 40 minutes. “This shows we have a very well-oiled system,” Dr. Ribo said.

“There is always going to be a balance between a quicker time to thrombolysis by taking a patient to the closest hospital but a quicker time to thrombectomy if patients are taken straight to the comprehensive center,” he concluded. “But in our system, where we are achieving fast treatment and transfer times, our results show that patients had timely access to reperfusion therapies regardless of transfer protocol, and under these circumstances, it is fine for the emergency services to take stroke patients to the closest stroke center.”
 

Results applicable elsewhere?

During the discussion at an ESO-WSO 2020 press conference, other experts pointed out that the Catalonia group is a leader in this field, being the pioneers of the RACE score used in this study for paramedics to identify suspected large-vessel occlusions. This led to questions about the applicability of the results.

“The performance by paramedics was very good using the RACE scale, and the performance times were very impressive. Are these results applicable elsewhere?” Dr. Kiechl asked.

Dr. Ribo said the combination of the RACE score and a call with a vascular neurologist was of “great value” in identifying appropriate patients. Half of the patients selected in this way for the trial were confirmed to have a large-vessel occlusion. “That is a good result,” he added.

He noted that the performance of the local hospitals improved dramatically during the study. “They had an incentive to work on their times. They could have lost most of their stroke patients if their results came out worse. We told them they had an opportunity to show that they have a role in treating these patients, and they took that opportunity.”

Dr. Ribo said there were lessons here for those involved in acute stroke care. “When creating stroke transfer policies in local networks, the performances of individual centers need to be taken into account. If primary stroke centers are motivated and can work in a well-coordinated way and perform to within the recommended times, then they can keep receiving stroke code patients. This should be possible in most developed countries.”

Noting that the in/out time of 60 minutes at local hospitals was “very impressive,” Dr. Kiechl asked how such fast times were achieved.

Dr. Ribo responded that, to a great extent, this was because of ambulance staff. “We have trained the paramedics to anticipate a second transfer after delivering the patient to the local hospital so they can prepare for this rather than waiting for a second call.”

Dr. Ribo pointed out that there were other advantages in taking patients to local centers first. “For those that do not need to be transferred on, they will be closer to relatives. It is very difficult for the family if the patient is hundreds of miles away. And there may be a cost advantage. We did look at costs, but haven’t got that data yet.”

He said: “If local stroke centers do not treat so many stroke code patients, they will lose their expertise, and that will be detrimental to the remaining patients who are taken there. We want to try to maintain a good standard of stroke care across a decent spread of hospitals—not just a couple of major comprehensive centers,” he added.

Commenting on the study, Jesse Dawson, MD, University of Glasgow, who was chair of the plenary session at which the study was presented, said: “RACECAT is very interesting but needs a lot of thought to dissect. My takeaway is that we know that time to reperfusion is key, and we need to get these times as low as possible, but we don’t need to chase a particular care pathway. Thus, if your country/geography suits ‘drip and ship’ better, this is acceptable. If direct to endovascular is possible or you are close to such a center, then this is ideal. But within those paradigms, be as fast as possible.”

He added that results of the subgroups with regard to transfer time will be helpful.

The RACECAT study was funded by Fundacio Ictus Malaltia Vascular.

A version of this article originally appeared on Medscape.com.

For patients suspected of having a large-vessel occlusion stroke, direct transfer to a comprehensive stroke center capable of endovascular therapy that is farther away than a local primary stroke center does not necessarily produce better functional stroke outcomes, a new study has shown.

In the RACECAT trial, functional outcomes were similar for patients suspected of having a large-vessel occlusion stroke who were located in areas not currently served by a comprehensive stroke center, whether they were first taken to a local primary stroke center or whether they were transported over a longer distance to a comprehensive center.

“Under the particular conditions in our study where we had a very well-organized system, a ‘mothership’ transfer protocol for patients with suspected large-vessel occlusion has not proven superior over the ‘drip-and-ship’ protocol, but the opposite is also true,” lead investigator Marc Ribo, MD, concluded.

Dr. Ribo, assistant professor of neurology at Hospital Vall d’Hebron, Barcelona, presented the RACECAT results at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Dr. Ribo said in an interview that there is a feeling among the stroke community that patients with a suspected large-vessel occlusion should be transferred directly to a comprehensive stroke center capable of performing endovascular thrombectomy, even if there is a nearer, smaller primary stroke center where patients are usually taken first for thrombolysis.

“Many stroke neurologists believe we are losing time by sending patients with severe stroke to a local hospital and that we should skip this step, but this is controversial area,” he commented. “Our findings suggest that we should not automatically bypass local stroke centers.”

Dr. Ribo pointed out that the local centers performed very well in the study, with very fast “in/out” times for patients who were subsequently transferred for thrombectomy.

“On the basis of our results, we recommend that if a local stroke center can perform well like ours did – if they are within the time indicators for treating and transferring patients – then they should keep receiving these patients. But if they are not performing well in this regard, then they should probably be bypassed,” he commented.

The RACECAT trial was well received by stroke experts at an ESO-WSO 2020 press conference at which it was discussed.

Stefan Kiechl, MD, Medical University Innsbruck (Austria), described the trial as “outstanding,” adding: “It has addressed a very important question. It is a big achievement in stroke medicine.”

Patrik Michel, MD, Lausanne (Switzerland) University Hospital, said that “this is a very important and highly sophisticated trial in terms of design and execution. The message is that it doesn’t matter which pathway is used, but it is important to have a well-organized network with highly trained paramedics.”
 

RACECAT

The RACECAT trial was conducted in the Catalonia region of Spain. Twenty-seven hospitals participated, including 7 comprehensive stroke centers and 20 local stroke centers.

The trial included stroke patients with suspected large-vessel occlusion stroke, as determined on the basis of evaluation by paramedics using the criteria of a Rapid Arterial Occlusion Evaluation (RACE) scale score above 4 and on the basis of a call to a vascular neurologist. For inclusion in the study, patients had to be in a geographical area not served by a comprehensive stroke center and to have an estimated arrival time to a comprehensive center of less than 7 hours from symptom onset in order that thrombectomy would be possible.

Of 7,475 stroke code patients evaluated, 1,401 met the inclusion criteria and were randomly assigned to be transferred to a local hospital or to a comprehensive stroke center farther away.

Baseline characteristics were similar between the two groups. The patients had severe strokes with an average National Institutes of Health Stroke Scale score of 17. It was later confirmed that 46% of the patients enrolled in the study had a large-vessel occlusion stroke.

Results showed that time from symptom onset to hospital arrival was 142 minutes for those taken to a local center and 216 minutes for those taken to a comprehensive stroke center. Of those taken to a local hospital, 86% arrived within 4 hours of symptom onset and so were potential candidates for thrombolysis, compared with 76% of those taken to a comprehensive center.

Of the patients taken to a local hospital, 60% were given thrombolysis versus 43% of those taken immediately to a comprehensive center. On the other hand, 50% of patients who were taken directly to a comprehensive center underwent thrombectomy, compared with 40% who were first taken to a local center.

For patients who received thrombolysis, time to tissue plasminogen activator administration was 120 minutes for those treated at a local hospital versus 155 minutes for those taken directly to a comprehensive center.

For patients who received thrombectomy, time from symptom onset to groin puncture was 270 minutes if they were first taken to a local hospital and were then transferred, versus 214 minutes for those taken directly to the comprehensive center.

The primary efficacy endpoint was functional outcome using Modified Rankin Scale (mRS) shift analysis at 90 days for ischemic stroke patients. This showed a “completely flat” result, Dr. Ribo reported, with an adjusted hazard ratio of 1.029 for patients taken to a comprehensive center in comparison with those taken to a local center.

“There was absolutely no trend towards benefit in one group over the other,” he said.
 

What about hemorrhagic stroke?

The study also evaluated functional outcomes for the whole population enrolled. “If we make the decision just based on thrombectomy-eligible patients, we may harm the rest of the patients, so we did this study to look at the whole population of severe stroke patients,” Dr. Ribo said.

Of the study population, 25% of patients were found to have had a hemorrhagic stroke.

“The problem is, at the prehospital level, it is impossible to know if a patient is having a large-vessel occlusion ischemic stroke or a hemorrhagic stroke,” Dr. Ribo explained. “We have to make a decision for the whole population, and while a longer transport time to get to a comprehensive stroke center might help a patient with a large-vessel occlusion ischemic stroke, it might not be so appropriate for patients with a hemorrhagic stroke who need to have their blood pressure stabilized as soon as possible.”

For the whole population, the mRS shift analysis at 90 days was also neutral, with an aHR of 0.965.

When considering only patients with hemorrhagic stroke, the adjusted hazard ratio for the mRS shift analysis at 90 days was 1.216, which was still nonsignificant (95% confidence interval, 0.864-1.709). This included a nonsignificant increase in mortality among those taken directly to a comprehensive center.

“If we had better tools for a certain diagnosis in the field, then we could consider taking large-vessel occlusion ischemic stroke patients to a comprehensive center and hemorrhagic stroke patients to the local stroke center, but so far, we don’t have this option apart from a few places using mobile stroke units with CT scanners,” Dr. Ribo noted.

Transfer times to comprehensive centers in the study ranged from 30 minutes to 2.5 hours. “There might well be a difference in outcomes for short and long transfers, and we may be able to offer different transfer protocols in these different situations, and we are looking at that, but the study was only stopped in June, and we haven’t had a chance to analyze those results yet,” Dr. Ribo added.

Complications during transport occurred in 0.5% of those taken to a local hospital and in 1% of those taken directly to a comprehensive center. “We were concerned about complications with longer transfers, but these numbers are quite low. Intubations were very low – just one patient taken to a local center, versus three or four in the longer transfer group,” he added.

For both local and comprehensive centers, treatment times were impressive in the study. For local hospitals, the average in/out time was just 60 minutes for patients who went to a comprehensive center; for patients receiving thrombolysis, the average door to needle time was around 30 minutes.

Time to thrombectomy in the comprehensive center for patients transferred from a local hospital was also very fast, with an average door to groin puncture time of less than 40 minutes. “This shows we have a very well-oiled system,” Dr. Ribo said.

“There is always going to be a balance between a quicker time to thrombolysis by taking a patient to the closest hospital but a quicker time to thrombectomy if patients are taken straight to the comprehensive center,” he concluded. “But in our system, where we are achieving fast treatment and transfer times, our results show that patients had timely access to reperfusion therapies regardless of transfer protocol, and under these circumstances, it is fine for the emergency services to take stroke patients to the closest stroke center.”
 

Results applicable elsewhere?

During the discussion at an ESO-WSO 2020 press conference, other experts pointed out that the Catalonia group is a leader in this field, being the pioneers of the RACE score used in this study for paramedics to identify suspected large-vessel occlusions. This led to questions about the applicability of the results.

“The performance by paramedics was very good using the RACE scale, and the performance times were very impressive. Are these results applicable elsewhere?” Dr. Kiechl asked.

Dr. Ribo said the combination of the RACE score and a call with a vascular neurologist was of “great value” in identifying appropriate patients. Half of the patients selected in this way for the trial were confirmed to have a large-vessel occlusion. “That is a good result,” he added.

He noted that the performance of the local hospitals improved dramatically during the study. “They had an incentive to work on their times. They could have lost most of their stroke patients if their results came out worse. We told them they had an opportunity to show that they have a role in treating these patients, and they took that opportunity.”

Dr. Ribo said there were lessons here for those involved in acute stroke care. “When creating stroke transfer policies in local networks, the performances of individual centers need to be taken into account. If primary stroke centers are motivated and can work in a well-coordinated way and perform to within the recommended times, then they can keep receiving stroke code patients. This should be possible in most developed countries.”

Noting that the in/out time of 60 minutes at local hospitals was “very impressive,” Dr. Kiechl asked how such fast times were achieved.

Dr. Ribo responded that, to a great extent, this was because of ambulance staff. “We have trained the paramedics to anticipate a second transfer after delivering the patient to the local hospital so they can prepare for this rather than waiting for a second call.”

Dr. Ribo pointed out that there were other advantages in taking patients to local centers first. “For those that do not need to be transferred on, they will be closer to relatives. It is very difficult for the family if the patient is hundreds of miles away. And there may be a cost advantage. We did look at costs, but haven’t got that data yet.”

He said: “If local stroke centers do not treat so many stroke code patients, they will lose their expertise, and that will be detrimental to the remaining patients who are taken there. We want to try to maintain a good standard of stroke care across a decent spread of hospitals—not just a couple of major comprehensive centers,” he added.

Commenting on the study, Jesse Dawson, MD, University of Glasgow, who was chair of the plenary session at which the study was presented, said: “RACECAT is very interesting but needs a lot of thought to dissect. My takeaway is that we know that time to reperfusion is key, and we need to get these times as low as possible, but we don’t need to chase a particular care pathway. Thus, if your country/geography suits ‘drip and ship’ better, this is acceptable. If direct to endovascular is possible or you are close to such a center, then this is ideal. But within those paradigms, be as fast as possible.”

He added that results of the subgroups with regard to transfer time will be helpful.

The RACECAT study was funded by Fundacio Ictus Malaltia Vascular.

A version of this article originally appeared on Medscape.com.

For patients suspected of having a large-vessel occlusion stroke, direct transfer to a comprehensive stroke center capable of endovascular therapy that is farther away than a local primary stroke center does not necessarily produce better functional stroke outcomes, a new study has shown.

In the RACECAT trial, functional outcomes were similar for patients suspected of having a large-vessel occlusion stroke who were located in areas not currently served by a comprehensive stroke center, whether they were first taken to a local primary stroke center or whether they were transported over a longer distance to a comprehensive center.

“Under the particular conditions in our study where we had a very well-organized system, a ‘mothership’ transfer protocol for patients with suspected large-vessel occlusion has not proven superior over the ‘drip-and-ship’ protocol, but the opposite is also true,” lead investigator Marc Ribo, MD, concluded.

Dr. Ribo, assistant professor of neurology at Hospital Vall d’Hebron, Barcelona, presented the RACECAT results at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Dr. Ribo said in an interview that there is a feeling among the stroke community that patients with a suspected large-vessel occlusion should be transferred directly to a comprehensive stroke center capable of performing endovascular thrombectomy, even if there is a nearer, smaller primary stroke center where patients are usually taken first for thrombolysis.

“Many stroke neurologists believe we are losing time by sending patients with severe stroke to a local hospital and that we should skip this step, but this is controversial area,” he commented. “Our findings suggest that we should not automatically bypass local stroke centers.”

Dr. Ribo pointed out that the local centers performed very well in the study, with very fast “in/out” times for patients who were subsequently transferred for thrombectomy.

“On the basis of our results, we recommend that if a local stroke center can perform well like ours did – if they are within the time indicators for treating and transferring patients – then they should keep receiving these patients. But if they are not performing well in this regard, then they should probably be bypassed,” he commented.

The RACECAT trial was well received by stroke experts at an ESO-WSO 2020 press conference at which it was discussed.

Stefan Kiechl, MD, Medical University Innsbruck (Austria), described the trial as “outstanding,” adding: “It has addressed a very important question. It is a big achievement in stroke medicine.”

Patrik Michel, MD, Lausanne (Switzerland) University Hospital, said that “this is a very important and highly sophisticated trial in terms of design and execution. The message is that it doesn’t matter which pathway is used, but it is important to have a well-organized network with highly trained paramedics.”
 

RACECAT

The RACECAT trial was conducted in the Catalonia region of Spain. Twenty-seven hospitals participated, including 7 comprehensive stroke centers and 20 local stroke centers.

The trial included stroke patients with suspected large-vessel occlusion stroke, as determined on the basis of evaluation by paramedics using the criteria of a Rapid Arterial Occlusion Evaluation (RACE) scale score above 4 and on the basis of a call to a vascular neurologist. For inclusion in the study, patients had to be in a geographical area not served by a comprehensive stroke center and to have an estimated arrival time to a comprehensive center of less than 7 hours from symptom onset in order that thrombectomy would be possible.

Of 7,475 stroke code patients evaluated, 1,401 met the inclusion criteria and were randomly assigned to be transferred to a local hospital or to a comprehensive stroke center farther away.

Baseline characteristics were similar between the two groups. The patients had severe strokes with an average National Institutes of Health Stroke Scale score of 17. It was later confirmed that 46% of the patients enrolled in the study had a large-vessel occlusion stroke.

Results showed that time from symptom onset to hospital arrival was 142 minutes for those taken to a local center and 216 minutes for those taken to a comprehensive stroke center. Of those taken to a local hospital, 86% arrived within 4 hours of symptom onset and so were potential candidates for thrombolysis, compared with 76% of those taken to a comprehensive center.

Of the patients taken to a local hospital, 60% were given thrombolysis versus 43% of those taken immediately to a comprehensive center. On the other hand, 50% of patients who were taken directly to a comprehensive center underwent thrombectomy, compared with 40% who were first taken to a local center.

For patients who received thrombolysis, time to tissue plasminogen activator administration was 120 minutes for those treated at a local hospital versus 155 minutes for those taken directly to a comprehensive center.

For patients who received thrombectomy, time from symptom onset to groin puncture was 270 minutes if they were first taken to a local hospital and were then transferred, versus 214 minutes for those taken directly to the comprehensive center.

The primary efficacy endpoint was functional outcome using Modified Rankin Scale (mRS) shift analysis at 90 days for ischemic stroke patients. This showed a “completely flat” result, Dr. Ribo reported, with an adjusted hazard ratio of 1.029 for patients taken to a comprehensive center in comparison with those taken to a local center.

“There was absolutely no trend towards benefit in one group over the other,” he said.
 

What about hemorrhagic stroke?

The study also evaluated functional outcomes for the whole population enrolled. “If we make the decision just based on thrombectomy-eligible patients, we may harm the rest of the patients, so we did this study to look at the whole population of severe stroke patients,” Dr. Ribo said.

Of the study population, 25% of patients were found to have had a hemorrhagic stroke.

“The problem is, at the prehospital level, it is impossible to know if a patient is having a large-vessel occlusion ischemic stroke or a hemorrhagic stroke,” Dr. Ribo explained. “We have to make a decision for the whole population, and while a longer transport time to get to a comprehensive stroke center might help a patient with a large-vessel occlusion ischemic stroke, it might not be so appropriate for patients with a hemorrhagic stroke who need to have their blood pressure stabilized as soon as possible.”

For the whole population, the mRS shift analysis at 90 days was also neutral, with an aHR of 0.965.

When considering only patients with hemorrhagic stroke, the adjusted hazard ratio for the mRS shift analysis at 90 days was 1.216, which was still nonsignificant (95% confidence interval, 0.864-1.709). This included a nonsignificant increase in mortality among those taken directly to a comprehensive center.

“If we had better tools for a certain diagnosis in the field, then we could consider taking large-vessel occlusion ischemic stroke patients to a comprehensive center and hemorrhagic stroke patients to the local stroke center, but so far, we don’t have this option apart from a few places using mobile stroke units with CT scanners,” Dr. Ribo noted.

Transfer times to comprehensive centers in the study ranged from 30 minutes to 2.5 hours. “There might well be a difference in outcomes for short and long transfers, and we may be able to offer different transfer protocols in these different situations, and we are looking at that, but the study was only stopped in June, and we haven’t had a chance to analyze those results yet,” Dr. Ribo added.

Complications during transport occurred in 0.5% of those taken to a local hospital and in 1% of those taken directly to a comprehensive center. “We were concerned about complications with longer transfers, but these numbers are quite low. Intubations were very low – just one patient taken to a local center, versus three or four in the longer transfer group,” he added.

For both local and comprehensive centers, treatment times were impressive in the study. For local hospitals, the average in/out time was just 60 minutes for patients who went to a comprehensive center; for patients receiving thrombolysis, the average door to needle time was around 30 minutes.

Time to thrombectomy in the comprehensive center for patients transferred from a local hospital was also very fast, with an average door to groin puncture time of less than 40 minutes. “This shows we have a very well-oiled system,” Dr. Ribo said.

“There is always going to be a balance between a quicker time to thrombolysis by taking a patient to the closest hospital but a quicker time to thrombectomy if patients are taken straight to the comprehensive center,” he concluded. “But in our system, where we are achieving fast treatment and transfer times, our results show that patients had timely access to reperfusion therapies regardless of transfer protocol, and under these circumstances, it is fine for the emergency services to take stroke patients to the closest stroke center.”
 

Results applicable elsewhere?

During the discussion at an ESO-WSO 2020 press conference, other experts pointed out that the Catalonia group is a leader in this field, being the pioneers of the RACE score used in this study for paramedics to identify suspected large-vessel occlusions. This led to questions about the applicability of the results.

“The performance by paramedics was very good using the RACE scale, and the performance times were very impressive. Are these results applicable elsewhere?” Dr. Kiechl asked.

Dr. Ribo said the combination of the RACE score and a call with a vascular neurologist was of “great value” in identifying appropriate patients. Half of the patients selected in this way for the trial were confirmed to have a large-vessel occlusion. “That is a good result,” he added.

He noted that the performance of the local hospitals improved dramatically during the study. “They had an incentive to work on their times. They could have lost most of their stroke patients if their results came out worse. We told them they had an opportunity to show that they have a role in treating these patients, and they took that opportunity.”

Dr. Ribo said there were lessons here for those involved in acute stroke care. “When creating stroke transfer policies in local networks, the performances of individual centers need to be taken into account. If primary stroke centers are motivated and can work in a well-coordinated way and perform to within the recommended times, then they can keep receiving stroke code patients. This should be possible in most developed countries.”

Noting that the in/out time of 60 minutes at local hospitals was “very impressive,” Dr. Kiechl asked how such fast times were achieved.

Dr. Ribo responded that, to a great extent, this was because of ambulance staff. “We have trained the paramedics to anticipate a second transfer after delivering the patient to the local hospital so they can prepare for this rather than waiting for a second call.”

Dr. Ribo pointed out that there were other advantages in taking patients to local centers first. “For those that do not need to be transferred on, they will be closer to relatives. It is very difficult for the family if the patient is hundreds of miles away. And there may be a cost advantage. We did look at costs, but haven’t got that data yet.”

He said: “If local stroke centers do not treat so many stroke code patients, they will lose their expertise, and that will be detrimental to the remaining patients who are taken there. We want to try to maintain a good standard of stroke care across a decent spread of hospitals—not just a couple of major comprehensive centers,” he added.

Commenting on the study, Jesse Dawson, MD, University of Glasgow, who was chair of the plenary session at which the study was presented, said: “RACECAT is very interesting but needs a lot of thought to dissect. My takeaway is that we know that time to reperfusion is key, and we need to get these times as low as possible, but we don’t need to chase a particular care pathway. Thus, if your country/geography suits ‘drip and ship’ better, this is acceptable. If direct to endovascular is possible or you are close to such a center, then this is ideal. But within those paradigms, be as fast as possible.”

He added that results of the subgroups with regard to transfer time will be helpful.

The RACECAT study was funded by Fundacio Ictus Malaltia Vascular.

A version of this article originally appeared on Medscape.com.

When Steven Horowitz, MD, began experiencing neck and arm pain, numbness, and tingling following a bike ride several years ago, he immediately sought care at an elite medical center in California. As he recalls, an incompetent clinical exam and no access to highly abnormal test results done in the ED almost cost him his health. Had he listened to the doctors at that facility, he believes he would have become quadriplegic.

His training as a neurologist likely saved his life: “I was able to recover because, after arriving home, I reviewed my blood work and MRI online and recognized multiple problems.” He was able to get excellent care at his own local health care facility in Maine. The staff and leadership at the hospital in California wouldn’t admit wrongdoing, and efforts to seek recourse have proved fruitless, he said.

A lingering question nags at him: What if he had been an ordinary patient without medical expertise? What do his experiences say about the health care system’s management of medical omissions and errors?

Dr. Horowitz, 78 years old and retired, continues to teach medical students as an adjunct clinical professor of neurology at the Tufts University School of Medicine in Boston. He is also on the teaching faculty of the Maine Medical Center. He was professor and chief of neurology at a major university in the Midwest for many years.

In 2018, he visited his daughter on the West Coast, enjoying a day of biking. The neck pain began 5 or 6 hours after the ride and spread to his arms. “There was also numbness and tingling,” he said.
 

“I told them I was a neurologist”

The next day the pain got worse. Dr. Horowitz went to the ED of a nearby medical center with his daughter and immediately disclosed that he was a neurologist. “I did this for several reasons,” he explained. He wanted to alert staff that he had a cervical spine problem because “I wanted them to do a cervical MRI scan, and I wanted to read it because I’m capable of doing that.” He also related a past history of infection and antibiotic use and asked for C-reactive protein and erythrocyte sedimentation rate tests in addition to regular blood work. “Those inflammatory markers, if abnormal, would indicate an infection,” said Dr. Horowitz.

No reflex hammer or Babinski test

During the reflex exam with a spine consultant, Dr. Horowitz noticed that the consultant wasn’t using a reflex hammer, the clinical equivalent of evaluating the heart or lungs without a stethoscope. “I asked where the reflex hammer was, and he said he didn’t need one or own one. He used the inside of his hand. Apparently, there was some mild weakness in some muscle groups, but he didn’t address that,” said Dr. Horowitz. The consultant also didn’t test for the Babinski sign until reminded of it.

He took out a stethoscope and struck the middle of the soles of Dr. Horowitz’s feet. “I thought to myself, this consultant is the consultant for the spine service? How is it possible that he has a stethoscope and not a reflex hammer and didn’t know how to test for the Babinski sign?” The consultant also didn’t examine for gait, coordination, or hand dexterity. “He took his finger and touched my feet and legs. That was his sensory exam. He didn’t use a pin or a tuning fork” or other methods including touch, temperature, position sense, and vibration to assess sensory abnormalities that might signal spinal cord dysfunction.

An MRI at the hospital revealed a mass at the back of the neck. No contrast material was used during the MRI even though this step would have signaled the presence of infection. “Gadolinium should have been injected during the MRI because that would have strongly suggested that this mass in my neck was not a little blood clot and more likely an infection. They would have realized something more complicated than degenerative arthritis was going on. They told me that I had advanced spondylosis and that the mass was a hematoma. They told me not to worry about the blood results. Then they discharged me.”
 

A life-threatening discovery

Dr. Horowitz didn’t see the results of the blood work-up until returning to Maine a few days later, when he checked the online report. There was a highly elevated CRP level – 30 times above the normal limit – and elevated erythrocyte sedimentation rate and white blood cell counts. “This showed that there was an infective process going on. And it wasn’t just a localized process, it was in my bloodstream,” he said.

Alarmed by the elevated markers, he immediately went to his local hospital. “Not only did I have arthritis, but my spinal cord was compressed.” Urgent surgery was performed, including a C2-7 fusion. The mass in the back of his neck turned out to be an abscess.

His training and experience as a physician/neurologist saved him from further damage, he said. “Because the compression of the spine was at the C2, C3, C4 level, not only would I have become quadriplegic, but my diaphragm would likely have been paralyzed and I would have needed a ventilator.”

Following a month’s care in the hospital and a rehabilitation center, he wrote to the CEO of the California hospital where he received his initial care.

“I wrote about the incompetent exam, the missed infection, a discharge without information. I wrote all that out to the CEO and sent the letter registered so that he would receive it.” The CEO forwarded the letter to a patient risk manager, who interviewed staff and supervisors in the ED, radiology, and the spine program. They responded 3 months later. According to Dr. Horowitz, the spine supervisor said, “The consultant performed the exam to the best of his ability.” No one admitted to any errors in care or the lack of recognition of the infection, although the neuroradiologist did apologize for not allowing Dr. Horowitz to read his own MRI in a timely manner.

“They had promised to wheel a portable computer into my alcove so I could view the MRI.” Several hours later, after persistent complaints, he was given 1 minute to look over at least 300 images at a desktop computer in the crowded ED. They gave him the MRI images on a disk, but he wasn’t able to read it on his iMac computer.

According to Dr. Horowitz, the ED should have called in an infectious disease consultant and a neurologist or neurosurgeon to do a more complete neurologic exam. “Instead of discharging me, they should have admitted me, telling me that I had spinal cord compression, an infection, and a mass in my neck—that they don’t know what this is about, and I shouldn’t go home.”

Eventually, after long-term intravenous antibiotics and extensive physical therapy, Dr. Horowitz recovered. “I definitely had PTSD afterwards. How could a non-eventful bike ride result in an unrecognized threatening illness? I thought a healing opportunity for me and an educational opportunity for the medical staff and students at this medical center would be for me to present my case to them at a conference at their facility the next time I visited my daughter in California. I thought an experienced clinician discussing his own illness in his own specialty would be unique.”

The hospital ignored his offer.

By happenstance, a year and a half later, Dr. Horowitz made contact with a hospital administrator after hearing her speak during a TED Radio Hour in his car. “We had several telephone conversations and email correspondences in October and November 2019 but none since,” he said. In one email, she wrote that “hospitals don’t seem to know what to do with the opportunity you present. I don’t think the challenge is unique to [this institution]. A forum for these kinds of discussions – constructive, insightful patient feedback – does not exist.”

Dr. Horowitz hasn’t considered a malpractice lawsuit. “The only result would be a monetary reward based on damages. Since permanent clinical damage did not occur, the suit would have been time consuming and the reward limited. I was able to recover because I was able to review the blood work and recognize my own problem and get excellent care at my own local health care facility. I was really hoping the doctors at the California hospital would learn from this episode.”

Dr. Horowitz also wrote the Medical Board of California a detailed letter, citing relevant medical literature, guidelines on spinal care, and his test results. Nearly 2 years later, he finally got a response. The board said there was no “clear and convincing evidence that negligence took place.” In Dr. Horowitz’s opinion, “the fact that CRP was 30 times past normal is ‘clear and convincing evidence.’ That the consultant didn’t have a reflex hammer is also ‘clear and convincing evidence.’ That the clinical neurologic exam was incompetent, by any measure, is ‘clear and convincing evidence.’ Even the Medical Board, tasked with patient protection, didn’t recognize negligent medical care. They might have if I had become quadriplegic.”
 

A new normal?

Dr. Horowitz, who wrote of his experience in The Washington Post, said it reflects a persistent, systemic problem in health care: the inability to address medical errors and correct them. In the article, he addressed a phenomenon called the “the normalization of deviance.” Diane Vaughn wrote about this phenomenon in a 1997 book about the Space Shuttle disaster. Multiple flaws were noted in previous shuttle launches but then rationalized and “normalized” when they didn’t cause a disaster – until they ultimately did.

“That’s relevant to my situation,” Dr. Horowitz said. “The spine supervisor at this hospital excused the consultant by saying, ‘he did the exam to the best of his ability.’ Further, the response to my complaints came from hospital representatives rather than physicians, meaning that the ‘normalization’ was institutional, and it was willing to accept his poor performance without sanctions.”

He imagines that he could not be the only case handled poorly by this hospital or that particular consultant. “He could have done the same thing to another patient who didn’t have my medical knowledge,” added Dr. Horowitz.

In her book, Ms. Vaughan noted that whistleblower activity is sometimes the only device that reveals normalization of deviance.

Dr. Horowitz sees himself as a whistleblower for these types of mistakes. “The question is, how do we deal with medical errors even in sophisticated patients who see these errors, and how do you manage this in the average patient? I don’t want to see this type of medical care rendered for any patient, hence my attempt to make this situation public.”
 

A teachable moment lost?

Commenting on this case, Alan Rapoport, MD, said, “[it]illustrates inadequate physician evaluation in the ED, poor communication from the examining doctor about abnormal lab and MRI findings, unwillingness to call in consultants to properly evaluate the situation, and no recognition of the need to admit the patient.”

Dr. Rapoport is the editor in chief of Neurology Reviews and a clinical professor of neurology at UCLA in Los Angeles. He is a past president of the International Headache Society.

He noted that the patient is in his late 70s and needed to fly across the country to arrive at home. “Months later, when this situation was explained to the hospital via the mail, they totally failed to recognize their inadequacies and apologize for their mistakes. They were probably concerned about being sued, but I believe that their actions increased their chances of a lawsuit,” Dr. Rapoport said.

“When a teaching remedy was offered by the patient to the hospital so the doctors involved could learn from the experience, the hospital was not interested. The only party that learned from this unfortunate episode was the patient, not the doctors, or the ER, or the hospital administration,” Dr. Rapoport said.

He continued, “It is scary to think that an excellent hospital would act in this manner and refuse to learn from their mistakes. The California medical board was notified and did not investigate. It is not too late for the hospital to apologize, communicate their shortcomings, and fix the problem at multiple levels in the hospital.”

Dr. Rapoport consulted Morris Levin, MD, a professor of neurology and director of the Headache Program at UCSF, to ask what he thought, theoretically, about how a hospital should respond when they make a mistake and how much they should divulge. Dr. Levin is involved in Medical Ethics and often lectures about it at conferences.

Dr. Levin said, “When medical errors are made, to me, it is ethically sound to identify them and ‘fess up.’ There has always been reluctance to do so because of fears of lawsuits, but it turns out that when institutions do disclose errors, their liability costs actually go down.” Dr. Levin cited the University of Michigan, which tried a full disclosure policy as an experiment. “It led to reduced costs, not to mention a boost in patient satisfaction,” Dr. Levin noted.

He continued, “I think patients want and deserve to know the truth. I also believe they understand that medical errors can and will happen. It is my observation that patients have several key concerns: 1) how the error(s) happened, 2) how the error affected their health and what can be done to restore them to optimal health, and 3) what the institution is going to do to prevent this kind of error from happening to others.”

Dr. Rapoport concurs with Dr. Levin. “I am glad Dr. Horowitz has fully recovered and at least he has learned from the experience. I do not think the hospital and doctors did,” Dr. Rapoport said.

This article was updated 11/12/20.

When Steven Horowitz, MD, began experiencing neck and arm pain, numbness, and tingling following a bike ride several years ago, he immediately sought care at an elite medical center in California. As he recalls, an incompetent clinical exam and no access to highly abnormal test results done in the ED almost cost him his health. Had he listened to the doctors at that facility, he believes he would have become quadriplegic.

His training as a neurologist likely saved his life: “I was able to recover because, after arriving home, I reviewed my blood work and MRI online and recognized multiple problems.” He was able to get excellent care at his own local health care facility in Maine. The staff and leadership at the hospital in California wouldn’t admit wrongdoing, and efforts to seek recourse have proved fruitless, he said.

A lingering question nags at him: What if he had been an ordinary patient without medical expertise? What do his experiences say about the health care system’s management of medical omissions and errors?

Dr. Horowitz, 78 years old and retired, continues to teach medical students as an adjunct clinical professor of neurology at the Tufts University School of Medicine in Boston. He is also on the teaching faculty of the Maine Medical Center. He was professor and chief of neurology at a major university in the Midwest for many years.

In 2018, he visited his daughter on the West Coast, enjoying a day of biking. The neck pain began 5 or 6 hours after the ride and spread to his arms. “There was also numbness and tingling,” he said.
 

“I told them I was a neurologist”

The next day the pain got worse. Dr. Horowitz went to the ED of a nearby medical center with his daughter and immediately disclosed that he was a neurologist. “I did this for several reasons,” he explained. He wanted to alert staff that he had a cervical spine problem because “I wanted them to do a cervical MRI scan, and I wanted to read it because I’m capable of doing that.” He also related a past history of infection and antibiotic use and asked for C-reactive protein and erythrocyte sedimentation rate tests in addition to regular blood work. “Those inflammatory markers, if abnormal, would indicate an infection,” said Dr. Horowitz.

No reflex hammer or Babinski test

During the reflex exam with a spine consultant, Dr. Horowitz noticed that the consultant wasn’t using a reflex hammer, the clinical equivalent of evaluating the heart or lungs without a stethoscope. “I asked where the reflex hammer was, and he said he didn’t need one or own one. He used the inside of his hand. Apparently, there was some mild weakness in some muscle groups, but he didn’t address that,” said Dr. Horowitz. The consultant also didn’t test for the Babinski sign until reminded of it.

He took out a stethoscope and struck the middle of the soles of Dr. Horowitz’s feet. “I thought to myself, this consultant is the consultant for the spine service? How is it possible that he has a stethoscope and not a reflex hammer and didn’t know how to test for the Babinski sign?” The consultant also didn’t examine for gait, coordination, or hand dexterity. “He took his finger and touched my feet and legs. That was his sensory exam. He didn’t use a pin or a tuning fork” or other methods including touch, temperature, position sense, and vibration to assess sensory abnormalities that might signal spinal cord dysfunction.

An MRI at the hospital revealed a mass at the back of the neck. No contrast material was used during the MRI even though this step would have signaled the presence of infection. “Gadolinium should have been injected during the MRI because that would have strongly suggested that this mass in my neck was not a little blood clot and more likely an infection. They would have realized something more complicated than degenerative arthritis was going on. They told me that I had advanced spondylosis and that the mass was a hematoma. They told me not to worry about the blood results. Then they discharged me.”
 

A life-threatening discovery

Dr. Horowitz didn’t see the results of the blood work-up until returning to Maine a few days later, when he checked the online report. There was a highly elevated CRP level – 30 times above the normal limit – and elevated erythrocyte sedimentation rate and white blood cell counts. “This showed that there was an infective process going on. And it wasn’t just a localized process, it was in my bloodstream,” he said.

Alarmed by the elevated markers, he immediately went to his local hospital. “Not only did I have arthritis, but my spinal cord was compressed.” Urgent surgery was performed, including a C2-7 fusion. The mass in the back of his neck turned out to be an abscess.

His training and experience as a physician/neurologist saved him from further damage, he said. “Because the compression of the spine was at the C2, C3, C4 level, not only would I have become quadriplegic, but my diaphragm would likely have been paralyzed and I would have needed a ventilator.”

Following a month’s care in the hospital and a rehabilitation center, he wrote to the CEO of the California hospital where he received his initial care.

“I wrote about the incompetent exam, the missed infection, a discharge without information. I wrote all that out to the CEO and sent the letter registered so that he would receive it.” The CEO forwarded the letter to a patient risk manager, who interviewed staff and supervisors in the ED, radiology, and the spine program. They responded 3 months later. According to Dr. Horowitz, the spine supervisor said, “The consultant performed the exam to the best of his ability.” No one admitted to any errors in care or the lack of recognition of the infection, although the neuroradiologist did apologize for not allowing Dr. Horowitz to read his own MRI in a timely manner.

“They had promised to wheel a portable computer into my alcove so I could view the MRI.” Several hours later, after persistent complaints, he was given 1 minute to look over at least 300 images at a desktop computer in the crowded ED. They gave him the MRI images on a disk, but he wasn’t able to read it on his iMac computer.

According to Dr. Horowitz, the ED should have called in an infectious disease consultant and a neurologist or neurosurgeon to do a more complete neurologic exam. “Instead of discharging me, they should have admitted me, telling me that I had spinal cord compression, an infection, and a mass in my neck—that they don’t know what this is about, and I shouldn’t go home.”

Eventually, after long-term intravenous antibiotics and extensive physical therapy, Dr. Horowitz recovered. “I definitely had PTSD afterwards. How could a non-eventful bike ride result in an unrecognized threatening illness? I thought a healing opportunity for me and an educational opportunity for the medical staff and students at this medical center would be for me to present my case to them at a conference at their facility the next time I visited my daughter in California. I thought an experienced clinician discussing his own illness in his own specialty would be unique.”

The hospital ignored his offer.

By happenstance, a year and a half later, Dr. Horowitz made contact with a hospital administrator after hearing her speak during a TED Radio Hour in his car. “We had several telephone conversations and email correspondences in October and November 2019 but none since,” he said. In one email, she wrote that “hospitals don’t seem to know what to do with the opportunity you present. I don’t think the challenge is unique to [this institution]. A forum for these kinds of discussions – constructive, insightful patient feedback – does not exist.”

Dr. Horowitz hasn’t considered a malpractice lawsuit. “The only result would be a monetary reward based on damages. Since permanent clinical damage did not occur, the suit would have been time consuming and the reward limited. I was able to recover because I was able to review the blood work and recognize my own problem and get excellent care at my own local health care facility. I was really hoping the doctors at the California hospital would learn from this episode.”

Dr. Horowitz also wrote the Medical Board of California a detailed letter, citing relevant medical literature, guidelines on spinal care, and his test results. Nearly 2 years later, he finally got a response. The board said there was no “clear and convincing evidence that negligence took place.” In Dr. Horowitz’s opinion, “the fact that CRP was 30 times past normal is ‘clear and convincing evidence.’ That the consultant didn’t have a reflex hammer is also ‘clear and convincing evidence.’ That the clinical neurologic exam was incompetent, by any measure, is ‘clear and convincing evidence.’ Even the Medical Board, tasked with patient protection, didn’t recognize negligent medical care. They might have if I had become quadriplegic.”
 

A new normal?

Dr. Horowitz, who wrote of his experience in The Washington Post, said it reflects a persistent, systemic problem in health care: the inability to address medical errors and correct them. In the article, he addressed a phenomenon called the “the normalization of deviance.” Diane Vaughn wrote about this phenomenon in a 1997 book about the Space Shuttle disaster. Multiple flaws were noted in previous shuttle launches but then rationalized and “normalized” when they didn’t cause a disaster – until they ultimately did.

“That’s relevant to my situation,” Dr. Horowitz said. “The spine supervisor at this hospital excused the consultant by saying, ‘he did the exam to the best of his ability.’ Further, the response to my complaints came from hospital representatives rather than physicians, meaning that the ‘normalization’ was institutional, and it was willing to accept his poor performance without sanctions.”

He imagines that he could not be the only case handled poorly by this hospital or that particular consultant. “He could have done the same thing to another patient who didn’t have my medical knowledge,” added Dr. Horowitz.

In her book, Ms. Vaughan noted that whistleblower activity is sometimes the only device that reveals normalization of deviance.

Dr. Horowitz sees himself as a whistleblower for these types of mistakes. “The question is, how do we deal with medical errors even in sophisticated patients who see these errors, and how do you manage this in the average patient? I don’t want to see this type of medical care rendered for any patient, hence my attempt to make this situation public.”
 

A teachable moment lost?

Commenting on this case, Alan Rapoport, MD, said, “[it]illustrates inadequate physician evaluation in the ED, poor communication from the examining doctor about abnormal lab and MRI findings, unwillingness to call in consultants to properly evaluate the situation, and no recognition of the need to admit the patient.”

Dr. Rapoport is the editor in chief of Neurology Reviews and a clinical professor of neurology at UCLA in Los Angeles. He is a past president of the International Headache Society.

He noted that the patient is in his late 70s and needed to fly across the country to arrive at home. “Months later, when this situation was explained to the hospital via the mail, they totally failed to recognize their inadequacies and apologize for their mistakes. They were probably concerned about being sued, but I believe that their actions increased their chances of a lawsuit,” Dr. Rapoport said.

“When a teaching remedy was offered by the patient to the hospital so the doctors involved could learn from the experience, the hospital was not interested. The only party that learned from this unfortunate episode was the patient, not the doctors, or the ER, or the hospital administration,” Dr. Rapoport said.

He continued, “It is scary to think that an excellent hospital would act in this manner and refuse to learn from their mistakes. The California medical board was notified and did not investigate. It is not too late for the hospital to apologize, communicate their shortcomings, and fix the problem at multiple levels in the hospital.”

Dr. Rapoport consulted Morris Levin, MD, a professor of neurology and director of the Headache Program at UCSF, to ask what he thought, theoretically, about how a hospital should respond when they make a mistake and how much they should divulge. Dr. Levin is involved in Medical Ethics and often lectures about it at conferences.

Dr. Levin said, “When medical errors are made, to me, it is ethically sound to identify them and ‘fess up.’ There has always been reluctance to do so because of fears of lawsuits, but it turns out that when institutions do disclose errors, their liability costs actually go down.” Dr. Levin cited the University of Michigan, which tried a full disclosure policy as an experiment. “It led to reduced costs, not to mention a boost in patient satisfaction,” Dr. Levin noted.

He continued, “I think patients want and deserve to know the truth. I also believe they understand that medical errors can and will happen. It is my observation that patients have several key concerns: 1) how the error(s) happened, 2) how the error affected their health and what can be done to restore them to optimal health, and 3) what the institution is going to do to prevent this kind of error from happening to others.”

Dr. Rapoport concurs with Dr. Levin. “I am glad Dr. Horowitz has fully recovered and at least he has learned from the experience. I do not think the hospital and doctors did,” Dr. Rapoport said.

This article was updated 11/12/20.

When Steven Horowitz, MD, began experiencing neck and arm pain, numbness, and tingling following a bike ride several years ago, he immediately sought care at an elite medical center in California. As he recalls, an incompetent clinical exam and no access to highly abnormal test results done in the ED almost cost him his health. Had he listened to the doctors at that facility, he believes he would have become quadriplegic.

His training as a neurologist likely saved his life: “I was able to recover because, after arriving home, I reviewed my blood work and MRI online and recognized multiple problems.” He was able to get excellent care at his own local health care facility in Maine. The staff and leadership at the hospital in California wouldn’t admit wrongdoing, and efforts to seek recourse have proved fruitless, he said.

A lingering question nags at him: What if he had been an ordinary patient without medical expertise? What do his experiences say about the health care system’s management of medical omissions and errors?

Dr. Horowitz, 78 years old and retired, continues to teach medical students as an adjunct clinical professor of neurology at the Tufts University School of Medicine in Boston. He is also on the teaching faculty of the Maine Medical Center. He was professor and chief of neurology at a major university in the Midwest for many years.

In 2018, he visited his daughter on the West Coast, enjoying a day of biking. The neck pain began 5 or 6 hours after the ride and spread to his arms. “There was also numbness and tingling,” he said.
 

“I told them I was a neurologist”

The next day the pain got worse. Dr. Horowitz went to the ED of a nearby medical center with his daughter and immediately disclosed that he was a neurologist. “I did this for several reasons,” he explained. He wanted to alert staff that he had a cervical spine problem because “I wanted them to do a cervical MRI scan, and I wanted to read it because I’m capable of doing that.” He also related a past history of infection and antibiotic use and asked for C-reactive protein and erythrocyte sedimentation rate tests in addition to regular blood work. “Those inflammatory markers, if abnormal, would indicate an infection,” said Dr. Horowitz.

No reflex hammer or Babinski test

During the reflex exam with a spine consultant, Dr. Horowitz noticed that the consultant wasn’t using a reflex hammer, the clinical equivalent of evaluating the heart or lungs without a stethoscope. “I asked where the reflex hammer was, and he said he didn’t need one or own one. He used the inside of his hand. Apparently, there was some mild weakness in some muscle groups, but he didn’t address that,” said Dr. Horowitz. The consultant also didn’t test for the Babinski sign until reminded of it.

He took out a stethoscope and struck the middle of the soles of Dr. Horowitz’s feet. “I thought to myself, this consultant is the consultant for the spine service? How is it possible that he has a stethoscope and not a reflex hammer and didn’t know how to test for the Babinski sign?” The consultant also didn’t examine for gait, coordination, or hand dexterity. “He took his finger and touched my feet and legs. That was his sensory exam. He didn’t use a pin or a tuning fork” or other methods including touch, temperature, position sense, and vibration to assess sensory abnormalities that might signal spinal cord dysfunction.

An MRI at the hospital revealed a mass at the back of the neck. No contrast material was used during the MRI even though this step would have signaled the presence of infection. “Gadolinium should have been injected during the MRI because that would have strongly suggested that this mass in my neck was not a little blood clot and more likely an infection. They would have realized something more complicated than degenerative arthritis was going on. They told me that I had advanced spondylosis and that the mass was a hematoma. They told me not to worry about the blood results. Then they discharged me.”
 

A life-threatening discovery

Dr. Horowitz didn’t see the results of the blood work-up until returning to Maine a few days later, when he checked the online report. There was a highly elevated CRP level – 30 times above the normal limit – and elevated erythrocyte sedimentation rate and white blood cell counts. “This showed that there was an infective process going on. And it wasn’t just a localized process, it was in my bloodstream,” he said.

Alarmed by the elevated markers, he immediately went to his local hospital. “Not only did I have arthritis, but my spinal cord was compressed.” Urgent surgery was performed, including a C2-7 fusion. The mass in the back of his neck turned out to be an abscess.

His training and experience as a physician/neurologist saved him from further damage, he said. “Because the compression of the spine was at the C2, C3, C4 level, not only would I have become quadriplegic, but my diaphragm would likely have been paralyzed and I would have needed a ventilator.”

Following a month’s care in the hospital and a rehabilitation center, he wrote to the CEO of the California hospital where he received his initial care.

“I wrote about the incompetent exam, the missed infection, a discharge without information. I wrote all that out to the CEO and sent the letter registered so that he would receive it.” The CEO forwarded the letter to a patient risk manager, who interviewed staff and supervisors in the ED, radiology, and the spine program. They responded 3 months later. According to Dr. Horowitz, the spine supervisor said, “The consultant performed the exam to the best of his ability.” No one admitted to any errors in care or the lack of recognition of the infection, although the neuroradiologist did apologize for not allowing Dr. Horowitz to read his own MRI in a timely manner.

“They had promised to wheel a portable computer into my alcove so I could view the MRI.” Several hours later, after persistent complaints, he was given 1 minute to look over at least 300 images at a desktop computer in the crowded ED. They gave him the MRI images on a disk, but he wasn’t able to read it on his iMac computer.

According to Dr. Horowitz, the ED should have called in an infectious disease consultant and a neurologist or neurosurgeon to do a more complete neurologic exam. “Instead of discharging me, they should have admitted me, telling me that I had spinal cord compression, an infection, and a mass in my neck—that they don’t know what this is about, and I shouldn’t go home.”

Eventually, after long-term intravenous antibiotics and extensive physical therapy, Dr. Horowitz recovered. “I definitely had PTSD afterwards. How could a non-eventful bike ride result in an unrecognized threatening illness? I thought a healing opportunity for me and an educational opportunity for the medical staff and students at this medical center would be for me to present my case to them at a conference at their facility the next time I visited my daughter in California. I thought an experienced clinician discussing his own illness in his own specialty would be unique.”

The hospital ignored his offer.

By happenstance, a year and a half later, Dr. Horowitz made contact with a hospital administrator after hearing her speak during a TED Radio Hour in his car. “We had several telephone conversations and email correspondences in October and November 2019 but none since,” he said. In one email, she wrote that “hospitals don’t seem to know what to do with the opportunity you present. I don’t think the challenge is unique to [this institution]. A forum for these kinds of discussions – constructive, insightful patient feedback – does not exist.”

Dr. Horowitz hasn’t considered a malpractice lawsuit. “The only result would be a monetary reward based on damages. Since permanent clinical damage did not occur, the suit would have been time consuming and the reward limited. I was able to recover because I was able to review the blood work and recognize my own problem and get excellent care at my own local health care facility. I was really hoping the doctors at the California hospital would learn from this episode.”

Dr. Horowitz also wrote the Medical Board of California a detailed letter, citing relevant medical literature, guidelines on spinal care, and his test results. Nearly 2 years later, he finally got a response. The board said there was no “clear and convincing evidence that negligence took place.” In Dr. Horowitz’s opinion, “the fact that CRP was 30 times past normal is ‘clear and convincing evidence.’ That the consultant didn’t have a reflex hammer is also ‘clear and convincing evidence.’ That the clinical neurologic exam was incompetent, by any measure, is ‘clear and convincing evidence.’ Even the Medical Board, tasked with patient protection, didn’t recognize negligent medical care. They might have if I had become quadriplegic.”
 

A new normal?

Dr. Horowitz, who wrote of his experience in The Washington Post, said it reflects a persistent, systemic problem in health care: the inability to address medical errors and correct them. In the article, he addressed a phenomenon called the “the normalization of deviance.” Diane Vaughn wrote about this phenomenon in a 1997 book about the Space Shuttle disaster. Multiple flaws were noted in previous shuttle launches but then rationalized and “normalized” when they didn’t cause a disaster – until they ultimately did.

“That’s relevant to my situation,” Dr. Horowitz said. “The spine supervisor at this hospital excused the consultant by saying, ‘he did the exam to the best of his ability.’ Further, the response to my complaints came from hospital representatives rather than physicians, meaning that the ‘normalization’ was institutional, and it was willing to accept his poor performance without sanctions.”

He imagines that he could not be the only case handled poorly by this hospital or that particular consultant. “He could have done the same thing to another patient who didn’t have my medical knowledge,” added Dr. Horowitz.

In her book, Ms. Vaughan noted that whistleblower activity is sometimes the only device that reveals normalization of deviance.

Dr. Horowitz sees himself as a whistleblower for these types of mistakes. “The question is, how do we deal with medical errors even in sophisticated patients who see these errors, and how do you manage this in the average patient? I don’t want to see this type of medical care rendered for any patient, hence my attempt to make this situation public.”
 

A teachable moment lost?

Commenting on this case, Alan Rapoport, MD, said, “[it]illustrates inadequate physician evaluation in the ED, poor communication from the examining doctor about abnormal lab and MRI findings, unwillingness to call in consultants to properly evaluate the situation, and no recognition of the need to admit the patient.”

Dr. Rapoport is the editor in chief of Neurology Reviews and a clinical professor of neurology at UCLA in Los Angeles. He is a past president of the International Headache Society.

He noted that the patient is in his late 70s and needed to fly across the country to arrive at home. “Months later, when this situation was explained to the hospital via the mail, they totally failed to recognize their inadequacies and apologize for their mistakes. They were probably concerned about being sued, but I believe that their actions increased their chances of a lawsuit,” Dr. Rapoport said.

“When a teaching remedy was offered by the patient to the hospital so the doctors involved could learn from the experience, the hospital was not interested. The only party that learned from this unfortunate episode was the patient, not the doctors, or the ER, or the hospital administration,” Dr. Rapoport said.

He continued, “It is scary to think that an excellent hospital would act in this manner and refuse to learn from their mistakes. The California medical board was notified and did not investigate. It is not too late for the hospital to apologize, communicate their shortcomings, and fix the problem at multiple levels in the hospital.”

Dr. Rapoport consulted Morris Levin, MD, a professor of neurology and director of the Headache Program at UCSF, to ask what he thought, theoretically, about how a hospital should respond when they make a mistake and how much they should divulge. Dr. Levin is involved in Medical Ethics and often lectures about it at conferences.

Dr. Levin said, “When medical errors are made, to me, it is ethically sound to identify them and ‘fess up.’ There has always been reluctance to do so because of fears of lawsuits, but it turns out that when institutions do disclose errors, their liability costs actually go down.” Dr. Levin cited the University of Michigan, which tried a full disclosure policy as an experiment. “It led to reduced costs, not to mention a boost in patient satisfaction,” Dr. Levin noted.

He continued, “I think patients want and deserve to know the truth. I also believe they understand that medical errors can and will happen. It is my observation that patients have several key concerns: 1) how the error(s) happened, 2) how the error affected their health and what can be done to restore them to optimal health, and 3) what the institution is going to do to prevent this kind of error from happening to others.”

Dr. Rapoport concurs with Dr. Levin. “I am glad Dr. Horowitz has fully recovered and at least he has learned from the experience. I do not think the hospital and doctors did,” Dr. Rapoport said.

This article was updated 11/12/20.

Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.

Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.

“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
 

Symptom clusters verify smaller study’s findings

Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.

In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.

They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.

In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.

They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:

• Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
• Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
• Cluster 3 patients (34%) had predominant high dryness and fatigue.
• Cluster 4 patients (14%) had low symptom burden.

“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.

For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.

“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.

The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.

In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.

The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).

Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.

The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
 

Opportunity to tailor practice and research

During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.

“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”

Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.

Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.

The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.

SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.

Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.

Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.

“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
 

Symptom clusters verify smaller study’s findings

Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.

In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.

They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.

In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.

They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:

• Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
• Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
• Cluster 3 patients (34%) had predominant high dryness and fatigue.
• Cluster 4 patients (14%) had low symptom burden.

“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.

For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.

“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.

The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.

In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.

The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).

Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.

The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
 

Opportunity to tailor practice and research

During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.

“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”

Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.

Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.

The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.

SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.

Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.

Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.

“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
 

Symptom clusters verify smaller study’s findings

Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.

In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.

They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.

In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.

They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:

• Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
• Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
• Cluster 3 patients (34%) had predominant high dryness and fatigue.
• Cluster 4 patients (14%) had low symptom burden.

“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.

For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.

“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.

The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.

In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.

The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).

Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.

The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
 

Opportunity to tailor practice and research

During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.

“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”

Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.

Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.

The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.

SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.

Inflammatory bowel disease (IBD) is rapidly increasing among racial and ethnic minorities, which makes it important to consider for patients with compatible symptoms, experts wrote in Gastroenterology.

Crohn’s disease and ulcerative colitis are “chronic diseases with intermittent periods of flare and remission, so access to specialists, appropriate therapies, and frequent follow-up visits are vital to good outcomes,” wrote Edward L. Barnes, MD, MPH, of University of North Carolina at Chapel Hill, with his associates. However, Blacks with IBD tend to be diagnosed later than Whites, are less likely to receive recommended biologics and immunomodulators, and are more likely to receive care at an emergency department, to experience delays in colectomy, and to miss regular visits to IBD specialists because of financial and transportation barriers, they added.

These disparities are known to worsen outcomes. Compared with Whites, for example, Black patients with Crohn’s disease have higher rates of stricture and penetrating lesions and are at greater risk for postsurgical complications and death, even after potential confounders such age, sex, smoking status, time to operation, and obesity are controlled for. To help close these gaps, Dr. Barnes and his associates recommended enhanced recovery after surgery (ERAS) protocols, which “streamline [the] multidisciplinary management of patients with IBD before surgery, incorporating evidence-based practices focused on nutrition, prevention of postoperative ileus, and use of nonopioid analgesia and goal-directed fluid therapy.”

Similar approaches also might improve nonsurgical outcomes in minorities with IBD, the experts said. In the Sinai-Helmsley Alliance for Research Excellence (SHARE) study, Black patients had more complicated IBD at baseline but similar clinical outcomes and patterns of medication use as Whites when they were treated at academic IBD centers. In other studies, race and ethnicity did not affect patterns of medication use, surgery, or surgical outcomes if patients had similar access to care. Such findings “indicate that when patients of minority races and ethnicities have access to appropriate specialty care and IBD-related therapy, many previously identified disparities are resolved or reduced,” the experts said.

However, race and ethnicity do affect some aspects of IBD disease activity, genetics, and treatment safety and efficacy. Since White patients have made up the vast majority of research participants, studies of racial and ethnic minorities are needed to improve their IBD diagnosis, prevention, and treatment. Such research is particularly vital because IBD incidence is rising three times faster rates in racial and ethnic minorities than Whites, said Aline Charabaty, MD, AGAF, clinical director of the gastroenterology division at Johns Hopkins University in Baltimore, and director of the IBD Center at Sibley Memorial Hospital in Washington.

She explained that, when immigrants from countries where IBD is rare adopt the United States’ sedentary lifestyle and Western diet (low in fruits and vegetables; high in proinflammatory saturated fats, sugars, and processed foods), their gut microbiome shifts and their IBD risk increases markedly. Studies in other countries have produced similar findings, said Dr. Charabaty, who did not help author the review article.

She also noted that patients from communities with a historically low prevalence of IBD may not understand its chronicity or the need for long-term treatment. However, treatment adherence is a common issue for patients of all backgrounds with IBD, she said. “What is unique is barriers to continuity of care – not being able to get to the treatment center, not being able to afford treatment or take time off work if you live paycheck to paycheck, not being able to pay someone to care for your kids while you see the doctor.”

Other potential barriers to seeking IBD treatment include cultural taboos against discussing lower GI symptoms or concerns that chronic disease will harm marriage prospects, Dr. Charabaty said. Such challenges only heighten the need to ascertain IBD symptoms: “Studies show that minorities have less follow-up care and their symptoms tend to be minimized. There is a lot of unconscious bias among providers that factors into this. The barriers are multiple, and it is important to define them and find strategies to overcome them at the level of the patient, the clinician, and the health system.”

The Crohn’s and Colitis Foundation supported the work. Dr. Barnes disclosed ties to AbbVie, Gilead, Takeda, and Target Pharmasolutions. Two coauthors also disclosed relevant ties to pharmaceutical companies. Dr. Charabaty disclosed relationships with AbbVie, Takeda, Pfizer, Janssen, and UCB.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

SOURCE: Barnes EL et al. Gastroenterology. 2020 Oct 20. doi: 10.1053/j.gastro.2020.08.064.
 

Inflammatory bowel disease (IBD) is rapidly increasing among racial and ethnic minorities, which makes it important to consider for patients with compatible symptoms, experts wrote in Gastroenterology.

Crohn’s disease and ulcerative colitis are “chronic diseases with intermittent periods of flare and remission, so access to specialists, appropriate therapies, and frequent follow-up visits are vital to good outcomes,” wrote Edward L. Barnes, MD, MPH, of University of North Carolina at Chapel Hill, with his associates. However, Blacks with IBD tend to be diagnosed later than Whites, are less likely to receive recommended biologics and immunomodulators, and are more likely to receive care at an emergency department, to experience delays in colectomy, and to miss regular visits to IBD specialists because of financial and transportation barriers, they added.

These disparities are known to worsen outcomes. Compared with Whites, for example, Black patients with Crohn’s disease have higher rates of stricture and penetrating lesions and are at greater risk for postsurgical complications and death, even after potential confounders such age, sex, smoking status, time to operation, and obesity are controlled for. To help close these gaps, Dr. Barnes and his associates recommended enhanced recovery after surgery (ERAS) protocols, which “streamline [the] multidisciplinary management of patients with IBD before surgery, incorporating evidence-based practices focused on nutrition, prevention of postoperative ileus, and use of nonopioid analgesia and goal-directed fluid therapy.”

Similar approaches also might improve nonsurgical outcomes in minorities with IBD, the experts said. In the Sinai-Helmsley Alliance for Research Excellence (SHARE) study, Black patients had more complicated IBD at baseline but similar clinical outcomes and patterns of medication use as Whites when they were treated at academic IBD centers. In other studies, race and ethnicity did not affect patterns of medication use, surgery, or surgical outcomes if patients had similar access to care. Such findings “indicate that when patients of minority races and ethnicities have access to appropriate specialty care and IBD-related therapy, many previously identified disparities are resolved or reduced,” the experts said.

However, race and ethnicity do affect some aspects of IBD disease activity, genetics, and treatment safety and efficacy. Since White patients have made up the vast majority of research participants, studies of racial and ethnic minorities are needed to improve their IBD diagnosis, prevention, and treatment. Such research is particularly vital because IBD incidence is rising three times faster rates in racial and ethnic minorities than Whites, said Aline Charabaty, MD, AGAF, clinical director of the gastroenterology division at Johns Hopkins University in Baltimore, and director of the IBD Center at Sibley Memorial Hospital in Washington.

She explained that, when immigrants from countries where IBD is rare adopt the United States’ sedentary lifestyle and Western diet (low in fruits and vegetables; high in proinflammatory saturated fats, sugars, and processed foods), their gut microbiome shifts and their IBD risk increases markedly. Studies in other countries have produced similar findings, said Dr. Charabaty, who did not help author the review article.

She also noted that patients from communities with a historically low prevalence of IBD may not understand its chronicity or the need for long-term treatment. However, treatment adherence is a common issue for patients of all backgrounds with IBD, she said. “What is unique is barriers to continuity of care – not being able to get to the treatment center, not being able to afford treatment or take time off work if you live paycheck to paycheck, not being able to pay someone to care for your kids while you see the doctor.”

Other potential barriers to seeking IBD treatment include cultural taboos against discussing lower GI symptoms or concerns that chronic disease will harm marriage prospects, Dr. Charabaty said. Such challenges only heighten the need to ascertain IBD symptoms: “Studies show that minorities have less follow-up care and their symptoms tend to be minimized. There is a lot of unconscious bias among providers that factors into this. The barriers are multiple, and it is important to define them and find strategies to overcome them at the level of the patient, the clinician, and the health system.”

The Crohn’s and Colitis Foundation supported the work. Dr. Barnes disclosed ties to AbbVie, Gilead, Takeda, and Target Pharmasolutions. Two coauthors also disclosed relevant ties to pharmaceutical companies. Dr. Charabaty disclosed relationships with AbbVie, Takeda, Pfizer, Janssen, and UCB.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

SOURCE: Barnes EL et al. Gastroenterology. 2020 Oct 20. doi: 10.1053/j.gastro.2020.08.064.
 

Inflammatory bowel disease (IBD) is rapidly increasing among racial and ethnic minorities, which makes it important to consider for patients with compatible symptoms, experts wrote in Gastroenterology.

Crohn’s disease and ulcerative colitis are “chronic diseases with intermittent periods of flare and remission, so access to specialists, appropriate therapies, and frequent follow-up visits are vital to good outcomes,” wrote Edward L. Barnes, MD, MPH, of University of North Carolina at Chapel Hill, with his associates. However, Blacks with IBD tend to be diagnosed later than Whites, are less likely to receive recommended biologics and immunomodulators, and are more likely to receive care at an emergency department, to experience delays in colectomy, and to miss regular visits to IBD specialists because of financial and transportation barriers, they added.

These disparities are known to worsen outcomes. Compared with Whites, for example, Black patients with Crohn’s disease have higher rates of stricture and penetrating lesions and are at greater risk for postsurgical complications and death, even after potential confounders such age, sex, smoking status, time to operation, and obesity are controlled for. To help close these gaps, Dr. Barnes and his associates recommended enhanced recovery after surgery (ERAS) protocols, which “streamline [the] multidisciplinary management of patients with IBD before surgery, incorporating evidence-based practices focused on nutrition, prevention of postoperative ileus, and use of nonopioid analgesia and goal-directed fluid therapy.”

Similar approaches also might improve nonsurgical outcomes in minorities with IBD, the experts said. In the Sinai-Helmsley Alliance for Research Excellence (SHARE) study, Black patients had more complicated IBD at baseline but similar clinical outcomes and patterns of medication use as Whites when they were treated at academic IBD centers. In other studies, race and ethnicity did not affect patterns of medication use, surgery, or surgical outcomes if patients had similar access to care. Such findings “indicate that when patients of minority races and ethnicities have access to appropriate specialty care and IBD-related therapy, many previously identified disparities are resolved or reduced,” the experts said.

However, race and ethnicity do affect some aspects of IBD disease activity, genetics, and treatment safety and efficacy. Since White patients have made up the vast majority of research participants, studies of racial and ethnic minorities are needed to improve their IBD diagnosis, prevention, and treatment. Such research is particularly vital because IBD incidence is rising three times faster rates in racial and ethnic minorities than Whites, said Aline Charabaty, MD, AGAF, clinical director of the gastroenterology division at Johns Hopkins University in Baltimore, and director of the IBD Center at Sibley Memorial Hospital in Washington.

She explained that, when immigrants from countries where IBD is rare adopt the United States’ sedentary lifestyle and Western diet (low in fruits and vegetables; high in proinflammatory saturated fats, sugars, and processed foods), their gut microbiome shifts and their IBD risk increases markedly. Studies in other countries have produced similar findings, said Dr. Charabaty, who did not help author the review article.

She also noted that patients from communities with a historically low prevalence of IBD may not understand its chronicity or the need for long-term treatment. However, treatment adherence is a common issue for patients of all backgrounds with IBD, she said. “What is unique is barriers to continuity of care – not being able to get to the treatment center, not being able to afford treatment or take time off work if you live paycheck to paycheck, not being able to pay someone to care for your kids while you see the doctor.”

Other potential barriers to seeking IBD treatment include cultural taboos against discussing lower GI symptoms or concerns that chronic disease will harm marriage prospects, Dr. Charabaty said. Such challenges only heighten the need to ascertain IBD symptoms: “Studies show that minorities have less follow-up care and their symptoms tend to be minimized. There is a lot of unconscious bias among providers that factors into this. The barriers are multiple, and it is important to define them and find strategies to overcome them at the level of the patient, the clinician, and the health system.”

The Crohn’s and Colitis Foundation supported the work. Dr. Barnes disclosed ties to AbbVie, Gilead, Takeda, and Target Pharmasolutions. Two coauthors also disclosed relevant ties to pharmaceutical companies. Dr. Charabaty disclosed relationships with AbbVie, Takeda, Pfizer, Janssen, and UCB.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

SOURCE: Barnes EL et al. Gastroenterology. 2020 Oct 20. doi: 10.1053/j.gastro.2020.08.064.
 

No significant differences in major adverse cardiovascular events (MACE) emerged between methotrexate and hydroxychloroquine (HCQ) treatment in a comparison of adults 65 years or older with rheumatoid arthritis. However, researchers reported some elevation in risk for stroke in the methotrexate group and for myocardial infarction and heart failure in the HCQ group.

The primary outcome, a composite of MI, stroke, or cardiovascular death, had an incidence of 23.39 per 1,000 person-years in the methotrexate group versus 24.33 in the HCQ group in this observational study of nearly 60,000 people.

“These results suggest an importance of looking at different individual events of cardiovascular disease rather than the whole ‘CV’ disease only,” Seoyoung Kim, MD, said in an interview. “The other important thing is that the mortality was not significantly different between the two groups.”

For example, the researchers reported 256 cardiovascular-related deaths in the methotrexate group and 263 such deaths in the HCQ cohort.
 

Addressing a recognized risk

“It is well known that patients with rheumatoid arthritis have excessive morbidity and mortality,” Dr. Kim, of the division of rheumatology at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School in Boston, said at the virtual annual meeting of the American College of Rheumatology.

Among prior studies in this area, the Cardiovascular Inflammation Reduction Trial (CIRT) found no significant reduction in cardiovascular events among people taking methotrexate versus placebo. However, the study of 4,786 people was not specific to RA, Dr. Kim said. The lack of efficacy on this endpoint prompted researchers to stop CIRT early.

“So what does the conclusion of the CIRT trial mean for rheumatoid arthritis patients?” Dr. Kim asked.

To find out, she and colleagues compared risk of MACE among participants newly starting either methotrexate or HCQ. The study included 59,329 people aged 65 and older who were identified through Medicare claims data from 2008 to 2016. Mean age was 74 years, and 80% were women.

The investigators used propensity score matching to control for multiple covariates for demographics, other medications, and comorbidities. Use of other medications was similar between groups, including glucocorticoids, NSAIDs, and statins. Baseline cardiovascular morbidities likewise were well balanced, Dr. Kim said.

The hazard ratio for the primary MACE outcome was 0.96 (95% confidence interval, 0.86-1.08).

Secondary outcomes

MI was less common in the methotrexate group, for example, with an incidence of 8.49 per 1,000 person-years versus 10.68 per 1,000 person-years in the HCQ cohort. This finding was statically significant, Dr. Kim said, with a hazard ratio of 0.80 favoring methotrexate.

Heart failure also occurred less often in the methotrexate cohort, with an incidence rate of 8.57 per 1,000 person-years versus a rate of 14.24 in the HCQ group. The hazard ratio again favored methotrexate at 0.60.

In contrast, strokes were more common with methotrexate than with (incidence of 7.94 vs. 6.01 per 1,000 person-years).

Another secondary outcome, all-cause mortality, was not significantly different between groups. There were 821 deaths in the methotrexate group (28.65 per 1,000 person-years) and 796 deaths in the HCQ group (31.33 per 1,000 person-years).
 

Studying causality next?

Session moderator Maya Buch, MD, PhD, professor of rheumatology at the University of Manchester (England), asked Dr. Kim why she found significant differences in some secondary outcomes but not the primary composite endpoint.

“When we think of cardiovascular diseases, we tend to think of them all developing through the same mechanism. But perhaps the exact mechanism might not be identical,” Dr. Kim replied. The findings do not suggest causality because the study was observational, she added, “but maybe this will lead to a randomized, controlled trial.”

When asked for comment, Dr. Buch said that the study was “interesting” and “suggestive of differences in type of MACE between the two drugs evaluated,” but that there should be caution in interpreting the findings because of the lack of detailed information on RA disease and activity in claims databases, in addition to other factors, even though the investigators made adjustments for known differences through propensity score matching.

The division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital supported the study. Dr. Kim has received support for Brigham and Women’s Hospital for unrelated research from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb. Several other coauthors reported having financial relationships with pharmaceutical companies that make drugs for RA. Dr. Buch had no relevant disclosures.

SOURCE: He M et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 1993.

No significant differences in major adverse cardiovascular events (MACE) emerged between methotrexate and hydroxychloroquine (HCQ) treatment in a comparison of adults 65 years or older with rheumatoid arthritis. However, researchers reported some elevation in risk for stroke in the methotrexate group and for myocardial infarction and heart failure in the HCQ group.

The primary outcome, a composite of MI, stroke, or cardiovascular death, had an incidence of 23.39 per 1,000 person-years in the methotrexate group versus 24.33 in the HCQ group in this observational study of nearly 60,000 people.

“These results suggest an importance of looking at different individual events of cardiovascular disease rather than the whole ‘CV’ disease only,” Seoyoung Kim, MD, said in an interview. “The other important thing is that the mortality was not significantly different between the two groups.”

For example, the researchers reported 256 cardiovascular-related deaths in the methotrexate group and 263 such deaths in the HCQ cohort.
 

Addressing a recognized risk

“It is well known that patients with rheumatoid arthritis have excessive morbidity and mortality,” Dr. Kim, of the division of rheumatology at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School in Boston, said at the virtual annual meeting of the American College of Rheumatology.

Among prior studies in this area, the Cardiovascular Inflammation Reduction Trial (CIRT) found no significant reduction in cardiovascular events among people taking methotrexate versus placebo. However, the study of 4,786 people was not specific to RA, Dr. Kim said. The lack of efficacy on this endpoint prompted researchers to stop CIRT early.

“So what does the conclusion of the CIRT trial mean for rheumatoid arthritis patients?” Dr. Kim asked.

To find out, she and colleagues compared risk of MACE among participants newly starting either methotrexate or HCQ. The study included 59,329 people aged 65 and older who were identified through Medicare claims data from 2008 to 2016. Mean age was 74 years, and 80% were women.

The investigators used propensity score matching to control for multiple covariates for demographics, other medications, and comorbidities. Use of other medications was similar between groups, including glucocorticoids, NSAIDs, and statins. Baseline cardiovascular morbidities likewise were well balanced, Dr. Kim said.

The hazard ratio for the primary MACE outcome was 0.96 (95% confidence interval, 0.86-1.08).

Secondary outcomes

MI was less common in the methotrexate group, for example, with an incidence of 8.49 per 1,000 person-years versus 10.68 per 1,000 person-years in the HCQ cohort. This finding was statically significant, Dr. Kim said, with a hazard ratio of 0.80 favoring methotrexate.

Heart failure also occurred less often in the methotrexate cohort, with an incidence rate of 8.57 per 1,000 person-years versus a rate of 14.24 in the HCQ group. The hazard ratio again favored methotrexate at 0.60.

In contrast, strokes were more common with methotrexate than with (incidence of 7.94 vs. 6.01 per 1,000 person-years).

Another secondary outcome, all-cause mortality, was not significantly different between groups. There were 821 deaths in the methotrexate group (28.65 per 1,000 person-years) and 796 deaths in the HCQ group (31.33 per 1,000 person-years).
 

Studying causality next?

Session moderator Maya Buch, MD, PhD, professor of rheumatology at the University of Manchester (England), asked Dr. Kim why she found significant differences in some secondary outcomes but not the primary composite endpoint.

“When we think of cardiovascular diseases, we tend to think of them all developing through the same mechanism. But perhaps the exact mechanism might not be identical,” Dr. Kim replied. The findings do not suggest causality because the study was observational, she added, “but maybe this will lead to a randomized, controlled trial.”

When asked for comment, Dr. Buch said that the study was “interesting” and “suggestive of differences in type of MACE between the two drugs evaluated,” but that there should be caution in interpreting the findings because of the lack of detailed information on RA disease and activity in claims databases, in addition to other factors, even though the investigators made adjustments for known differences through propensity score matching.

The division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital supported the study. Dr. Kim has received support for Brigham and Women’s Hospital for unrelated research from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb. Several other coauthors reported having financial relationships with pharmaceutical companies that make drugs for RA. Dr. Buch had no relevant disclosures.

SOURCE: He M et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 1993.

No significant differences in major adverse cardiovascular events (MACE) emerged between methotrexate and hydroxychloroquine (HCQ) treatment in a comparison of adults 65 years or older with rheumatoid arthritis. However, researchers reported some elevation in risk for stroke in the methotrexate group and for myocardial infarction and heart failure in the HCQ group.

The primary outcome, a composite of MI, stroke, or cardiovascular death, had an incidence of 23.39 per 1,000 person-years in the methotrexate group versus 24.33 in the HCQ group in this observational study of nearly 60,000 people.

“These results suggest an importance of looking at different individual events of cardiovascular disease rather than the whole ‘CV’ disease only,” Seoyoung Kim, MD, said in an interview. “The other important thing is that the mortality was not significantly different between the two groups.”

For example, the researchers reported 256 cardiovascular-related deaths in the methotrexate group and 263 such deaths in the HCQ cohort.
 

Addressing a recognized risk

“It is well known that patients with rheumatoid arthritis have excessive morbidity and mortality,” Dr. Kim, of the division of rheumatology at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School in Boston, said at the virtual annual meeting of the American College of Rheumatology.

Among prior studies in this area, the Cardiovascular Inflammation Reduction Trial (CIRT) found no significant reduction in cardiovascular events among people taking methotrexate versus placebo. However, the study of 4,786 people was not specific to RA, Dr. Kim said. The lack of efficacy on this endpoint prompted researchers to stop CIRT early.

“So what does the conclusion of the CIRT trial mean for rheumatoid arthritis patients?” Dr. Kim asked.

To find out, she and colleagues compared risk of MACE among participants newly starting either methotrexate or HCQ. The study included 59,329 people aged 65 and older who were identified through Medicare claims data from 2008 to 2016. Mean age was 74 years, and 80% were women.

The investigators used propensity score matching to control for multiple covariates for demographics, other medications, and comorbidities. Use of other medications was similar between groups, including glucocorticoids, NSAIDs, and statins. Baseline cardiovascular morbidities likewise were well balanced, Dr. Kim said.

The hazard ratio for the primary MACE outcome was 0.96 (95% confidence interval, 0.86-1.08).

Secondary outcomes

MI was less common in the methotrexate group, for example, with an incidence of 8.49 per 1,000 person-years versus 10.68 per 1,000 person-years in the HCQ cohort. This finding was statically significant, Dr. Kim said, with a hazard ratio of 0.80 favoring methotrexate.

Heart failure also occurred less often in the methotrexate cohort, with an incidence rate of 8.57 per 1,000 person-years versus a rate of 14.24 in the HCQ group. The hazard ratio again favored methotrexate at 0.60.

In contrast, strokes were more common with methotrexate than with (incidence of 7.94 vs. 6.01 per 1,000 person-years).

Another secondary outcome, all-cause mortality, was not significantly different between groups. There were 821 deaths in the methotrexate group (28.65 per 1,000 person-years) and 796 deaths in the HCQ group (31.33 per 1,000 person-years).
 

Studying causality next?

Session moderator Maya Buch, MD, PhD, professor of rheumatology at the University of Manchester (England), asked Dr. Kim why she found significant differences in some secondary outcomes but not the primary composite endpoint.

“When we think of cardiovascular diseases, we tend to think of them all developing through the same mechanism. But perhaps the exact mechanism might not be identical,” Dr. Kim replied. The findings do not suggest causality because the study was observational, she added, “but maybe this will lead to a randomized, controlled trial.”

When asked for comment, Dr. Buch said that the study was “interesting” and “suggestive of differences in type of MACE between the two drugs evaluated,” but that there should be caution in interpreting the findings because of the lack of detailed information on RA disease and activity in claims databases, in addition to other factors, even though the investigators made adjustments for known differences through propensity score matching.

The division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital supported the study. Dr. Kim has received support for Brigham and Women’s Hospital for unrelated research from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb. Several other coauthors reported having financial relationships with pharmaceutical companies that make drugs for RA. Dr. Buch had no relevant disclosures.

SOURCE: He M et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 1993.