During normal times, the U.K.-based charity No Panic offers itself as an easily accessible service to those with anxiety disorders and phobias. Visitors to the website who can receive immediate, remote support from trained volunteers. But this spring was anything but normal, as the reality of COVID-19’s worldwide spread became terrifyingly clear.

COVID-19 cases peaked in the United Kingdom in early April. Nationwide lockdown efforts contributed to a gradual but ultimately substantial decline in cases, yet, despite the favorable trend lines, No Panic has remained busier than ever.

Beyond the physical symptoms associated with COVID-19, the psychological outcomes are vast and, it seems, prolonged. Researchers have now formalized a definition of the long-term mental maladies associated with the pandemic, collectively deeming them “coronaphobia.”

The term is a catch-all phrase for the fear and the emotional and social strain experienced by the general public in response to COVID-19. Obsessive behaviors, distress, avoidance reaction, panic, anxiety, hoarding, paranoia, and depression are some of the responses associated with coronaphobia. On the surface, these appear to be normal, somewhat fitting reactions to this surreal and frightening moment in time. However, for those experiencing coronaphobia, they are distinctly maladaptive and harmful.

“We had a serious rise in the use of our services, notably the helpline and email enquiries,” explained Sarah Floyd, No Panic’s volunteer advisor and social media coordinator. “It has been up and down all along, but more of an up since lockdown is easing.”

The group’s experience offers yet more evidence that the anxieties and fears caused by this global pandemic don’t flatten alongside the curve but instead linger as chronic problems requiring ongoing care.

“Every week in my clinic, I’m seeing people who are experiencing more anxiety and hopelessness and having an emotional response that is perhaps out of proportion to what one would expect, which is directly related to what is going on in the world right now with coronavirus,” said Gregory Scott Brown, MD, founder and director of the Center for Green Psychiatry in West Lake Hills, Tex. “Simply put, I think what we are looking at is adjustment disorder. That is probably how the DSM would define it.”

Adjustment disorder is one of the most frequently diagnosed mental health conditions, although it is also relatively understudied. It is really a set of disorders that follow in the wake of a significant stressor, which can vary from serious illness or the death of a loved one to relocating or experiencing work problems. The resulting dysfunction and distress that the person experiences are considered out of proportion in duration or scale with what would normally be expected. Diagnosing an adjustment disorder is made difficult by the lack of a valid and reliable screening measure.

Recent literature suggests that coronaphobia may be likely to occur in those who feel vulnerable to disease, are predisposed to anxiety, or are intolerant of uncertainty. Preexisting mental health conditions can also be exacerbated by periods of quarantine, self-isolation, and lockdown, which can lead to panic attacks, chronophobia (fear of passing time), and suicidality.

Although imperfect comparisons, findings from earlier 21st century disease outbreaks, such as severe acute respiratory syndrome and the Ebola virus, signal that containment efforts themselves play a role in deteriorating mental health. A recent rapid review found that, in studies comparing persons who had previously undergone quarantines and those who had not, the former were significantly more likely to experience acute stress disorder, posttraumatic stress symptoms, and depression. Quarantine was found to result in long-term behavioral changes, such as avoiding crowds, among the general public and health care practitioners.

That tremendous psychological morbidity should accompany a global pandemic of this scale is not surprising, according to Amit Anand, MD, vice chair for research for the Center for Behavioral Health and director of the Mood and Emotional Disorders Across the Life Span program at the Cleveland Clinic.

“The technical definition of anxiety is an impending sense of doom, and I think all of us are living with that,” Dr. Anand said. “The basic question then becomes, what is normal and when does it become abnormal?”

He added that most classifications of psychiatric disorders are set during periods of relative stability, which the current moment is most certainly not.

“This is such an unusual situation, so I think it will depend on case-by-case basis, keeping the whole context in mind as whether the patient is thinking or behaving with an abnormal amount of anxiety,” Dr. Anand said.

Investigators are currently trying to give clinicians the tools to better make that determination. In the first scientific study of this clinical condition, Sherman Lee, MD, reported that five symptoms – dizziness, sleep disturbances, tonic immobility, appetite loss, and nausea/abdominal distress – were strong factors for distinguishing coronaphobia from otherwise normal concerns about COVID-19 that did not result in functional impairment. Dr. Lee and colleagues have since published further evidence that coronaphobia “is a unique predictor of psychological distress during the COVID-19 crisis.” They are working on validating a self-reported mental health screener for this condition.

Having the tools to identify patients struggling with coronaphobia may go some ways toward addressing another area of declining health. At the outset of the COVID-19 pandemic, there was a question as to whether doctors would be beset by a surge of the “worried well” – persons mistakenly believing themselves to be infected. Now months into the pandemic, the converse phenomenon – a fear of contracting COVID-19 that is driving patients away from practitioners – appears to be the more valid concern.

In early spring, the pandemic’s first surge was accompanied by reports of approximately 40% and 60% drops in visits to EDs and ambulatory centers, respectively. Stories of acute stroke patients avoiding treatment began to appear in the press. Major U.S. cities saw noteworthy declines in 911 calls, indicating a hesitancy to be taken to a hospital. That COVID-19 has been accompanied by mass unemployment and subsequent loss of insurance complicates the notion that fear alone is keeping people from treatment. In other countries, it has been explicitly linked. Investigators in Singapore noted that coronaphobia played a role in reducing willingness to attend in-person visits among adolescents with eating disorders. Similarly, case reports in Israel suggest that coronaphobia has contributed to delays in diagnoses of common pediatric diseases.

There is also a concern, colloquially termed “reentry anxiety,” that mental health problems caused by the pandemic, the accompanying lockdown, self-isolation, and quarantine practices will prove alarmingly durable. Even after this challenging moment in history draws to a close, many people may face substantial stress in returning to the normal activities of life – social, professional, familial – once taken for granted.

“We are in the beginning phase of that now,” said Dr. Anand. “Lots of people are decompensating, getting depressed, and needing treatment. I think the longer it goes on for, the more difficult it will be.”

In the United States, that day may seem far away. Nonetheless, it is important to begin laying the therapeutic groundwork now, according to Dr. Brown.

“I am recommending unconventional therapies like meet-up groups, online forums,” he said. “Everything has shifted online, and so there are a lot of support groups that patients can participate to learn coping skills and really hear what other people are going through.”

Before reaching that stage, Dr. Brown recommends that clinicians first simply discuss such anxieties with their patients in order to normalize them.

“Realize that everyone essentially is going through some degree of this right now. The coronavirus pandemic is literally impacting every person on the face of the planet. Sometimes just pointing that out to people can really help,” he said.

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

During normal times, the U.K.-based charity No Panic offers itself as an easily accessible service to those with anxiety disorders and phobias. Visitors to the website who can receive immediate, remote support from trained volunteers. But this spring was anything but normal, as the reality of COVID-19’s worldwide spread became terrifyingly clear.

COVID-19 cases peaked in the United Kingdom in early April. Nationwide lockdown efforts contributed to a gradual but ultimately substantial decline in cases, yet, despite the favorable trend lines, No Panic has remained busier than ever.

Beyond the physical symptoms associated with COVID-19, the psychological outcomes are vast and, it seems, prolonged. Researchers have now formalized a definition of the long-term mental maladies associated with the pandemic, collectively deeming them “coronaphobia.”

The term is a catch-all phrase for the fear and the emotional and social strain experienced by the general public in response to COVID-19. Obsessive behaviors, distress, avoidance reaction, panic, anxiety, hoarding, paranoia, and depression are some of the responses associated with coronaphobia. On the surface, these appear to be normal, somewhat fitting reactions to this surreal and frightening moment in time. However, for those experiencing coronaphobia, they are distinctly maladaptive and harmful.

“We had a serious rise in the use of our services, notably the helpline and email enquiries,” explained Sarah Floyd, No Panic’s volunteer advisor and social media coordinator. “It has been up and down all along, but more of an up since lockdown is easing.”

The group’s experience offers yet more evidence that the anxieties and fears caused by this global pandemic don’t flatten alongside the curve but instead linger as chronic problems requiring ongoing care.

“Every week in my clinic, I’m seeing people who are experiencing more anxiety and hopelessness and having an emotional response that is perhaps out of proportion to what one would expect, which is directly related to what is going on in the world right now with coronavirus,” said Gregory Scott Brown, MD, founder and director of the Center for Green Psychiatry in West Lake Hills, Tex. “Simply put, I think what we are looking at is adjustment disorder. That is probably how the DSM would define it.”

Adjustment disorder is one of the most frequently diagnosed mental health conditions, although it is also relatively understudied. It is really a set of disorders that follow in the wake of a significant stressor, which can vary from serious illness or the death of a loved one to relocating or experiencing work problems. The resulting dysfunction and distress that the person experiences are considered out of proportion in duration or scale with what would normally be expected. Diagnosing an adjustment disorder is made difficult by the lack of a valid and reliable screening measure.

Recent literature suggests that coronaphobia may be likely to occur in those who feel vulnerable to disease, are predisposed to anxiety, or are intolerant of uncertainty. Preexisting mental health conditions can also be exacerbated by periods of quarantine, self-isolation, and lockdown, which can lead to panic attacks, chronophobia (fear of passing time), and suicidality.

Although imperfect comparisons, findings from earlier 21st century disease outbreaks, such as severe acute respiratory syndrome and the Ebola virus, signal that containment efforts themselves play a role in deteriorating mental health. A recent rapid review found that, in studies comparing persons who had previously undergone quarantines and those who had not, the former were significantly more likely to experience acute stress disorder, posttraumatic stress symptoms, and depression. Quarantine was found to result in long-term behavioral changes, such as avoiding crowds, among the general public and health care practitioners.

That tremendous psychological morbidity should accompany a global pandemic of this scale is not surprising, according to Amit Anand, MD, vice chair for research for the Center for Behavioral Health and director of the Mood and Emotional Disorders Across the Life Span program at the Cleveland Clinic.

“The technical definition of anxiety is an impending sense of doom, and I think all of us are living with that,” Dr. Anand said. “The basic question then becomes, what is normal and when does it become abnormal?”

He added that most classifications of psychiatric disorders are set during periods of relative stability, which the current moment is most certainly not.

“This is such an unusual situation, so I think it will depend on case-by-case basis, keeping the whole context in mind as whether the patient is thinking or behaving with an abnormal amount of anxiety,” Dr. Anand said.

Investigators are currently trying to give clinicians the tools to better make that determination. In the first scientific study of this clinical condition, Sherman Lee, MD, reported that five symptoms – dizziness, sleep disturbances, tonic immobility, appetite loss, and nausea/abdominal distress – were strong factors for distinguishing coronaphobia from otherwise normal concerns about COVID-19 that did not result in functional impairment. Dr. Lee and colleagues have since published further evidence that coronaphobia “is a unique predictor of psychological distress during the COVID-19 crisis.” They are working on validating a self-reported mental health screener for this condition.

Having the tools to identify patients struggling with coronaphobia may go some ways toward addressing another area of declining health. At the outset of the COVID-19 pandemic, there was a question as to whether doctors would be beset by a surge of the “worried well” – persons mistakenly believing themselves to be infected. Now months into the pandemic, the converse phenomenon – a fear of contracting COVID-19 that is driving patients away from practitioners – appears to be the more valid concern.

In early spring, the pandemic’s first surge was accompanied by reports of approximately 40% and 60% drops in visits to EDs and ambulatory centers, respectively. Stories of acute stroke patients avoiding treatment began to appear in the press. Major U.S. cities saw noteworthy declines in 911 calls, indicating a hesitancy to be taken to a hospital. That COVID-19 has been accompanied by mass unemployment and subsequent loss of insurance complicates the notion that fear alone is keeping people from treatment. In other countries, it has been explicitly linked. Investigators in Singapore noted that coronaphobia played a role in reducing willingness to attend in-person visits among adolescents with eating disorders. Similarly, case reports in Israel suggest that coronaphobia has contributed to delays in diagnoses of common pediatric diseases.

There is also a concern, colloquially termed “reentry anxiety,” that mental health problems caused by the pandemic, the accompanying lockdown, self-isolation, and quarantine practices will prove alarmingly durable. Even after this challenging moment in history draws to a close, many people may face substantial stress in returning to the normal activities of life – social, professional, familial – once taken for granted.

“We are in the beginning phase of that now,” said Dr. Anand. “Lots of people are decompensating, getting depressed, and needing treatment. I think the longer it goes on for, the more difficult it will be.”

In the United States, that day may seem far away. Nonetheless, it is important to begin laying the therapeutic groundwork now, according to Dr. Brown.

“I am recommending unconventional therapies like meet-up groups, online forums,” he said. “Everything has shifted online, and so there are a lot of support groups that patients can participate to learn coping skills and really hear what other people are going through.”

Before reaching that stage, Dr. Brown recommends that clinicians first simply discuss such anxieties with their patients in order to normalize them.

“Realize that everyone essentially is going through some degree of this right now. The coronavirus pandemic is literally impacting every person on the face of the planet. Sometimes just pointing that out to people can really help,” he said.

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

During normal times, the U.K.-based charity No Panic offers itself as an easily accessible service to those with anxiety disorders and phobias. Visitors to the website who can receive immediate, remote support from trained volunteers. But this spring was anything but normal, as the reality of COVID-19’s worldwide spread became terrifyingly clear.

COVID-19 cases peaked in the United Kingdom in early April. Nationwide lockdown efforts contributed to a gradual but ultimately substantial decline in cases, yet, despite the favorable trend lines, No Panic has remained busier than ever.

Beyond the physical symptoms associated with COVID-19, the psychological outcomes are vast and, it seems, prolonged. Researchers have now formalized a definition of the long-term mental maladies associated with the pandemic, collectively deeming them “coronaphobia.”

The term is a catch-all phrase for the fear and the emotional and social strain experienced by the general public in response to COVID-19. Obsessive behaviors, distress, avoidance reaction, panic, anxiety, hoarding, paranoia, and depression are some of the responses associated with coronaphobia. On the surface, these appear to be normal, somewhat fitting reactions to this surreal and frightening moment in time. However, for those experiencing coronaphobia, they are distinctly maladaptive and harmful.

“We had a serious rise in the use of our services, notably the helpline and email enquiries,” explained Sarah Floyd, No Panic’s volunteer advisor and social media coordinator. “It has been up and down all along, but more of an up since lockdown is easing.”

The group’s experience offers yet more evidence that the anxieties and fears caused by this global pandemic don’t flatten alongside the curve but instead linger as chronic problems requiring ongoing care.

“Every week in my clinic, I’m seeing people who are experiencing more anxiety and hopelessness and having an emotional response that is perhaps out of proportion to what one would expect, which is directly related to what is going on in the world right now with coronavirus,” said Gregory Scott Brown, MD, founder and director of the Center for Green Psychiatry in West Lake Hills, Tex. “Simply put, I think what we are looking at is adjustment disorder. That is probably how the DSM would define it.”

Adjustment disorder is one of the most frequently diagnosed mental health conditions, although it is also relatively understudied. It is really a set of disorders that follow in the wake of a significant stressor, which can vary from serious illness or the death of a loved one to relocating or experiencing work problems. The resulting dysfunction and distress that the person experiences are considered out of proportion in duration or scale with what would normally be expected. Diagnosing an adjustment disorder is made difficult by the lack of a valid and reliable screening measure.

Recent literature suggests that coronaphobia may be likely to occur in those who feel vulnerable to disease, are predisposed to anxiety, or are intolerant of uncertainty. Preexisting mental health conditions can also be exacerbated by periods of quarantine, self-isolation, and lockdown, which can lead to panic attacks, chronophobia (fear of passing time), and suicidality.

Although imperfect comparisons, findings from earlier 21st century disease outbreaks, such as severe acute respiratory syndrome and the Ebola virus, signal that containment efforts themselves play a role in deteriorating mental health. A recent rapid review found that, in studies comparing persons who had previously undergone quarantines and those who had not, the former were significantly more likely to experience acute stress disorder, posttraumatic stress symptoms, and depression. Quarantine was found to result in long-term behavioral changes, such as avoiding crowds, among the general public and health care practitioners.

That tremendous psychological morbidity should accompany a global pandemic of this scale is not surprising, according to Amit Anand, MD, vice chair for research for the Center for Behavioral Health and director of the Mood and Emotional Disorders Across the Life Span program at the Cleveland Clinic.

“The technical definition of anxiety is an impending sense of doom, and I think all of us are living with that,” Dr. Anand said. “The basic question then becomes, what is normal and when does it become abnormal?”

He added that most classifications of psychiatric disorders are set during periods of relative stability, which the current moment is most certainly not.

“This is such an unusual situation, so I think it will depend on case-by-case basis, keeping the whole context in mind as whether the patient is thinking or behaving with an abnormal amount of anxiety,” Dr. Anand said.

Investigators are currently trying to give clinicians the tools to better make that determination. In the first scientific study of this clinical condition, Sherman Lee, MD, reported that five symptoms – dizziness, sleep disturbances, tonic immobility, appetite loss, and nausea/abdominal distress – were strong factors for distinguishing coronaphobia from otherwise normal concerns about COVID-19 that did not result in functional impairment. Dr. Lee and colleagues have since published further evidence that coronaphobia “is a unique predictor of psychological distress during the COVID-19 crisis.” They are working on validating a self-reported mental health screener for this condition.

Having the tools to identify patients struggling with coronaphobia may go some ways toward addressing another area of declining health. At the outset of the COVID-19 pandemic, there was a question as to whether doctors would be beset by a surge of the “worried well” – persons mistakenly believing themselves to be infected. Now months into the pandemic, the converse phenomenon – a fear of contracting COVID-19 that is driving patients away from practitioners – appears to be the more valid concern.

In early spring, the pandemic’s first surge was accompanied by reports of approximately 40% and 60% drops in visits to EDs and ambulatory centers, respectively. Stories of acute stroke patients avoiding treatment began to appear in the press. Major U.S. cities saw noteworthy declines in 911 calls, indicating a hesitancy to be taken to a hospital. That COVID-19 has been accompanied by mass unemployment and subsequent loss of insurance complicates the notion that fear alone is keeping people from treatment. In other countries, it has been explicitly linked. Investigators in Singapore noted that coronaphobia played a role in reducing willingness to attend in-person visits among adolescents with eating disorders. Similarly, case reports in Israel suggest that coronaphobia has contributed to delays in diagnoses of common pediatric diseases.

There is also a concern, colloquially termed “reentry anxiety,” that mental health problems caused by the pandemic, the accompanying lockdown, self-isolation, and quarantine practices will prove alarmingly durable. Even after this challenging moment in history draws to a close, many people may face substantial stress in returning to the normal activities of life – social, professional, familial – once taken for granted.

“We are in the beginning phase of that now,” said Dr. Anand. “Lots of people are decompensating, getting depressed, and needing treatment. I think the longer it goes on for, the more difficult it will be.”

In the United States, that day may seem far away. Nonetheless, it is important to begin laying the therapeutic groundwork now, according to Dr. Brown.

“I am recommending unconventional therapies like meet-up groups, online forums,” he said. “Everything has shifted online, and so there are a lot of support groups that patients can participate to learn coping skills and really hear what other people are going through.”

Before reaching that stage, Dr. Brown recommends that clinicians first simply discuss such anxieties with their patients in order to normalize them.

“Realize that everyone essentially is going through some degree of this right now. The coronavirus pandemic is literally impacting every person on the face of the planet. Sometimes just pointing that out to people can really help,” he said.

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

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Listening to Mozart’s piano music improves epilepsy, according to a meta-analysis presented at the virtual congress of the European College of Neuropsychopharmacology.

The results of the meta-analysis of 12 published studies of the so-called Mozart Effect that met rigorous Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines demonstrate that listening to Mozart results in significant reductions in both epileptic seizure frequency and interictal epileptiform discharges (IED), compared with baseline.

The benefits were apparent during and after even a single listening session, although the effect was greater with regular daily listening sessions, according to Gianluca Sesso, MD, a resident in child and adolescent psychiatry at the University of Pisa (Italy.)

“Obviously other music may have similar effects, but it may be that Mozart’s sonatas have distinctive rhythmic structures which are particularly suited to working on epilepsy,” he speculated, adding that the mechanism involved in the Mozart Effect on brain systems remains unclear.

“The highly consistent results of our meta-analysis strongly suggest that music-based neurostimulation may improve the clinical outcome in epilepsy by reducing seizures and IED, and thus deserves to be included in the set of nonpharmacologic complementary approaches for treating epilepsy,” Dr. Sesso added.

Four studies examined the effects of listening to Mozart’s Sonata for Two Pianos in D, K.448, the most-studied piece of music as a treatment for epilepsy. The data documented a 31% reduction in seizure frequency and 28% decrease in IED during a single listen, and a 79% reduction in IED after long-term Mozart music therapy. Similarly, studies demonstrated that listening to a set of Mozart’s compositions resulted in a 36% reduction in IED during and 38% decrease after a single listen, while regular listening in a prolonged treatment period resulted in a 66% reduction in seizure frequency from baseline.

Several studies compared the benefits of listening to K. 488 with those accrued through listening to Piano Sonata No. 16 in C major, K. 545. There was no significant difference between the two, according to Dr. Sesso.

He reported having no financial conflicts regarding his meta-analysis, carried out free of commercial support.

The full details of the meta-analysis were recently published in Clinical Neurophysiology.

bjancin@mdedge.com

Listening to Mozart’s piano music improves epilepsy, according to a meta-analysis presented at the virtual congress of the European College of Neuropsychopharmacology.

The results of the meta-analysis of 12 published studies of the so-called Mozart Effect that met rigorous Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines demonstrate that listening to Mozart results in significant reductions in both epileptic seizure frequency and interictal epileptiform discharges (IED), compared with baseline.

The benefits were apparent during and after even a single listening session, although the effect was greater with regular daily listening sessions, according to Gianluca Sesso, MD, a resident in child and adolescent psychiatry at the University of Pisa (Italy.)

“Obviously other music may have similar effects, but it may be that Mozart’s sonatas have distinctive rhythmic structures which are particularly suited to working on epilepsy,” he speculated, adding that the mechanism involved in the Mozart Effect on brain systems remains unclear.

“The highly consistent results of our meta-analysis strongly suggest that music-based neurostimulation may improve the clinical outcome in epilepsy by reducing seizures and IED, and thus deserves to be included in the set of nonpharmacologic complementary approaches for treating epilepsy,” Dr. Sesso added.

Four studies examined the effects of listening to Mozart’s Sonata for Two Pianos in D, K.448, the most-studied piece of music as a treatment for epilepsy. The data documented a 31% reduction in seizure frequency and 28% decrease in IED during a single listen, and a 79% reduction in IED after long-term Mozart music therapy. Similarly, studies demonstrated that listening to a set of Mozart’s compositions resulted in a 36% reduction in IED during and 38% decrease after a single listen, while regular listening in a prolonged treatment period resulted in a 66% reduction in seizure frequency from baseline.

Several studies compared the benefits of listening to K. 488 with those accrued through listening to Piano Sonata No. 16 in C major, K. 545. There was no significant difference between the two, according to Dr. Sesso.

He reported having no financial conflicts regarding his meta-analysis, carried out free of commercial support.

The full details of the meta-analysis were recently published in Clinical Neurophysiology.

bjancin@mdedge.com

Listening to Mozart’s piano music improves epilepsy, according to a meta-analysis presented at the virtual congress of the European College of Neuropsychopharmacology.

The results of the meta-analysis of 12 published studies of the so-called Mozart Effect that met rigorous Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines demonstrate that listening to Mozart results in significant reductions in both epileptic seizure frequency and interictal epileptiform discharges (IED), compared with baseline.

The benefits were apparent during and after even a single listening session, although the effect was greater with regular daily listening sessions, according to Gianluca Sesso, MD, a resident in child and adolescent psychiatry at the University of Pisa (Italy.)

“Obviously other music may have similar effects, but it may be that Mozart’s sonatas have distinctive rhythmic structures which are particularly suited to working on epilepsy,” he speculated, adding that the mechanism involved in the Mozart Effect on brain systems remains unclear.

“The highly consistent results of our meta-analysis strongly suggest that music-based neurostimulation may improve the clinical outcome in epilepsy by reducing seizures and IED, and thus deserves to be included in the set of nonpharmacologic complementary approaches for treating epilepsy,” Dr. Sesso added.

Four studies examined the effects of listening to Mozart’s Sonata for Two Pianos in D, K.448, the most-studied piece of music as a treatment for epilepsy. The data documented a 31% reduction in seizure frequency and 28% decrease in IED during a single listen, and a 79% reduction in IED after long-term Mozart music therapy. Similarly, studies demonstrated that listening to a set of Mozart’s compositions resulted in a 36% reduction in IED during and 38% decrease after a single listen, while regular listening in a prolonged treatment period resulted in a 66% reduction in seizure frequency from baseline.

Several studies compared the benefits of listening to K. 488 with those accrued through listening to Piano Sonata No. 16 in C major, K. 545. There was no significant difference between the two, according to Dr. Sesso.

He reported having no financial conflicts regarding his meta-analysis, carried out free of commercial support.

The full details of the meta-analysis were recently published in Clinical Neurophysiology.

bjancin@mdedge.com

Among women with multiple sclerosis (MS), levels of serum neurofilament light (sNfL) are higher during pregnancy and the postpartum period. The increase in sNfL is independent of relapses, which suggests that patients have increased subclinical disease activity during this period, according to the researchers.

When the investigators controlled their data for exposure to disease-modifying therapy (DMT), the effect of pregnancy on sNfL was no longer evident. These data were presented said at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The results suggest that “sNfL may qualify as a sensitive and minimally invasive measure of disease activity in pregnancy,” said Özgür Yaldizli, MD, consultant neurologist at University Hospital Basel (Switzerland). “Strategies allowing the continuation of DMT during pregnancy may be warranted.”

MS preferentially affects women in their reproductive years, said Dr. Yaldizli. Almost one-third of women with MS become pregnant after they receive their diagnosis. A decrease in disease activity is typical in the third trimester, as is an increase in relapse frequency post partum.

DMTs reduce the risk of relapse, but have potential side effects for the woman and the fetus. Some DMTs are immunosuppressants, and they increase the risk of infection during pregnancy. Other DMTs may harm the development of the fetus, particularly if administered early during pregnancy.

“There is an urgent need to identify patients with high disease activity during pregnancy,” said Dr. Yaldizli. Increased levels of NfL, a specific biomarker of neuroaxonal injury, are associated with relapses, MRI activity, and disability worsening among patients with MS. Response to DMT is associated with decreased NfL levels. But few data about sNfL during pregnancy or post partum are available.
 

Relapses were associated with increased sNfL

Dr. Yaldizli and colleagues examined data from the Swiss MS Cohort Study to describe DMT use before, during, and after pregnancy. They also sought to assess sNfL as a marker of disease activity during and after pregnancy and to evaluate whether interrupting DMT because of pregnancy leads to increased sNfL levels.

Eligible participants had prospectively documented pregnancies, and Dr. Yaldizli’s group excluded pregnancies with early termination from their analysis. Serum samples were collected every 6 or 12 months and analyzed using the Simoa NF-light assay. The investigators used univariable and multivariable mixed-effects models to investigate associations between clinical characteristics and longitudinal sNfL levels in women before pregnancy, during pregnancy, and post partum.

Dr. Yaldizli and colleagues included 72 pregnancies in 63 patients with relapsing MS in their analysis. Nine patients had two pregnancies during follow-up. The population’s median age was 31.4 years, and median disease duration was 7.1 years. Median Expanded Disability Status Scale (EDSS) score at last visit before birth was 1.5. Median follow-up time was 6 years.

Most patients were treated with DMT before or during pregnancy. For most patients (39), fingolimod or natalizumab was the last DMT given before birth. Four patients did not use DMT before, during, or after pregnancy. In 14 pregnancies, the patient continued DMT for more than 6 months.

The univariable analysis showed that sNfL levels were 22% higher during pregnancy, compared with outside the pregnancy and postpartum period. The investigators recorded 29 relapses during the pregnancy and postpartum period. Relapses were more likely to occur during the first trimester and the first 3 months post partum. In the multivariable analysis, relapses that occurred within 120 days before serum sampling were associated with 98% higher levels of sNfL. In addition, sNfL was 7% higher for each step increase in EDSS and 13% higher during the pregnancy and postpartum period, compared with outside of that period.

When the investigators included DMT exposure at sampling time in the model, however, the pregnancy and postpartum period no longer had an effect on sNfL. The sNfL levels were 12% lower among patients exposed to DMT, compared with patients without DMT exposure.

Some DMTs, such as interferon-beta, are relatively safe during pregnancy, but the greater the medication’s efficacy, the more problematic it can be, said Dr. Yaldizi. “There are medications that are given, for example, every 6 months, like ocrelizumab. There are other medications that have to be taken daily. Probably the safest medications are those that are not given so often during pregnancy.”

Future research should examine the escalation therapies (i.e., the newer and more effective DMTs) during pregnancy in patients with MS, he added. “Not only in pregnancy, but also in general, we have to look for ways to measure disease activity in patients who switch therapy, who deescalate therapy.”
 

Pregnancy may not forestall disease activity

“The results of this study demonstrate that DMT withdrawal in the context of pregnancy can lead to subclinical disease re-emergence, as evidenced by increased sNfL levels in the DMT-free period,” said Vilija G. Jokubaitis, PhD, senior research fellow in the department of neuroscience at Monash University, Melbourne. Dr. Jokubaitis was not involved in the study.

“Interestingly, the median EDSS score in this cohort was quite low, demonstrating that, even in women with mild disease, pregnancy may not be sufficient to protect against ongoing MS activity.” Nevertheless, 28 of the 63 women were exposed to monoclonal antibody therapy, so it is unclear whether these women have mild disease or well-managed disease on DMT, she added.

“This study provides further evidence that pregnancy planning requires advanced planning, and that therapy continuation into pregnancy should be considered, particularly in women with moderate disease activity, to protect against disease reactivation,” said Dr. Jokubaitis.

The strengths of the study include its prospective design, the investigators’ ability to describe the various DMT exposures before and during pregnancy, and the multivariable mixed-effects modeling, she added. On the other hand, the results are at the group level, individual trajectories in sNfL level are not described, and the small sample size prevented the investigators from differentiating between the effects of various DMTs on sNfL outcomes. In addition, Dr. Yaldizli and colleagues did not take time off DMT into account in the models; they considered DMT exposure as a dichotomous variable.

“More work is needed to determine the therapeutic strategies that will give women with MS the greatest protection against disease reactivation in pregnancy and post partum, whilst also protecting fetal and neonatal outcomes,” said Dr. Jokubaitis. Group studies will enable researchers to identify trends, but neurologists ultimately need to provide individualized advice to their patients. “There is a need to look at [the effect of] DMT identity, timing, and duration of DMT withdrawal on fluctuation of sNfL levels, and how these relate to baseline disease severity,” Dr. Jokubaitis added. Furthermore, researchers must compare sNfL changes in pregnancy between patients with MS and healthy women in large cohorts.

The analysis by Dr. Yaldizli and colleagues was conducted without outside funding. The Swiss MS Cohort receives funding from the Swiss MS society, Biogen, Celgene, Sanofi, Merck, Novartis, Roche, and research associations such as the International Progressive MS Alliance and the Swiss National Science Foundation. Dr. Yaldizli received grants from ECTRIMS/MAGNIMS, the University of Basel, Pro Patient Stiftung, University Hospital Basel, Free Academy Basel, and the Swiss MS Society. He has received advisory board fees from Sanofi Genzyme, Biogen, Almirall, and Novartis. Dr. Jokubaitis has received conference travel support from Merck and Roche and speakers honoraria from Biogen and Roche. These relationships are not related to the current study. Dr. Jokubaitis receives research support from the Australian National Health and Medical Research Grant and MS Research Australia.

egreb@mdedge.com

Among women with multiple sclerosis (MS), levels of serum neurofilament light (sNfL) are higher during pregnancy and the postpartum period. The increase in sNfL is independent of relapses, which suggests that patients have increased subclinical disease activity during this period, according to the researchers.

When the investigators controlled their data for exposure to disease-modifying therapy (DMT), the effect of pregnancy on sNfL was no longer evident. These data were presented said at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The results suggest that “sNfL may qualify as a sensitive and minimally invasive measure of disease activity in pregnancy,” said Özgür Yaldizli, MD, consultant neurologist at University Hospital Basel (Switzerland). “Strategies allowing the continuation of DMT during pregnancy may be warranted.”

MS preferentially affects women in their reproductive years, said Dr. Yaldizli. Almost one-third of women with MS become pregnant after they receive their diagnosis. A decrease in disease activity is typical in the third trimester, as is an increase in relapse frequency post partum.

DMTs reduce the risk of relapse, but have potential side effects for the woman and the fetus. Some DMTs are immunosuppressants, and they increase the risk of infection during pregnancy. Other DMTs may harm the development of the fetus, particularly if administered early during pregnancy.

“There is an urgent need to identify patients with high disease activity during pregnancy,” said Dr. Yaldizli. Increased levels of NfL, a specific biomarker of neuroaxonal injury, are associated with relapses, MRI activity, and disability worsening among patients with MS. Response to DMT is associated with decreased NfL levels. But few data about sNfL during pregnancy or post partum are available.
 

Relapses were associated with increased sNfL

Dr. Yaldizli and colleagues examined data from the Swiss MS Cohort Study to describe DMT use before, during, and after pregnancy. They also sought to assess sNfL as a marker of disease activity during and after pregnancy and to evaluate whether interrupting DMT because of pregnancy leads to increased sNfL levels.

Eligible participants had prospectively documented pregnancies, and Dr. Yaldizli’s group excluded pregnancies with early termination from their analysis. Serum samples were collected every 6 or 12 months and analyzed using the Simoa NF-light assay. The investigators used univariable and multivariable mixed-effects models to investigate associations between clinical characteristics and longitudinal sNfL levels in women before pregnancy, during pregnancy, and post partum.

Dr. Yaldizli and colleagues included 72 pregnancies in 63 patients with relapsing MS in their analysis. Nine patients had two pregnancies during follow-up. The population’s median age was 31.4 years, and median disease duration was 7.1 years. Median Expanded Disability Status Scale (EDSS) score at last visit before birth was 1.5. Median follow-up time was 6 years.

Most patients were treated with DMT before or during pregnancy. For most patients (39), fingolimod or natalizumab was the last DMT given before birth. Four patients did not use DMT before, during, or after pregnancy. In 14 pregnancies, the patient continued DMT for more than 6 months.

The univariable analysis showed that sNfL levels were 22% higher during pregnancy, compared with outside the pregnancy and postpartum period. The investigators recorded 29 relapses during the pregnancy and postpartum period. Relapses were more likely to occur during the first trimester and the first 3 months post partum. In the multivariable analysis, relapses that occurred within 120 days before serum sampling were associated with 98% higher levels of sNfL. In addition, sNfL was 7% higher for each step increase in EDSS and 13% higher during the pregnancy and postpartum period, compared with outside of that period.

When the investigators included DMT exposure at sampling time in the model, however, the pregnancy and postpartum period no longer had an effect on sNfL. The sNfL levels were 12% lower among patients exposed to DMT, compared with patients without DMT exposure.

Some DMTs, such as interferon-beta, are relatively safe during pregnancy, but the greater the medication’s efficacy, the more problematic it can be, said Dr. Yaldizi. “There are medications that are given, for example, every 6 months, like ocrelizumab. There are other medications that have to be taken daily. Probably the safest medications are those that are not given so often during pregnancy.”

Future research should examine the escalation therapies (i.e., the newer and more effective DMTs) during pregnancy in patients with MS, he added. “Not only in pregnancy, but also in general, we have to look for ways to measure disease activity in patients who switch therapy, who deescalate therapy.”
 

Pregnancy may not forestall disease activity

“The results of this study demonstrate that DMT withdrawal in the context of pregnancy can lead to subclinical disease re-emergence, as evidenced by increased sNfL levels in the DMT-free period,” said Vilija G. Jokubaitis, PhD, senior research fellow in the department of neuroscience at Monash University, Melbourne. Dr. Jokubaitis was not involved in the study.

“Interestingly, the median EDSS score in this cohort was quite low, demonstrating that, even in women with mild disease, pregnancy may not be sufficient to protect against ongoing MS activity.” Nevertheless, 28 of the 63 women were exposed to monoclonal antibody therapy, so it is unclear whether these women have mild disease or well-managed disease on DMT, she added.

“This study provides further evidence that pregnancy planning requires advanced planning, and that therapy continuation into pregnancy should be considered, particularly in women with moderate disease activity, to protect against disease reactivation,” said Dr. Jokubaitis.

The strengths of the study include its prospective design, the investigators’ ability to describe the various DMT exposures before and during pregnancy, and the multivariable mixed-effects modeling, she added. On the other hand, the results are at the group level, individual trajectories in sNfL level are not described, and the small sample size prevented the investigators from differentiating between the effects of various DMTs on sNfL outcomes. In addition, Dr. Yaldizli and colleagues did not take time off DMT into account in the models; they considered DMT exposure as a dichotomous variable.

“More work is needed to determine the therapeutic strategies that will give women with MS the greatest protection against disease reactivation in pregnancy and post partum, whilst also protecting fetal and neonatal outcomes,” said Dr. Jokubaitis. Group studies will enable researchers to identify trends, but neurologists ultimately need to provide individualized advice to their patients. “There is a need to look at [the effect of] DMT identity, timing, and duration of DMT withdrawal on fluctuation of sNfL levels, and how these relate to baseline disease severity,” Dr. Jokubaitis added. Furthermore, researchers must compare sNfL changes in pregnancy between patients with MS and healthy women in large cohorts.

The analysis by Dr. Yaldizli and colleagues was conducted without outside funding. The Swiss MS Cohort receives funding from the Swiss MS society, Biogen, Celgene, Sanofi, Merck, Novartis, Roche, and research associations such as the International Progressive MS Alliance and the Swiss National Science Foundation. Dr. Yaldizli received grants from ECTRIMS/MAGNIMS, the University of Basel, Pro Patient Stiftung, University Hospital Basel, Free Academy Basel, and the Swiss MS Society. He has received advisory board fees from Sanofi Genzyme, Biogen, Almirall, and Novartis. Dr. Jokubaitis has received conference travel support from Merck and Roche and speakers honoraria from Biogen and Roche. These relationships are not related to the current study. Dr. Jokubaitis receives research support from the Australian National Health and Medical Research Grant and MS Research Australia.

egreb@mdedge.com

Among women with multiple sclerosis (MS), levels of serum neurofilament light (sNfL) are higher during pregnancy and the postpartum period. The increase in sNfL is independent of relapses, which suggests that patients have increased subclinical disease activity during this period, according to the researchers.

When the investigators controlled their data for exposure to disease-modifying therapy (DMT), the effect of pregnancy on sNfL was no longer evident. These data were presented said at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The results suggest that “sNfL may qualify as a sensitive and minimally invasive measure of disease activity in pregnancy,” said Özgür Yaldizli, MD, consultant neurologist at University Hospital Basel (Switzerland). “Strategies allowing the continuation of DMT during pregnancy may be warranted.”

MS preferentially affects women in their reproductive years, said Dr. Yaldizli. Almost one-third of women with MS become pregnant after they receive their diagnosis. A decrease in disease activity is typical in the third trimester, as is an increase in relapse frequency post partum.

DMTs reduce the risk of relapse, but have potential side effects for the woman and the fetus. Some DMTs are immunosuppressants, and they increase the risk of infection during pregnancy. Other DMTs may harm the development of the fetus, particularly if administered early during pregnancy.

“There is an urgent need to identify patients with high disease activity during pregnancy,” said Dr. Yaldizli. Increased levels of NfL, a specific biomarker of neuroaxonal injury, are associated with relapses, MRI activity, and disability worsening among patients with MS. Response to DMT is associated with decreased NfL levels. But few data about sNfL during pregnancy or post partum are available.
 

Relapses were associated with increased sNfL

Dr. Yaldizli and colleagues examined data from the Swiss MS Cohort Study to describe DMT use before, during, and after pregnancy. They also sought to assess sNfL as a marker of disease activity during and after pregnancy and to evaluate whether interrupting DMT because of pregnancy leads to increased sNfL levels.

Eligible participants had prospectively documented pregnancies, and Dr. Yaldizli’s group excluded pregnancies with early termination from their analysis. Serum samples were collected every 6 or 12 months and analyzed using the Simoa NF-light assay. The investigators used univariable and multivariable mixed-effects models to investigate associations between clinical characteristics and longitudinal sNfL levels in women before pregnancy, during pregnancy, and post partum.

Dr. Yaldizli and colleagues included 72 pregnancies in 63 patients with relapsing MS in their analysis. Nine patients had two pregnancies during follow-up. The population’s median age was 31.4 years, and median disease duration was 7.1 years. Median Expanded Disability Status Scale (EDSS) score at last visit before birth was 1.5. Median follow-up time was 6 years.

Most patients were treated with DMT before or during pregnancy. For most patients (39), fingolimod or natalizumab was the last DMT given before birth. Four patients did not use DMT before, during, or after pregnancy. In 14 pregnancies, the patient continued DMT for more than 6 months.

The univariable analysis showed that sNfL levels were 22% higher during pregnancy, compared with outside the pregnancy and postpartum period. The investigators recorded 29 relapses during the pregnancy and postpartum period. Relapses were more likely to occur during the first trimester and the first 3 months post partum. In the multivariable analysis, relapses that occurred within 120 days before serum sampling were associated with 98% higher levels of sNfL. In addition, sNfL was 7% higher for each step increase in EDSS and 13% higher during the pregnancy and postpartum period, compared with outside of that period.

When the investigators included DMT exposure at sampling time in the model, however, the pregnancy and postpartum period no longer had an effect on sNfL. The sNfL levels were 12% lower among patients exposed to DMT, compared with patients without DMT exposure.

Some DMTs, such as interferon-beta, are relatively safe during pregnancy, but the greater the medication’s efficacy, the more problematic it can be, said Dr. Yaldizi. “There are medications that are given, for example, every 6 months, like ocrelizumab. There are other medications that have to be taken daily. Probably the safest medications are those that are not given so often during pregnancy.”

Future research should examine the escalation therapies (i.e., the newer and more effective DMTs) during pregnancy in patients with MS, he added. “Not only in pregnancy, but also in general, we have to look for ways to measure disease activity in patients who switch therapy, who deescalate therapy.”
 

Pregnancy may not forestall disease activity

“The results of this study demonstrate that DMT withdrawal in the context of pregnancy can lead to subclinical disease re-emergence, as evidenced by increased sNfL levels in the DMT-free period,” said Vilija G. Jokubaitis, PhD, senior research fellow in the department of neuroscience at Monash University, Melbourne. Dr. Jokubaitis was not involved in the study.

“Interestingly, the median EDSS score in this cohort was quite low, demonstrating that, even in women with mild disease, pregnancy may not be sufficient to protect against ongoing MS activity.” Nevertheless, 28 of the 63 women were exposed to monoclonal antibody therapy, so it is unclear whether these women have mild disease or well-managed disease on DMT, she added.

“This study provides further evidence that pregnancy planning requires advanced planning, and that therapy continuation into pregnancy should be considered, particularly in women with moderate disease activity, to protect against disease reactivation,” said Dr. Jokubaitis.

The strengths of the study include its prospective design, the investigators’ ability to describe the various DMT exposures before and during pregnancy, and the multivariable mixed-effects modeling, she added. On the other hand, the results are at the group level, individual trajectories in sNfL level are not described, and the small sample size prevented the investigators from differentiating between the effects of various DMTs on sNfL outcomes. In addition, Dr. Yaldizli and colleagues did not take time off DMT into account in the models; they considered DMT exposure as a dichotomous variable.

“More work is needed to determine the therapeutic strategies that will give women with MS the greatest protection against disease reactivation in pregnancy and post partum, whilst also protecting fetal and neonatal outcomes,” said Dr. Jokubaitis. Group studies will enable researchers to identify trends, but neurologists ultimately need to provide individualized advice to their patients. “There is a need to look at [the effect of] DMT identity, timing, and duration of DMT withdrawal on fluctuation of sNfL levels, and how these relate to baseline disease severity,” Dr. Jokubaitis added. Furthermore, researchers must compare sNfL changes in pregnancy between patients with MS and healthy women in large cohorts.

The analysis by Dr. Yaldizli and colleagues was conducted without outside funding. The Swiss MS Cohort receives funding from the Swiss MS society, Biogen, Celgene, Sanofi, Merck, Novartis, Roche, and research associations such as the International Progressive MS Alliance and the Swiss National Science Foundation. Dr. Yaldizli received grants from ECTRIMS/MAGNIMS, the University of Basel, Pro Patient Stiftung, University Hospital Basel, Free Academy Basel, and the Swiss MS Society. He has received advisory board fees from Sanofi Genzyme, Biogen, Almirall, and Novartis. Dr. Jokubaitis has received conference travel support from Merck and Roche and speakers honoraria from Biogen and Roche. These relationships are not related to the current study. Dr. Jokubaitis receives research support from the Australian National Health and Medical Research Grant and MS Research Australia.

egreb@mdedge.com

The gap in suicide rates between rural and urban areas has widened since 2000 for both males and females, according to a recent report from the National Center for Health Statistics.

After remaining stable from 2000 to 2007, the suicide rate for rural males rose 34% from 2007 to 2018, versus 17% among urban males over the same period. Suicide rates for females were significantly lower than those of men, but the changes were larger. For rural females, the rate increased 91% from 2000 to 2018, compared with 51% for urban females, Kristen Pettrone, MD, MPH, and Sally C. Curtin, MA, said in an NCHS Data Brief.

For 2018, the last year with available data, the age-adjusted rates look like this: 21.5 per 100,000 population for urban males, 30.7 for rural males, 5.9 per 100,000 for urban females, and 8.0 for rural females. The overall rate for the United States was 14.2 per 100,000, with combined male/female rates of 13.4 in urban areas and 19.4 in rural areas, the researchers said.

Methods of suicide also varied by sex and urban-rural status. Firearms were the leading method for males in both rural and urban areas, but females split between firearms in rural areas and suffocation (including hangings) in urban areas, said Dr. Pettrone of the Centers for Disease Control and Prevention and Ms. Curtin of the NCHS.

Suffocation, however, was the fastest-growing method from 2000 to 2018, regardless of sex or location. Suffocation-related suicide rates more than quadrupled for rural females, and more than doubled for urban females and rural males, while rates rose 85% among males in urban areas, based on data from the National Vital Statistics System.

“Suicide has remained the 10th leading cause of death in the United States since 2008,” they wrote, and “sex and urban-rural disparities in methods of suicide may inform targeted suicide prevention strategies.”

rfranki@mdedge.com

SOURCE: Pettrone K, Curtin SC. 2020 Aug. NCHS Data Brief, No 373.

The gap in suicide rates between rural and urban areas has widened since 2000 for both males and females, according to a recent report from the National Center for Health Statistics.

After remaining stable from 2000 to 2007, the suicide rate for rural males rose 34% from 2007 to 2018, versus 17% among urban males over the same period. Suicide rates for females were significantly lower than those of men, but the changes were larger. For rural females, the rate increased 91% from 2000 to 2018, compared with 51% for urban females, Kristen Pettrone, MD, MPH, and Sally C. Curtin, MA, said in an NCHS Data Brief.

For 2018, the last year with available data, the age-adjusted rates look like this: 21.5 per 100,000 population for urban males, 30.7 for rural males, 5.9 per 100,000 for urban females, and 8.0 for rural females. The overall rate for the United States was 14.2 per 100,000, with combined male/female rates of 13.4 in urban areas and 19.4 in rural areas, the researchers said.

Methods of suicide also varied by sex and urban-rural status. Firearms were the leading method for males in both rural and urban areas, but females split between firearms in rural areas and suffocation (including hangings) in urban areas, said Dr. Pettrone of the Centers for Disease Control and Prevention and Ms. Curtin of the NCHS.

Suffocation, however, was the fastest-growing method from 2000 to 2018, regardless of sex or location. Suffocation-related suicide rates more than quadrupled for rural females, and more than doubled for urban females and rural males, while rates rose 85% among males in urban areas, based on data from the National Vital Statistics System.

“Suicide has remained the 10th leading cause of death in the United States since 2008,” they wrote, and “sex and urban-rural disparities in methods of suicide may inform targeted suicide prevention strategies.”

rfranki@mdedge.com

SOURCE: Pettrone K, Curtin SC. 2020 Aug. NCHS Data Brief, No 373.

The gap in suicide rates between rural and urban areas has widened since 2000 for both males and females, according to a recent report from the National Center for Health Statistics.

After remaining stable from 2000 to 2007, the suicide rate for rural males rose 34% from 2007 to 2018, versus 17% among urban males over the same period. Suicide rates for females were significantly lower than those of men, but the changes were larger. For rural females, the rate increased 91% from 2000 to 2018, compared with 51% for urban females, Kristen Pettrone, MD, MPH, and Sally C. Curtin, MA, said in an NCHS Data Brief.

For 2018, the last year with available data, the age-adjusted rates look like this: 21.5 per 100,000 population for urban males, 30.7 for rural males, 5.9 per 100,000 for urban females, and 8.0 for rural females. The overall rate for the United States was 14.2 per 100,000, with combined male/female rates of 13.4 in urban areas and 19.4 in rural areas, the researchers said.

Methods of suicide also varied by sex and urban-rural status. Firearms were the leading method for males in both rural and urban areas, but females split between firearms in rural areas and suffocation (including hangings) in urban areas, said Dr. Pettrone of the Centers for Disease Control and Prevention and Ms. Curtin of the NCHS.

Suffocation, however, was the fastest-growing method from 2000 to 2018, regardless of sex or location. Suffocation-related suicide rates more than quadrupled for rural females, and more than doubled for urban females and rural males, while rates rose 85% among males in urban areas, based on data from the National Vital Statistics System.

“Suicide has remained the 10th leading cause of death in the United States since 2008,” they wrote, and “sex and urban-rural disparities in methods of suicide may inform targeted suicide prevention strategies.”

rfranki@mdedge.com

SOURCE: Pettrone K, Curtin SC. 2020 Aug. NCHS Data Brief, No 373.

The author would like to make the following correction to the Editorial, originally published in the July issue of the Journal of Hospital Medicine 2020;15(7):447-448. DOI 10.12788/jhm.3468. In the third paragraph, MINS was described as an “umbrella term that can indicate either a myocardial infarction (MI) or nonischemic myocardial injury (NIMI).” This is not fully accurate: MINS is an umbrella term that can indicate either an MI or other myocardial injury due to ischemia. The correction to the paragraph is as follows, indicated in bold type:

In this journal issue, Cohn and colleagues summarize the current information around this phenomenon of myocardial injury after noncardiac surgery, or MINS.¹ Consistent with the literature, they define MINS as an acute rise and/or fall in troponin (above the assay’s upper limit of normal) at any point in the 30 days following noncardiac surgery. Importantly, MINS is an umbrella term that can indicate either an MI or other myocardial injury due to ischemia. An MI exists if there are clinical signs of ischemia and/or objective evidence of infarction on imaging.

The author would like to make the following correction to the Editorial, originally published in the July issue of the Journal of Hospital Medicine 2020;15(7):447-448. DOI 10.12788/jhm.3468. In the third paragraph, MINS was described as an “umbrella term that can indicate either a myocardial infarction (MI) or nonischemic myocardial injury (NIMI).” This is not fully accurate: MINS is an umbrella term that can indicate either an MI or other myocardial injury due to ischemia. The correction to the paragraph is as follows, indicated in bold type:

In this journal issue, Cohn and colleagues summarize the current information around this phenomenon of myocardial injury after noncardiac surgery, or MINS.¹ Consistent with the literature, they define MINS as an acute rise and/or fall in troponin (above the assay’s upper limit of normal) at any point in the 30 days following noncardiac surgery. Importantly, MINS is an umbrella term that can indicate either an MI or other myocardial injury due to ischemia. An MI exists if there are clinical signs of ischemia and/or objective evidence of infarction on imaging.

The author would like to make the following correction to the Editorial, originally published in the July issue of the Journal of Hospital Medicine 2020;15(7):447-448. DOI 10.12788/jhm.3468. In the third paragraph, MINS was described as an “umbrella term that can indicate either a myocardial infarction (MI) or nonischemic myocardial injury (NIMI).” This is not fully accurate: MINS is an umbrella term that can indicate either an MI or other myocardial injury due to ischemia. The correction to the paragraph is as follows, indicated in bold type:

In this journal issue, Cohn and colleagues summarize the current information around this phenomenon of myocardial injury after noncardiac surgery, or MINS.¹ Consistent with the literature, they define MINS as an acute rise and/or fall in troponin (above the assay’s upper limit of normal) at any point in the 30 days following noncardiac surgery. Importantly, MINS is an umbrella term that can indicate either an MI or other myocardial injury due to ischemia. An MI exists if there are clinical signs of ischemia and/or objective evidence of infarction on imaging.

When asked by friend or family “Which hospital did you go to?” or “Which doctor did you see?” most are likely to answer with a single institution or clinician. Yet for hospital stays the patient’s experience and outcomes are a product of many individuals and an entire system of care, so measuring performance at the group, or “team,” level is appropriate.

Assessing and managing performance of individuals in healthcare is also important. In this regard, though, healthcare may be more like assessing individual baseball players prior to the widespread adoption of detailed statistics, a transition to what is often referred to as sabermetrics (and popularized by the 2004 book Moneyball).¹ An individual player’s performance and future potential went from being assessed largely by the opinion of expert talent scouts to including, or even principally relying on, a wide array of measurements and statistics.

It sometimes seems healthcare has arrived at its “sabermetrics moment.” There is a rapidly growing set of measures for individual clinicians, and nearly every week, hospitalists will open a new report of their performance sent by a payer, a government agency, their own hospitals, or other organizations. But most of these metrics suffer from problems with attributing performance to a single clinician; for example, many or most metrics attribute performance to the attending at the time of a patient’s discharge according to the clinical record. Yet while clinical metrics (eg, administer beta-blocker when indicated, length of stay (LOS), readmissions), patient experience, financial metrics (eg, cost per case), and others are vital to understanding performance at an aggregate level such as a hospital or physician group, they are potentially confusing or even misleading when attributed entirely to the discharging provider. So healthcare leaders still tend to rely meaningfully on expert opinion—“talent scouts”—to identify high performers.

In this issue of the Journal of Hospital Medicine, Dow and colleagues have advanced our understanding of the current state of individual- rather than group-level hospitalist performance measurement.² This scoping review identified 43 studies published over the last 25 years reporting individual adult or pediatric hospitalist performance across one or more of the STEEEP framework domains of performance: Safe, Timely, Effective, Efficient, Equitable, Patient Centered.³

The most common domain assessed in the studies was Patient Centered (20 studies), and in descending order from there were Safe (16), Efficient (13), Timely (10), Effective (9). No studies reported individual hospitalist performance on Equitable care. This distribution of studied domains is likely a function of readily available data and processes for study more than level of interest or importance attached to each domain. Their research was not designed to assess the quality of each study, and some—or even many—might have weaknesses in both determining which clinicians met the definition of hospitalist and how performance was attributed to individuals. The authors appropriately conclude that “further defining and refining approaches to assess individual performance is necessary to ensure the highest quality.”

Their findings should help guide research priorities regarding measurement of individual hospitalist performance. Yet each hospitalist group and individual hospitalist still faces decisions about managing their own group and personal performance and must navigate without the benefit of research providing clear direction. Many hospitalist metrics are tracked and reported to meet regulatory requirements such as those from Centers for Medicare & Medicaid Services, financial metrics for the local hospital and hospitalist group, and for use as components of hospitalist compensation. (The biennial State of Hospital Medicine Report captures extensive data regarding the latter.⁴)

Many people and processes across an entire healthcare system influence performance on every metric, but it is useful and practical to attribute some metrics entirely to a single hospitalist provider, such as timely documentation and the time of day the discharge order is entered. And arguably, it is useful to attribute readmission rate entirely to the discharging provider—the last hospital provider who can influence readmission risk. But for most other metrics individual attribution is problematic or misleading and collective experience and expert opinion are helpful here. Two examples come to mind of relatively simple approaches that have gained some popularity in teasing out individual contribution to hospitalist performance.

One can estimate individual hospitalist contribution to patient LOS by calculating the ratio of current procedural terminology (CPT) codes for all follow-up services to all discharge codes. For each hospitalist in the group who cares for a similar population, those with the highest ratios likely manage patients in ways associated with longer LOS. It is relatively simple to use billing data to calculate the ratio, and some groups report it for all providers monthly.

Many metrics that aggregate performance across an entire hospital stay, such as patient experience surveys, can be apportioned to each hospitalist who had a billed encounter with the patient. For example, if a hospitalist has 4 of a patient’s 10 billed encounters within the same group, then 40% of the patient’s survey score could be attributed to that hospitalist. It’s still imperfect, but it’s likely more meaningful than attributing the entire survey result to only the discharging provider.

These approaches have value but still leave us unsatisfied and unable to assess performance as effectively as we would like. Advancements in measurement have been slow and incremental, but they are likely to accelerate with maturation of electronic health records paired with machine learning or artificial intelligence, wearable devices, and sensors in patient rooms, which collectively may make capturing a robust set of metrics trivially easy (and raise questions regarding privacy and so forth). For example, it is already possible to capture via a smart speaker all conversations between patient, loved ones, and clinician.⁵ Imagine you are presented with a word cloud summary of all conversations you had with all patients over a year. Did you use empathy words often enough? How reliably did you address all appropriate discharge-related topics?

As performance metrics become more numerous and ubiquitous, the challenge will be to ensure they accurately capture what they appear to measure, are appropriately attributed to individuals or groups, and provide insights into important domains of performance. Significant opportunity for improvement remains.

Dr Nelson has no conflict of interest to disclose.

When asked by friend or family “Which hospital did you go to?” or “Which doctor did you see?” most are likely to answer with a single institution or clinician. Yet for hospital stays the patient’s experience and outcomes are a product of many individuals and an entire system of care, so measuring performance at the group, or “team,” level is appropriate.

Assessing and managing performance of individuals in healthcare is also important. In this regard, though, healthcare may be more like assessing individual baseball players prior to the widespread adoption of detailed statistics, a transition to what is often referred to as sabermetrics (and popularized by the 2004 book Moneyball).¹ An individual player’s performance and future potential went from being assessed largely by the opinion of expert talent scouts to including, or even principally relying on, a wide array of measurements and statistics.

It sometimes seems healthcare has arrived at its “sabermetrics moment.” There is a rapidly growing set of measures for individual clinicians, and nearly every week, hospitalists will open a new report of their performance sent by a payer, a government agency, their own hospitals, or other organizations. But most of these metrics suffer from problems with attributing performance to a single clinician; for example, many or most metrics attribute performance to the attending at the time of a patient’s discharge according to the clinical record. Yet while clinical metrics (eg, administer beta-blocker when indicated, length of stay (LOS), readmissions), patient experience, financial metrics (eg, cost per case), and others are vital to understanding performance at an aggregate level such as a hospital or physician group, they are potentially confusing or even misleading when attributed entirely to the discharging provider. So healthcare leaders still tend to rely meaningfully on expert opinion—“talent scouts”—to identify high performers.

In this issue of the Journal of Hospital Medicine, Dow and colleagues have advanced our understanding of the current state of individual- rather than group-level hospitalist performance measurement.² This scoping review identified 43 studies published over the last 25 years reporting individual adult or pediatric hospitalist performance across one or more of the STEEEP framework domains of performance: Safe, Timely, Effective, Efficient, Equitable, Patient Centered.³

The most common domain assessed in the studies was Patient Centered (20 studies), and in descending order from there were Safe (16), Efficient (13), Timely (10), Effective (9). No studies reported individual hospitalist performance on Equitable care. This distribution of studied domains is likely a function of readily available data and processes for study more than level of interest or importance attached to each domain. Their research was not designed to assess the quality of each study, and some—or even many—might have weaknesses in both determining which clinicians met the definition of hospitalist and how performance was attributed to individuals. The authors appropriately conclude that “further defining and refining approaches to assess individual performance is necessary to ensure the highest quality.”

Their findings should help guide research priorities regarding measurement of individual hospitalist performance. Yet each hospitalist group and individual hospitalist still faces decisions about managing their own group and personal performance and must navigate without the benefit of research providing clear direction. Many hospitalist metrics are tracked and reported to meet regulatory requirements such as those from Centers for Medicare & Medicaid Services, financial metrics for the local hospital and hospitalist group, and for use as components of hospitalist compensation. (The biennial State of Hospital Medicine Report captures extensive data regarding the latter.⁴)

Many people and processes across an entire healthcare system influence performance on every metric, but it is useful and practical to attribute some metrics entirely to a single hospitalist provider, such as timely documentation and the time of day the discharge order is entered. And arguably, it is useful to attribute readmission rate entirely to the discharging provider—the last hospital provider who can influence readmission risk. But for most other metrics individual attribution is problematic or misleading and collective experience and expert opinion are helpful here. Two examples come to mind of relatively simple approaches that have gained some popularity in teasing out individual contribution to hospitalist performance.

One can estimate individual hospitalist contribution to patient LOS by calculating the ratio of current procedural terminology (CPT) codes for all follow-up services to all discharge codes. For each hospitalist in the group who cares for a similar population, those with the highest ratios likely manage patients in ways associated with longer LOS. It is relatively simple to use billing data to calculate the ratio, and some groups report it for all providers monthly.

Many metrics that aggregate performance across an entire hospital stay, such as patient experience surveys, can be apportioned to each hospitalist who had a billed encounter with the patient. For example, if a hospitalist has 4 of a patient’s 10 billed encounters within the same group, then 40% of the patient’s survey score could be attributed to that hospitalist. It’s still imperfect, but it’s likely more meaningful than attributing the entire survey result to only the discharging provider.

These approaches have value but still leave us unsatisfied and unable to assess performance as effectively as we would like. Advancements in measurement have been slow and incremental, but they are likely to accelerate with maturation of electronic health records paired with machine learning or artificial intelligence, wearable devices, and sensors in patient rooms, which collectively may make capturing a robust set of metrics trivially easy (and raise questions regarding privacy and so forth). For example, it is already possible to capture via a smart speaker all conversations between patient, loved ones, and clinician.⁵ Imagine you are presented with a word cloud summary of all conversations you had with all patients over a year. Did you use empathy words often enough? How reliably did you address all appropriate discharge-related topics?

As performance metrics become more numerous and ubiquitous, the challenge will be to ensure they accurately capture what they appear to measure, are appropriately attributed to individuals or groups, and provide insights into important domains of performance. Significant opportunity for improvement remains.

Dr Nelson has no conflict of interest to disclose.

When asked by friend or family “Which hospital did you go to?” or “Which doctor did you see?” most are likely to answer with a single institution or clinician. Yet for hospital stays the patient’s experience and outcomes are a product of many individuals and an entire system of care, so measuring performance at the group, or “team,” level is appropriate.

Assessing and managing performance of individuals in healthcare is also important. In this regard, though, healthcare may be more like assessing individual baseball players prior to the widespread adoption of detailed statistics, a transition to what is often referred to as sabermetrics (and popularized by the 2004 book Moneyball).¹ An individual player’s performance and future potential went from being assessed largely by the opinion of expert talent scouts to including, or even principally relying on, a wide array of measurements and statistics.

It sometimes seems healthcare has arrived at its “sabermetrics moment.” There is a rapidly growing set of measures for individual clinicians, and nearly every week, hospitalists will open a new report of their performance sent by a payer, a government agency, their own hospitals, or other organizations. But most of these metrics suffer from problems with attributing performance to a single clinician; for example, many or most metrics attribute performance to the attending at the time of a patient’s discharge according to the clinical record. Yet while clinical metrics (eg, administer beta-blocker when indicated, length of stay (LOS), readmissions), patient experience, financial metrics (eg, cost per case), and others are vital to understanding performance at an aggregate level such as a hospital or physician group, they are potentially confusing or even misleading when attributed entirely to the discharging provider. So healthcare leaders still tend to rely meaningfully on expert opinion—“talent scouts”—to identify high performers.

In this issue of the Journal of Hospital Medicine, Dow and colleagues have advanced our understanding of the current state of individual- rather than group-level hospitalist performance measurement.² This scoping review identified 43 studies published over the last 25 years reporting individual adult or pediatric hospitalist performance across one or more of the STEEEP framework domains of performance: Safe, Timely, Effective, Efficient, Equitable, Patient Centered.³

The most common domain assessed in the studies was Patient Centered (20 studies), and in descending order from there were Safe (16), Efficient (13), Timely (10), Effective (9). No studies reported individual hospitalist performance on Equitable care. This distribution of studied domains is likely a function of readily available data and processes for study more than level of interest or importance attached to each domain. Their research was not designed to assess the quality of each study, and some—or even many—might have weaknesses in both determining which clinicians met the definition of hospitalist and how performance was attributed to individuals. The authors appropriately conclude that “further defining and refining approaches to assess individual performance is necessary to ensure the highest quality.”

Their findings should help guide research priorities regarding measurement of individual hospitalist performance. Yet each hospitalist group and individual hospitalist still faces decisions about managing their own group and personal performance and must navigate without the benefit of research providing clear direction. Many hospitalist metrics are tracked and reported to meet regulatory requirements such as those from Centers for Medicare & Medicaid Services, financial metrics for the local hospital and hospitalist group, and for use as components of hospitalist compensation. (The biennial State of Hospital Medicine Report captures extensive data regarding the latter.⁴)

Many people and processes across an entire healthcare system influence performance on every metric, but it is useful and practical to attribute some metrics entirely to a single hospitalist provider, such as timely documentation and the time of day the discharge order is entered. And arguably, it is useful to attribute readmission rate entirely to the discharging provider—the last hospital provider who can influence readmission risk. But for most other metrics individual attribution is problematic or misleading and collective experience and expert opinion are helpful here. Two examples come to mind of relatively simple approaches that have gained some popularity in teasing out individual contribution to hospitalist performance.

One can estimate individual hospitalist contribution to patient LOS by calculating the ratio of current procedural terminology (CPT) codes for all follow-up services to all discharge codes. For each hospitalist in the group who cares for a similar population, those with the highest ratios likely manage patients in ways associated with longer LOS. It is relatively simple to use billing data to calculate the ratio, and some groups report it for all providers monthly.

Many metrics that aggregate performance across an entire hospital stay, such as patient experience surveys, can be apportioned to each hospitalist who had a billed encounter with the patient. For example, if a hospitalist has 4 of a patient’s 10 billed encounters within the same group, then 40% of the patient’s survey score could be attributed to that hospitalist. It’s still imperfect, but it’s likely more meaningful than attributing the entire survey result to only the discharging provider.

These approaches have value but still leave us unsatisfied and unable to assess performance as effectively as we would like. Advancements in measurement have been slow and incremental, but they are likely to accelerate with maturation of electronic health records paired with machine learning or artificial intelligence, wearable devices, and sensors in patient rooms, which collectively may make capturing a robust set of metrics trivially easy (and raise questions regarding privacy and so forth). For example, it is already possible to capture via a smart speaker all conversations between patient, loved ones, and clinician.⁵ Imagine you are presented with a word cloud summary of all conversations you had with all patients over a year. Did you use empathy words often enough? How reliably did you address all appropriate discharge-related topics?

As performance metrics become more numerous and ubiquitous, the challenge will be to ensure they accurately capture what they appear to measure, are appropriately attributed to individuals or groups, and provide insights into important domains of performance. Significant opportunity for improvement remains.

Dr Nelson has no conflict of interest to disclose.

Still in its infancy, the Hospital Compare overall hospital quality star rating program introduced by the Centers for Medicare & Medicaid Services (CMS) has generated intense industry debate. Individual health systems are microcosms of the challenges of ratings and measurement design. Sibley Memorial Hospital, a member of Johns Hopkins Medicine, is a well-run, 288-bed, community hospital located in a wealthy section of northwest District of Columbia with a five-star rating. In contrast, its academic partner, the Johns Hopkins Hospital, a 1,162-bed hospital with a century-long history of innovation situated in an impoverished Baltimore, Maryland, neighborhood, received a three-star rating.

Hospital ratings are the product of an industry in transition: As care delivery has shifted from an individual provider-driven industry to an increasingly scaled systems enterprise, policymakers implemented regulatory standards targeting quality measurement. Subsequent to the National Academy of Medicine’s 1999 report To Err is Human, policy efforts brought public reporting of quality ratings to multiple market segments, including dialysis facilities (2001), nursing homes (2003), Medicare Advantage plans (2007), and physicians (2015). The hospital industry was no exception, and in 2016—with much controversy¹—CMS launched the hospital star ratings program.

CMS Star Ratings for hospitals are based on seven measure groups: mortality, safety, readmission, patient experience, effectiveness, timeliness, and efficient use of medical imaging. Both industry and researchers have decried the challenges of star ratings, noting that hospitals with a narrower scope of services are more likely to receive higher ratings.² Measure groupings may be further flawed as shown by recent work demonstrating that larger, safety net, or academic hospitals, as well as hospitals offering transplant services, have higher readmission rates,³ which may be caused by differences in patient complexity. Other research has demonstrated that overall quality ratings inappropriately pool all hospitals together, when it may be fairer to initially categorize hospitals and then score them.⁴

It is within this maelstrom of debate that, in this month’s issue of the Journal of Hospital Medicine, Shi and colleagues explore the relationship between hospital star ratings and the socioeconomic features of the surrounding communities.⁵ Conducting their analysis by linking multiple reputable government and industry sources, Shi and colleagues found that counties with higher education attainment and a lower proportion of dual Medicare-Medicaid–eligible populations had higher hospital star ratings. Furthermore, a county’s minority population percentage negatively correlated with hospital ratings. Validating the experience of many rural hospital executives—who frequently experience financial challenges—Shi and colleagues noted that rural hospitals were less likely to receive five-star ratings.

Do these findings reflect a true disparity and lack of access to high-quality hospitals, or are they artifactual—secondary to a flawed construct of hospital quality measurement? Many lower-ranking hospitals are urban academic centers frequently providing services not offered at their five-star community counterparts, such as neurosurgery, comprehensive cancer care, and organ transplants, while simultaneously serving as safety net hospitals, research institutions, trauma centers, and national referral centers.

Sociodemographics factor significantly in self-care management for hospital aftercare. Health literacy, access to primary and behavioral healthcare, and transportation all affect star indicators. Recent work⁶ demonstrated that comprehensive investments in transitional care strategies and the social determinants of health were ineffective at reducing readmissions, which suggests that high readmission rates for hospitals in impoverished areas are not only common, but also may not accurately reflect hospital quality and local investment.

Patient experience is also complicating, with research demonstrating that patient perceptions vary significantly by education, age, primary language, ethnicity, and overall health. For example, one-third of average-ranked hospitals would have rankings vary by at least 18 percentile points when evaluated by Spanish-speaking patients. Star ratings fail to capture and communicate this granularity.⁷

More concerning is that star ratings inherently assume that hospital performance is being compared across the same tasks, regardless of patient characteristics, local resources, or the scope of services provided, the latter of which may vary between hospitals. For example, communication may differ in both complexity and time intensity: Explaining an antibiotic to the uncomplicated patient with pneumonia differs from prescribing an antibiotic to a patient who is legally blind from optic neuritis, walks with a cane because of multiple sclerosis, and has 24 other prescription medications. Similar challenges exist for differences in local neighborhood resources and for facilities with differing service scope.

Although one strategy to handle these “disparities” in star ratings might be to risk-adjust for social determinants of health, patients may be better served by first rethinking how star ratings are constructed. Clustering hospitals by scope of services provided and geographic region prior to determining star ratings would provide consumers with meaningful information by helping patients compare and make choices among either local or regional hospitals; national quality rankings are unhelpful for patients.

Arguably one of the most complex and person-dependent service enterprises, care delivery presents unique challenges for evaluation of customer experience and medical quality. Hospital star ratings are no exception: We must rethink their construction so they can be more meaningful for both patients and physicians.

The authors would like to acknowledge Daniel J Brotman, MD, for his editorial advice and input.

Dr Miller reported consulting for the Federal Trade Commission and serving as a member of the Centers for Medicare & Medicaid Services Medicare Evidence Development Coverage Advisory Committee. Drs Siddiqui and Deutschendorf have nothing to disclose.

Still in its infancy, the Hospital Compare overall hospital quality star rating program introduced by the Centers for Medicare & Medicaid Services (CMS) has generated intense industry debate. Individual health systems are microcosms of the challenges of ratings and measurement design. Sibley Memorial Hospital, a member of Johns Hopkins Medicine, is a well-run, 288-bed, community hospital located in a wealthy section of northwest District of Columbia with a five-star rating. In contrast, its academic partner, the Johns Hopkins Hospital, a 1,162-bed hospital with a century-long history of innovation situated in an impoverished Baltimore, Maryland, neighborhood, received a three-star rating.

Hospital ratings are the product of an industry in transition: As care delivery has shifted from an individual provider-driven industry to an increasingly scaled systems enterprise, policymakers implemented regulatory standards targeting quality measurement. Subsequent to the National Academy of Medicine’s 1999 report To Err is Human, policy efforts brought public reporting of quality ratings to multiple market segments, including dialysis facilities (2001), nursing homes (2003), Medicare Advantage plans (2007), and physicians (2015). The hospital industry was no exception, and in 2016—with much controversy¹—CMS launched the hospital star ratings program.

CMS Star Ratings for hospitals are based on seven measure groups: mortality, safety, readmission, patient experience, effectiveness, timeliness, and efficient use of medical imaging. Both industry and researchers have decried the challenges of star ratings, noting that hospitals with a narrower scope of services are more likely to receive higher ratings.² Measure groupings may be further flawed as shown by recent work demonstrating that larger, safety net, or academic hospitals, as well as hospitals offering transplant services, have higher readmission rates,³ which may be caused by differences in patient complexity. Other research has demonstrated that overall quality ratings inappropriately pool all hospitals together, when it may be fairer to initially categorize hospitals and then score them.⁴

It is within this maelstrom of debate that, in this month’s issue of the Journal of Hospital Medicine, Shi and colleagues explore the relationship between hospital star ratings and the socioeconomic features of the surrounding communities.⁵ Conducting their analysis by linking multiple reputable government and industry sources, Shi and colleagues found that counties with higher education attainment and a lower proportion of dual Medicare-Medicaid–eligible populations had higher hospital star ratings. Furthermore, a county’s minority population percentage negatively correlated with hospital ratings. Validating the experience of many rural hospital executives—who frequently experience financial challenges—Shi and colleagues noted that rural hospitals were less likely to receive five-star ratings.

Do these findings reflect a true disparity and lack of access to high-quality hospitals, or are they artifactual—secondary to a flawed construct of hospital quality measurement? Many lower-ranking hospitals are urban academic centers frequently providing services not offered at their five-star community counterparts, such as neurosurgery, comprehensive cancer care, and organ transplants, while simultaneously serving as safety net hospitals, research institutions, trauma centers, and national referral centers.

Sociodemographics factor significantly in self-care management for hospital aftercare. Health literacy, access to primary and behavioral healthcare, and transportation all affect star indicators. Recent work⁶ demonstrated that comprehensive investments in transitional care strategies and the social determinants of health were ineffective at reducing readmissions, which suggests that high readmission rates for hospitals in impoverished areas are not only common, but also may not accurately reflect hospital quality and local investment.

Patient experience is also complicating, with research demonstrating that patient perceptions vary significantly by education, age, primary language, ethnicity, and overall health. For example, one-third of average-ranked hospitals would have rankings vary by at least 18 percentile points when evaluated by Spanish-speaking patients. Star ratings fail to capture and communicate this granularity.⁷

More concerning is that star ratings inherently assume that hospital performance is being compared across the same tasks, regardless of patient characteristics, local resources, or the scope of services provided, the latter of which may vary between hospitals. For example, communication may differ in both complexity and time intensity: Explaining an antibiotic to the uncomplicated patient with pneumonia differs from prescribing an antibiotic to a patient who is legally blind from optic neuritis, walks with a cane because of multiple sclerosis, and has 24 other prescription medications. Similar challenges exist for differences in local neighborhood resources and for facilities with differing service scope.

Although one strategy to handle these “disparities” in star ratings might be to risk-adjust for social determinants of health, patients may be better served by first rethinking how star ratings are constructed. Clustering hospitals by scope of services provided and geographic region prior to determining star ratings would provide consumers with meaningful information by helping patients compare and make choices among either local or regional hospitals; national quality rankings are unhelpful for patients.

Arguably one of the most complex and person-dependent service enterprises, care delivery presents unique challenges for evaluation of customer experience and medical quality. Hospital star ratings are no exception: We must rethink their construction so they can be more meaningful for both patients and physicians.

The authors would like to acknowledge Daniel J Brotman, MD, for his editorial advice and input.

Dr Miller reported consulting for the Federal Trade Commission and serving as a member of the Centers for Medicare & Medicaid Services Medicare Evidence Development Coverage Advisory Committee. Drs Siddiqui and Deutschendorf have nothing to disclose.

Still in its infancy, the Hospital Compare overall hospital quality star rating program introduced by the Centers for Medicare & Medicaid Services (CMS) has generated intense industry debate. Individual health systems are microcosms of the challenges of ratings and measurement design. Sibley Memorial Hospital, a member of Johns Hopkins Medicine, is a well-run, 288-bed, community hospital located in a wealthy section of northwest District of Columbia with a five-star rating. In contrast, its academic partner, the Johns Hopkins Hospital, a 1,162-bed hospital with a century-long history of innovation situated in an impoverished Baltimore, Maryland, neighborhood, received a three-star rating.

Hospital ratings are the product of an industry in transition: As care delivery has shifted from an individual provider-driven industry to an increasingly scaled systems enterprise, policymakers implemented regulatory standards targeting quality measurement. Subsequent to the National Academy of Medicine’s 1999 report To Err is Human, policy efforts brought public reporting of quality ratings to multiple market segments, including dialysis facilities (2001), nursing homes (2003), Medicare Advantage plans (2007), and physicians (2015). The hospital industry was no exception, and in 2016—with much controversy¹—CMS launched the hospital star ratings program.

CMS Star Ratings for hospitals are based on seven measure groups: mortality, safety, readmission, patient experience, effectiveness, timeliness, and efficient use of medical imaging. Both industry and researchers have decried the challenges of star ratings, noting that hospitals with a narrower scope of services are more likely to receive higher ratings.² Measure groupings may be further flawed as shown by recent work demonstrating that larger, safety net, or academic hospitals, as well as hospitals offering transplant services, have higher readmission rates,³ which may be caused by differences in patient complexity. Other research has demonstrated that overall quality ratings inappropriately pool all hospitals together, when it may be fairer to initially categorize hospitals and then score them.⁴

It is within this maelstrom of debate that, in this month’s issue of the Journal of Hospital Medicine, Shi and colleagues explore the relationship between hospital star ratings and the socioeconomic features of the surrounding communities.⁵ Conducting their analysis by linking multiple reputable government and industry sources, Shi and colleagues found that counties with higher education attainment and a lower proportion of dual Medicare-Medicaid–eligible populations had higher hospital star ratings. Furthermore, a county’s minority population percentage negatively correlated with hospital ratings. Validating the experience of many rural hospital executives—who frequently experience financial challenges—Shi and colleagues noted that rural hospitals were less likely to receive five-star ratings.

Do these findings reflect a true disparity and lack of access to high-quality hospitals, or are they artifactual—secondary to a flawed construct of hospital quality measurement? Many lower-ranking hospitals are urban academic centers frequently providing services not offered at their five-star community counterparts, such as neurosurgery, comprehensive cancer care, and organ transplants, while simultaneously serving as safety net hospitals, research institutions, trauma centers, and national referral centers.

Sociodemographics factor significantly in self-care management for hospital aftercare. Health literacy, access to primary and behavioral healthcare, and transportation all affect star indicators. Recent work⁶ demonstrated that comprehensive investments in transitional care strategies and the social determinants of health were ineffective at reducing readmissions, which suggests that high readmission rates for hospitals in impoverished areas are not only common, but also may not accurately reflect hospital quality and local investment.

Patient experience is also complicating, with research demonstrating that patient perceptions vary significantly by education, age, primary language, ethnicity, and overall health. For example, one-third of average-ranked hospitals would have rankings vary by at least 18 percentile points when evaluated by Spanish-speaking patients. Star ratings fail to capture and communicate this granularity.⁷

More concerning is that star ratings inherently assume that hospital performance is being compared across the same tasks, regardless of patient characteristics, local resources, or the scope of services provided, the latter of which may vary between hospitals. For example, communication may differ in both complexity and time intensity: Explaining an antibiotic to the uncomplicated patient with pneumonia differs from prescribing an antibiotic to a patient who is legally blind from optic neuritis, walks with a cane because of multiple sclerosis, and has 24 other prescription medications. Similar challenges exist for differences in local neighborhood resources and for facilities with differing service scope.

Although one strategy to handle these “disparities” in star ratings might be to risk-adjust for social determinants of health, patients may be better served by first rethinking how star ratings are constructed. Clustering hospitals by scope of services provided and geographic region prior to determining star ratings would provide consumers with meaningful information by helping patients compare and make choices among either local or regional hospitals; national quality rankings are unhelpful for patients.

Arguably one of the most complex and person-dependent service enterprises, care delivery presents unique challenges for evaluation of customer experience and medical quality. Hospital star ratings are no exception: We must rethink their construction so they can be more meaningful for both patients and physicians.

The authors would like to acknowledge Daniel J Brotman, MD, for his editorial advice and input.

Dr Miller reported consulting for the Federal Trade Commission and serving as a member of the Centers for Medicare & Medicaid Services Medicare Evidence Development Coverage Advisory Committee. Drs Siddiqui and Deutschendorf have nothing to disclose.

“In the end, we will remember not the words of our enemies, but the silence of our friends.”

—Martin Luther King, Jr.

"Code Blue, Emergency Department Code Team to PACU.” A female senior resident dons her personal protective equipment and assembles her team. An enthusiastic male junior resident asks if he can accompany her, and off they go. They encounter a frantic scene in the post-anesthesia care unit (PACU). Before the senior resident can lead the rapid response, a PACU nurse addresses the junior resident: “You are leading the code, correct? What medications would you like?”

“Microaggressions” are subtle, commonplace exchanges that—whether intentional or unintentional—communicate disparaging messages to members of marginalized groups.¹ These groups often include women, members of racial/ethnic groups that are underrepresented in medicine, and lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals. Although an individual may not intend to cause harm, their words may still negatively impact the receiving party, who regularly experiences differential treatment based on sex, race, ethnicity, or other social identities. The effects of microaggressions extend beyond personal offense to include anxiety, depression, and even hypertension.^1,2

Addressing microaggressions can be challenging. Given that the recipients of microaggressions are often burdened with responding to them, it is important for bystanders to be empowered to respond as well. A bystander witnesses and recognizes the microaggression and can address it. Based on the work of Sue et al,³ we suggest that bystanders adopt the following strategies:

• Make the “invisible” visible. Many people do not perceive their actions as biased or prejudiced. It is therefore important to bring the implicit bias to the forefront by asking for clarification, naming the implication, or challenging the stereotype.
• Disarm the microaggression. Don’t be afraid to stop, deflect, disagree, or challenge what was said or done, thereby highlighting its potentially harmful impact. Another option is to interrupt the comment as it’s being said and redirect the conversation.
• Educate the speaker. Create a nonpunitive discussion by appealing to common values, promoting empathy, and increasing awareness of societal benefits. The speaker may become defensive and emphasize that their intent was not to cause harm. You must emphasize that, regardless of intent, the impact was hurtful. You may refocus the discussion with a simple statement such as, “I know you meant well, and…”
• Seek external support when needed. Addressing microaggressions can be emotionally taxing. Don’t be afraid to utilize community services, find a support group, or seek advice from professionals.

By virtue of being a neutral third party, bystanders who intervene may have greater success at explaining the impact of the microaggression. In doing so, the bystander also relieves the recipient of the microaggression of a burdensome response. In the above example, another provider in the PACU might pull the nurse aside later and say, “When you asked the junior resident if he was leading the code, you unintentionally indicated that he was the most experienced, which made it more challenging for the female senior resident to lead the response.” In this way, the “invisible” implication of the nurse’s words—that the male resident was the most knowledgeable physician in the room—is made visible, and the female resident is relieved of responding.

Microaggressions do not occur in a vacuum; context matters. Before employing these strategies, consider when, where, and how you address microaggressions. These strategies validate and support those on the receiving end of microaggressions, and thus counteract their deleterious effects. The onus is on us: we must not be silent.

The authors have nothing to disclose.

“In the end, we will remember not the words of our enemies, but the silence of our friends.”

—Martin Luther King, Jr.

"Code Blue, Emergency Department Code Team to PACU.” A female senior resident dons her personal protective equipment and assembles her team. An enthusiastic male junior resident asks if he can accompany her, and off they go. They encounter a frantic scene in the post-anesthesia care unit (PACU). Before the senior resident can lead the rapid response, a PACU nurse addresses the junior resident: “You are leading the code, correct? What medications would you like?”

“Microaggressions” are subtle, commonplace exchanges that—whether intentional or unintentional—communicate disparaging messages to members of marginalized groups.¹ These groups often include women, members of racial/ethnic groups that are underrepresented in medicine, and lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals. Although an individual may not intend to cause harm, their words may still negatively impact the receiving party, who regularly experiences differential treatment based on sex, race, ethnicity, or other social identities. The effects of microaggressions extend beyond personal offense to include anxiety, depression, and even hypertension.^1,2

Addressing microaggressions can be challenging. Given that the recipients of microaggressions are often burdened with responding to them, it is important for bystanders to be empowered to respond as well. A bystander witnesses and recognizes the microaggression and can address it. Based on the work of Sue et al,³ we suggest that bystanders adopt the following strategies:

• Make the “invisible” visible. Many people do not perceive their actions as biased or prejudiced. It is therefore important to bring the implicit bias to the forefront by asking for clarification, naming the implication, or challenging the stereotype.
• Disarm the microaggression. Don’t be afraid to stop, deflect, disagree, or challenge what was said or done, thereby highlighting its potentially harmful impact. Another option is to interrupt the comment as it’s being said and redirect the conversation.
• Educate the speaker. Create a nonpunitive discussion by appealing to common values, promoting empathy, and increasing awareness of societal benefits. The speaker may become defensive and emphasize that their intent was not to cause harm. You must emphasize that, regardless of intent, the impact was hurtful. You may refocus the discussion with a simple statement such as, “I know you meant well, and…”
• Seek external support when needed. Addressing microaggressions can be emotionally taxing. Don’t be afraid to utilize community services, find a support group, or seek advice from professionals.

By virtue of being a neutral third party, bystanders who intervene may have greater success at explaining the impact of the microaggression. In doing so, the bystander also relieves the recipient of the microaggression of a burdensome response. In the above example, another provider in the PACU might pull the nurse aside later and say, “When you asked the junior resident if he was leading the code, you unintentionally indicated that he was the most experienced, which made it more challenging for the female senior resident to lead the response.” In this way, the “invisible” implication of the nurse’s words—that the male resident was the most knowledgeable physician in the room—is made visible, and the female resident is relieved of responding.

Microaggressions do not occur in a vacuum; context matters. Before employing these strategies, consider when, where, and how you address microaggressions. These strategies validate and support those on the receiving end of microaggressions, and thus counteract their deleterious effects. The onus is on us: we must not be silent.

The authors have nothing to disclose.

“In the end, we will remember not the words of our enemies, but the silence of our friends.”

—Martin Luther King, Jr.

"Code Blue, Emergency Department Code Team to PACU.” A female senior resident dons her personal protective equipment and assembles her team. An enthusiastic male junior resident asks if he can accompany her, and off they go. They encounter a frantic scene in the post-anesthesia care unit (PACU). Before the senior resident can lead the rapid response, a PACU nurse addresses the junior resident: “You are leading the code, correct? What medications would you like?”

“Microaggressions” are subtle, commonplace exchanges that—whether intentional or unintentional—communicate disparaging messages to members of marginalized groups.¹ These groups often include women, members of racial/ethnic groups that are underrepresented in medicine, and lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals. Although an individual may not intend to cause harm, their words may still negatively impact the receiving party, who regularly experiences differential treatment based on sex, race, ethnicity, or other social identities. The effects of microaggressions extend beyond personal offense to include anxiety, depression, and even hypertension.^1,2

Addressing microaggressions can be challenging. Given that the recipients of microaggressions are often burdened with responding to them, it is important for bystanders to be empowered to respond as well. A bystander witnesses and recognizes the microaggression and can address it. Based on the work of Sue et al,³ we suggest that bystanders adopt the following strategies:

• Make the “invisible” visible. Many people do not perceive their actions as biased or prejudiced. It is therefore important to bring the implicit bias to the forefront by asking for clarification, naming the implication, or challenging the stereotype.
• Disarm the microaggression. Don’t be afraid to stop, deflect, disagree, or challenge what was said or done, thereby highlighting its potentially harmful impact. Another option is to interrupt the comment as it’s being said and redirect the conversation.
• Educate the speaker. Create a nonpunitive discussion by appealing to common values, promoting empathy, and increasing awareness of societal benefits. The speaker may become defensive and emphasize that their intent was not to cause harm. You must emphasize that, regardless of intent, the impact was hurtful. You may refocus the discussion with a simple statement such as, “I know you meant well, and…”
• Seek external support when needed. Addressing microaggressions can be emotionally taxing. Don’t be afraid to utilize community services, find a support group, or seek advice from professionals.

By virtue of being a neutral third party, bystanders who intervene may have greater success at explaining the impact of the microaggression. In doing so, the bystander also relieves the recipient of the microaggression of a burdensome response. In the above example, another provider in the PACU might pull the nurse aside later and say, “When you asked the junior resident if he was leading the code, you unintentionally indicated that he was the most experienced, which made it more challenging for the female senior resident to lead the response.” In this way, the “invisible” implication of the nurse’s words—that the male resident was the most knowledgeable physician in the room—is made visible, and the female resident is relieved of responding.

Microaggressions do not occur in a vacuum; context matters. Before employing these strategies, consider when, where, and how you address microaggressions. These strategies validate and support those on the receiving end of microaggressions, and thus counteract their deleterious effects. The onus is on us: we must not be silent.

The authors have nothing to disclose.

The negative symptoms of schizophrenia have been recognized for 100 years. Characterized by a loss of a function that should be present, negative symptoms include anhedonia, asociality, amotivation, and affective blunting. Individuals with schizophrenia who have a preponderance of negative symptoms (“deficit syndrome”) may comprise a special subset of patients. Compared with positive symptoms, negative symptoms are associated with worse global functioning and worse response to antipsychotic medication. Treatment of negative symptoms is challenging. Secondary negative symptoms—those that simulate or resemble primary negative symptoms but are attributable to another cause, such as major depressive disorder or the adverse effects of antipsychotic medication—need to be ruled out. Emerging evidence suggests that newer antipsychotics with novel mechanisms might be effective in treating negative symptoms. Antidepressants might also play a role.

This article describes types of negative symptoms, their clinical relevance, neuroanatomical and neurotransmission factors associated with negative symptoms, and current and future treatment options.

Modest improvements with antipsychotics

Schizophrenia affects an estimated 1% of the population.¹ Antipsychotic medication has been the mainstay of schizophrenia treatment since chlorpromazine was introduced in the 1950s; it was soon followed by many other antipsychotics. These first-generation antipsychotics (FGAs) were joined by second-generation antipsychotics (SGAs) in the 1990s. While SGAs are better tolerated and less likely to induce extrapyramidal side effects (EPS) than FGAs, they also are associated with troubling metabolic adverse effects (eg, impaired glucose tolerance).¹

All antipsychotics are believed to exert their therapeutic effects by blocking dopamine (D2) receptors and are effective in ameliorating the positive symptoms of schizophrenia, including hallucinations, delusions, bizarre behavior, disordered thinking, and agitation.¹ Early research had suggested that SGAs might also reduce the negative symptoms of schizophrenia, perhaps because they also block serotonin 2A receptors, a property thought to broaden their therapeutic profile. Over time, it became clear that neither FGAs nor SGAs conferred an advantage in treating negative symptoms, and that the observed improvements were modest.^2-5 However, recent research suggests that several newer antipsychotics might be effective in targeting negative symptoms.^2,6,7

History of negative symptoms

In the early 20th century, Swiss psychiatrist Eugen Bleuler coined the term schizophrenia to emphasize the cognitive impairment that occurs in patients with this illness, and which he conceptualized as a fragmenting of the psychic process.⁸ He believed that certain symptoms were fundamental to the illness, and described affective blunting, disturbance of association (ie, distorted thinking) autism (ie, impaired relationships), and ambivalence (ie, fragmented emotional responses). He viewed hallucinations and delusions as accessory symptoms because they were not unique to schizophrenia but were also found in other disorders (eg, mood disorders). Bleuler’s ideas took root, and generations of psychiatrists were taught his fundamental symptoms (“the 4 A’s”), the forerunner of today’s negative symptoms. Later, other experts chose to emphasize psychotic symptoms as most characteristic of schizophrenia, including Schneider’s “first-rank symptoms,” such as voices conversing or delusions of passivity.⁹

Negative symptoms were rediscovered in the 1970s and 1980s by psychiatric researchers interested in descriptive phenomenology.^10,11 Research confirmed the presence of a positive dimension in schizophrenia characterized by the loss of boundaries between the patient and the real world (eg, hallucinations, delusions), and a negative dimension characterized by the loss of a function that should be present, such as alogia and asociality. These experts carefully described negative symptoms and created scales to measure them, including the Scale for the Assessment of Negative Symptoms (SANS),¹² the Positive and Negative Syndrome Scale (PANSS),¹³ the Brief Negative Symptom Scale (BNSS),¹⁴ and the 16-item Negative Symptom Assessment (NSA-16).¹⁵ Contemporaneous to this work, a “deficit syndrome” was identified among patients with schizophrenia with prominent negative symptoms. The deficit syndrome is found in 25% to 30% of chronic cases.¹⁶ Negative symptoms are very common in patients with schizophrenia (Table 1⁹).^8,17

Early editions of the DSM defined schizophrenia mainly on the basis of disturbance of cognition, mood, and behavior, and a retreat from reality. With the publication of DSM-III in 1980, and in subsequent editions, schizophrenia was redefined as a relatively severe psychotic illness in which positive and negative symptoms were present, thereby acknowledging the importance of Bleuler’s fundamental symptoms. In DSM-5, negative symptoms are described as accounting for “a substantial portion of the morbidity associated with schizophrenia but are less prominent in other psychotic disorders.”¹⁸

Continue to: Types of negative symptoms

Types of negative symptoms

The following symptoms fall within the negative dimension¹⁹:

Alogia refers to the impoverished thinking and cognition that often occur in patients with schizophrenia. The patient’s thinking processes seem empty, turgid, or slow, as inferred from the patient’s speech. The 2 major manifestations of alogia are poverty of speech (nonfluent empty speech) and poverty of content of speech (fluent but empty speech). Examples of each appear in Table 2.¹⁹

Affective flattening or blunting manifests as a general impoverishment of emotional expression, reactivity, and feeling. Affective flattening can be assessed through observing a patient’s behavior and responsiveness during the interview.

Avolition-apathy manifests itself as a lack of energy and drive. Patients become inert and are unable to mobilize themselves to initiate or persist in completing many kinds of tasks.

Anhedonia-asociality encompasses the patient’s difficulties in experiencing interest or pleasure. It may express itself as a loss of interest in pleasurable activities, an inability to experience pleasure when participating in activities normally considered pleasurable, or a lack of involvement in social relationships.

Continue to: Attention

Attention is often poor in patients with severe mental illnesses. The patient may have trouble focusing his/her attention or may be able to focus only sporadically and erratically. He/she may ignore attempts to converse with him/her, wander away during an activity or a task, or appear to be inattentive when engaged in formal testing or interviewing.

Clinical relevance of negative symptoms

According to DSM-5, “Negative symptoms are more closely related to prognosis than are positive symptoms and tend to be the most persistent.”¹⁸ Research has shown that, compared with positive symptoms, negative symptoms are associated with greater impairment in overall functioning, social interaction, interpersonal relationships, economic functioning, and recreational activities.^1,3,5 Negative symptoms also are associated with poorer response to medication and a positive family history of schizophrenia. Research shows that negative symptoms are persistent over time, and, in fact, become more prominent as the patient ages, whereas positive symptoms become less prominent.²⁰

Secondary negative symptoms

Potential secondary causes of negative symptoms should be ruled out before concluding that the negative symptoms are due to schizophrenia.³ What might appear to be a negative symptom of schizophrenia, such as poor motivation or flattened affect, could be due to the presence of major depressive disorder. Such symptoms might resolve with treatment. Alternatively, a patient could have developed pseudoparkinsonism from antipsychotic medication and display unchanging facial expression and decreased spontaneous movements. These symptoms could resolve by adding benztropine or a similar medication to the treatment regimen. Other potential causes of secondary negative symptoms range from chronic substance abuse (eg, leading to poor grooming and hygiene), to paranoia and hallucinations, to sleep apnea inducing anergia and impersistence at work. Causes of secondary negative symptoms are outlined in Table 3.³

The neuroanatomy of negative symptoms

Although the neuroanatomical basis of negative symptoms has not been determined, neuroimaging studies have provided important clues.³ Structural brain imaging has consistently shown that negative symptoms in patients with schizophrenia correlate with decreased prefrontal white matter volume, anterior cingulate volume, insular cortex volume, left temporal cortex volume, and ventricular enlargement. Interestingly, volume loss starts before the appearance of negative symptoms.^21,22 Functional imaging has shown that negative symptoms correlate with reduced cerebral blood perfusion in frontal, prefrontal, posterior cingulate, thalamus, parietal, and striatal regions.^21,22 These findings may help explain the apathy, failure to initiate activities, and impaired social relatedness in patients with schizophrenia.

Neurotransmission and negative symptoms

Some experts have hypothesized that lowered cortical dopamine transmission in mesocortical pathways could give rise to negative symptoms, whereas excess transmission in subcortical structures leads to positive symptoms.²³ There is also evidence for a noradrenalin deficiency based on the finding that low levels of cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG), a noradrenaline metabolite, correlates with greater negative symptom severity.²⁴ The presence of a serotonin deficiency has been proposed based on evidence that negative symptoms might be mitigated by serotonergic agents.²⁵ More recently, some experts have posited that the dopamine D3 receptor might be involved in the etiology of negative symptoms. The dopamine D3 receptor activity is expressed in brain regions thought to control reward, emotions, and motivation.² Newer medications with novel mechanisms suggest that other neuro­transmitter pathways could be involved.^6,7

Continue to: Treatment options

 

 

Treatment options

Treating negative symptoms remains challenging and there are no clear answers. When they were introduced in the 1990s, SGAs were initially thought to be superior to FGAs in targeting negative symptoms. Subsequent research, including recent reviews and meta-analyses, has shown that SGAs are not superior to FGAs in treating negative symptoms, and the effect of either medication class on negative symptoms is modest.^2-5 One exception is amisulpride (not available in the United States), which is known to antagonize D2 and D3 receptors. A meta-analysis of the efficacy of antipsychotics in schizophrenia showed that amisulpride was significantly more effective than placebo in treating negative symptoms in 590 patients who received the medication.²⁶ The authors suggested that amisulpride was effective due to its binding to presynaptic receptors in the frontal cortex, thereby enhancing dopamine transmission in this region.

Cariprazine, which acts as a partial agonist at the D2 and D3 receptors, with a 10-fold affinity for the D3 receptor, also has shown promise in treating negative symptoms.² In a clinical trial of 460 patients with predominant negative symptoms, treatment with cariprazine led to a greater reduction in negative symptoms than risperidone, although the effect size was small.²⁷ In this study, cariprazine produced greater improvement in personal and social performance than risperidone. Animal data supports the possible use of cariprazine in treating negative symptoms.²⁸

Other promising agentsinclude roluperidone (MIN-101), in phase 3 of development, and SEP-363856, an investigational antipsychotic agent that is in phase 2 of development. Interestingly, roluperidone acts on serotonin 2A and sigma2 receptors and does not target dopamine receptors, whereas SEP-363856 is thought to activate trace amine-associated receptor 1 (TAAR1) in addition to serotonin 1A receptors.^6,7

Antidepressants also could be effective in reducing negative symptoms.³ A meta-analysis of randomized controlled trials evaluating the use of antidepressants as adjuncts to antipsychotic medications showed that adding an antidepressant was effective in reducing negative symptoms.²⁹ The mechanism by which an antidepressant might cause a reduction in negative symptoms is uncertain, and it is possible that the antidepressant might treat depressive symptoms that are causing or contributing to the negative symptoms.

Bottom Line

Negative symptoms in patients with schizophrenia are associated with a worse functional outcome and poorer response to antipsychotic medication than positive symptoms. First- and second-generation antipsychotics are largely ineffective in consistently treating negative symptoms. Antipsychotic medications that target the D3 receptor might be more effective. Roluperidone, which targets serotonin 2A and sigma receptors, and SEP-363856, which targets TAAR1 and serotonin 1A receptors, are being studied for their effects on negative symptoms.

Continue to: Related Resources

 

 

Related Resources

• Galderisi S, Färden A, Kaiser S. Dissecting negative symptoms of schizophrenia: History, assessment, pathophysiological mechanisms and treatment. Schizophr Res. 2017;186:1-2.
• Rabinowitz J. Treating negative symptoms of schizophrenia. Current Psychiatry. 2018;17(12):19-23.

Drug Brand Names

Benztropine • Cogentin
Cariprazine • Vraylar
Chlorpromazine • Promapar, Thorazine
Risperidone • Risperdal

The negative symptoms of schizophrenia have been recognized for 100 years. Characterized by a loss of a function that should be present, negative symptoms include anhedonia, asociality, amotivation, and affective blunting. Individuals with schizophrenia who have a preponderance of negative symptoms (“deficit syndrome”) may comprise a special subset of patients. Compared with positive symptoms, negative symptoms are associated with worse global functioning and worse response to antipsychotic medication. Treatment of negative symptoms is challenging. Secondary negative symptoms—those that simulate or resemble primary negative symptoms but are attributable to another cause, such as major depressive disorder or the adverse effects of antipsychotic medication—need to be ruled out. Emerging evidence suggests that newer antipsychotics with novel mechanisms might be effective in treating negative symptoms. Antidepressants might also play a role.

This article describes types of negative symptoms, their clinical relevance, neuroanatomical and neurotransmission factors associated with negative symptoms, and current and future treatment options.

Modest improvements with antipsychotics

Schizophrenia affects an estimated 1% of the population.¹ Antipsychotic medication has been the mainstay of schizophrenia treatment since chlorpromazine was introduced in the 1950s; it was soon followed by many other antipsychotics. These first-generation antipsychotics (FGAs) were joined by second-generation antipsychotics (SGAs) in the 1990s. While SGAs are better tolerated and less likely to induce extrapyramidal side effects (EPS) than FGAs, they also are associated with troubling metabolic adverse effects (eg, impaired glucose tolerance).¹

All antipsychotics are believed to exert their therapeutic effects by blocking dopamine (D2) receptors and are effective in ameliorating the positive symptoms of schizophrenia, including hallucinations, delusions, bizarre behavior, disordered thinking, and agitation.¹ Early research had suggested that SGAs might also reduce the negative symptoms of schizophrenia, perhaps because they also block serotonin 2A receptors, a property thought to broaden their therapeutic profile. Over time, it became clear that neither FGAs nor SGAs conferred an advantage in treating negative symptoms, and that the observed improvements were modest.^2-5 However, recent research suggests that several newer antipsychotics might be effective in targeting negative symptoms.^2,6,7

History of negative symptoms

In the early 20th century, Swiss psychiatrist Eugen Bleuler coined the term schizophrenia to emphasize the cognitive impairment that occurs in patients with this illness, and which he conceptualized as a fragmenting of the psychic process.⁸ He believed that certain symptoms were fundamental to the illness, and described affective blunting, disturbance of association (ie, distorted thinking) autism (ie, impaired relationships), and ambivalence (ie, fragmented emotional responses). He viewed hallucinations and delusions as accessory symptoms because they were not unique to schizophrenia but were also found in other disorders (eg, mood disorders). Bleuler’s ideas took root, and generations of psychiatrists were taught his fundamental symptoms (“the 4 A’s”), the forerunner of today’s negative symptoms. Later, other experts chose to emphasize psychotic symptoms as most characteristic of schizophrenia, including Schneider’s “first-rank symptoms,” such as voices conversing or delusions of passivity.⁹

Negative symptoms were rediscovered in the 1970s and 1980s by psychiatric researchers interested in descriptive phenomenology.^10,11 Research confirmed the presence of a positive dimension in schizophrenia characterized by the loss of boundaries between the patient and the real world (eg, hallucinations, delusions), and a negative dimension characterized by the loss of a function that should be present, such as alogia and asociality. These experts carefully described negative symptoms and created scales to measure them, including the Scale for the Assessment of Negative Symptoms (SANS),¹² the Positive and Negative Syndrome Scale (PANSS),¹³ the Brief Negative Symptom Scale (BNSS),¹⁴ and the 16-item Negative Symptom Assessment (NSA-16).¹⁵ Contemporaneous to this work, a “deficit syndrome” was identified among patients with schizophrenia with prominent negative symptoms. The deficit syndrome is found in 25% to 30% of chronic cases.¹⁶ Negative symptoms are very common in patients with schizophrenia (Table 1⁹).^8,17

Early editions of the DSM defined schizophrenia mainly on the basis of disturbance of cognition, mood, and behavior, and a retreat from reality. With the publication of DSM-III in 1980, and in subsequent editions, schizophrenia was redefined as a relatively severe psychotic illness in which positive and negative symptoms were present, thereby acknowledging the importance of Bleuler’s fundamental symptoms. In DSM-5, negative symptoms are described as accounting for “a substantial portion of the morbidity associated with schizophrenia but are less prominent in other psychotic disorders.”¹⁸

Continue to: Types of negative symptoms

Types of negative symptoms

The following symptoms fall within the negative dimension¹⁹:

Alogia refers to the impoverished thinking and cognition that often occur in patients with schizophrenia. The patient’s thinking processes seem empty, turgid, or slow, as inferred from the patient’s speech. The 2 major manifestations of alogia are poverty of speech (nonfluent empty speech) and poverty of content of speech (fluent but empty speech). Examples of each appear in Table 2.¹⁹

Affective flattening or blunting manifests as a general impoverishment of emotional expression, reactivity, and feeling. Affective flattening can be assessed through observing a patient’s behavior and responsiveness during the interview.

Avolition-apathy manifests itself as a lack of energy and drive. Patients become inert and are unable to mobilize themselves to initiate or persist in completing many kinds of tasks.

Anhedonia-asociality encompasses the patient’s difficulties in experiencing interest or pleasure. It may express itself as a loss of interest in pleasurable activities, an inability to experience pleasure when participating in activities normally considered pleasurable, or a lack of involvement in social relationships.

Continue to: Attention

Attention is often poor in patients with severe mental illnesses. The patient may have trouble focusing his/her attention or may be able to focus only sporadically and erratically. He/she may ignore attempts to converse with him/her, wander away during an activity or a task, or appear to be inattentive when engaged in formal testing or interviewing.

Clinical relevance of negative symptoms

According to DSM-5, “Negative symptoms are more closely related to prognosis than are positive symptoms and tend to be the most persistent.”¹⁸ Research has shown that, compared with positive symptoms, negative symptoms are associated with greater impairment in overall functioning, social interaction, interpersonal relationships, economic functioning, and recreational activities.^1,3,5 Negative symptoms also are associated with poorer response to medication and a positive family history of schizophrenia. Research shows that negative symptoms are persistent over time, and, in fact, become more prominent as the patient ages, whereas positive symptoms become less prominent.²⁰

Secondary negative symptoms

Potential secondary causes of negative symptoms should be ruled out before concluding that the negative symptoms are due to schizophrenia.³ What might appear to be a negative symptom of schizophrenia, such as poor motivation or flattened affect, could be due to the presence of major depressive disorder. Such symptoms might resolve with treatment. Alternatively, a patient could have developed pseudoparkinsonism from antipsychotic medication and display unchanging facial expression and decreased spontaneous movements. These symptoms could resolve by adding benztropine or a similar medication to the treatment regimen. Other potential causes of secondary negative symptoms range from chronic substance abuse (eg, leading to poor grooming and hygiene), to paranoia and hallucinations, to sleep apnea inducing anergia and impersistence at work. Causes of secondary negative symptoms are outlined in Table 3.³

The neuroanatomy of negative symptoms

Although the neuroanatomical basis of negative symptoms has not been determined, neuroimaging studies have provided important clues.³ Structural brain imaging has consistently shown that negative symptoms in patients with schizophrenia correlate with decreased prefrontal white matter volume, anterior cingulate volume, insular cortex volume, left temporal cortex volume, and ventricular enlargement. Interestingly, volume loss starts before the appearance of negative symptoms.^21,22 Functional imaging has shown that negative symptoms correlate with reduced cerebral blood perfusion in frontal, prefrontal, posterior cingulate, thalamus, parietal, and striatal regions.^21,22 These findings may help explain the apathy, failure to initiate activities, and impaired social relatedness in patients with schizophrenia.

Neurotransmission and negative symptoms

Some experts have hypothesized that lowered cortical dopamine transmission in mesocortical pathways could give rise to negative symptoms, whereas excess transmission in subcortical structures leads to positive symptoms.²³ There is also evidence for a noradrenalin deficiency based on the finding that low levels of cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG), a noradrenaline metabolite, correlates with greater negative symptom severity.²⁴ The presence of a serotonin deficiency has been proposed based on evidence that negative symptoms might be mitigated by serotonergic agents.²⁵ More recently, some experts have posited that the dopamine D3 receptor might be involved in the etiology of negative symptoms. The dopamine D3 receptor activity is expressed in brain regions thought to control reward, emotions, and motivation.² Newer medications with novel mechanisms suggest that other neuro­transmitter pathways could be involved.^6,7

Continue to: Treatment options

 

 

Treatment options

Treating negative symptoms remains challenging and there are no clear answers. When they were introduced in the 1990s, SGAs were initially thought to be superior to FGAs in targeting negative symptoms. Subsequent research, including recent reviews and meta-analyses, has shown that SGAs are not superior to FGAs in treating negative symptoms, and the effect of either medication class on negative symptoms is modest.^2-5 One exception is amisulpride (not available in the United States), which is known to antagonize D2 and D3 receptors. A meta-analysis of the efficacy of antipsychotics in schizophrenia showed that amisulpride was significantly more effective than placebo in treating negative symptoms in 590 patients who received the medication.²⁶ The authors suggested that amisulpride was effective due to its binding to presynaptic receptors in the frontal cortex, thereby enhancing dopamine transmission in this region.

Cariprazine, which acts as a partial agonist at the D2 and D3 receptors, with a 10-fold affinity for the D3 receptor, also has shown promise in treating negative symptoms.² In a clinical trial of 460 patients with predominant negative symptoms, treatment with cariprazine led to a greater reduction in negative symptoms than risperidone, although the effect size was small.²⁷ In this study, cariprazine produced greater improvement in personal and social performance than risperidone. Animal data supports the possible use of cariprazine in treating negative symptoms.²⁸

Other promising agentsinclude roluperidone (MIN-101), in phase 3 of development, and SEP-363856, an investigational antipsychotic agent that is in phase 2 of development. Interestingly, roluperidone acts on serotonin 2A and sigma2 receptors and does not target dopamine receptors, whereas SEP-363856 is thought to activate trace amine-associated receptor 1 (TAAR1) in addition to serotonin 1A receptors.^6,7

Antidepressants also could be effective in reducing negative symptoms.³ A meta-analysis of randomized controlled trials evaluating the use of antidepressants as adjuncts to antipsychotic medications showed that adding an antidepressant was effective in reducing negative symptoms.²⁹ The mechanism by which an antidepressant might cause a reduction in negative symptoms is uncertain, and it is possible that the antidepressant might treat depressive symptoms that are causing or contributing to the negative symptoms.

Bottom Line

Negative symptoms in patients with schizophrenia are associated with a worse functional outcome and poorer response to antipsychotic medication than positive symptoms. First- and second-generation antipsychotics are largely ineffective in consistently treating negative symptoms. Antipsychotic medications that target the D3 receptor might be more effective. Roluperidone, which targets serotonin 2A and sigma receptors, and SEP-363856, which targets TAAR1 and serotonin 1A receptors, are being studied for their effects on negative symptoms.

Continue to: Related Resources

 

 

Related Resources

• Galderisi S, Färden A, Kaiser S. Dissecting negative symptoms of schizophrenia: History, assessment, pathophysiological mechanisms and treatment. Schizophr Res. 2017;186:1-2.
• Rabinowitz J. Treating negative symptoms of schizophrenia. Current Psychiatry. 2018;17(12):19-23.

Drug Brand Names

Benztropine • Cogentin
Cariprazine • Vraylar
Chlorpromazine • Promapar, Thorazine
Risperidone • Risperdal

The negative symptoms of schizophrenia have been recognized for 100 years. Characterized by a loss of a function that should be present, negative symptoms include anhedonia, asociality, amotivation, and affective blunting. Individuals with schizophrenia who have a preponderance of negative symptoms (“deficit syndrome”) may comprise a special subset of patients. Compared with positive symptoms, negative symptoms are associated with worse global functioning and worse response to antipsychotic medication. Treatment of negative symptoms is challenging. Secondary negative symptoms—those that simulate or resemble primary negative symptoms but are attributable to another cause, such as major depressive disorder or the adverse effects of antipsychotic medication—need to be ruled out. Emerging evidence suggests that newer antipsychotics with novel mechanisms might be effective in treating negative symptoms. Antidepressants might also play a role.

This article describes types of negative symptoms, their clinical relevance, neuroanatomical and neurotransmission factors associated with negative symptoms, and current and future treatment options.

Modest improvements with antipsychotics

Schizophrenia affects an estimated 1% of the population.¹ Antipsychotic medication has been the mainstay of schizophrenia treatment since chlorpromazine was introduced in the 1950s; it was soon followed by many other antipsychotics. These first-generation antipsychotics (FGAs) were joined by second-generation antipsychotics (SGAs) in the 1990s. While SGAs are better tolerated and less likely to induce extrapyramidal side effects (EPS) than FGAs, they also are associated with troubling metabolic adverse effects (eg, impaired glucose tolerance).¹

All antipsychotics are believed to exert their therapeutic effects by blocking dopamine (D2) receptors and are effective in ameliorating the positive symptoms of schizophrenia, including hallucinations, delusions, bizarre behavior, disordered thinking, and agitation.¹ Early research had suggested that SGAs might also reduce the negative symptoms of schizophrenia, perhaps because they also block serotonin 2A receptors, a property thought to broaden their therapeutic profile. Over time, it became clear that neither FGAs nor SGAs conferred an advantage in treating negative symptoms, and that the observed improvements were modest.^2-5 However, recent research suggests that several newer antipsychotics might be effective in targeting negative symptoms.^2,6,7

History of negative symptoms

In the early 20th century, Swiss psychiatrist Eugen Bleuler coined the term schizophrenia to emphasize the cognitive impairment that occurs in patients with this illness, and which he conceptualized as a fragmenting of the psychic process.⁸ He believed that certain symptoms were fundamental to the illness, and described affective blunting, disturbance of association (ie, distorted thinking) autism (ie, impaired relationships), and ambivalence (ie, fragmented emotional responses). He viewed hallucinations and delusions as accessory symptoms because they were not unique to schizophrenia but were also found in other disorders (eg, mood disorders). Bleuler’s ideas took root, and generations of psychiatrists were taught his fundamental symptoms (“the 4 A’s”), the forerunner of today’s negative symptoms. Later, other experts chose to emphasize psychotic symptoms as most characteristic of schizophrenia, including Schneider’s “first-rank symptoms,” such as voices conversing or delusions of passivity.⁹

Negative symptoms were rediscovered in the 1970s and 1980s by psychiatric researchers interested in descriptive phenomenology.^10,11 Research confirmed the presence of a positive dimension in schizophrenia characterized by the loss of boundaries between the patient and the real world (eg, hallucinations, delusions), and a negative dimension characterized by the loss of a function that should be present, such as alogia and asociality. These experts carefully described negative symptoms and created scales to measure them, including the Scale for the Assessment of Negative Symptoms (SANS),¹² the Positive and Negative Syndrome Scale (PANSS),¹³ the Brief Negative Symptom Scale (BNSS),¹⁴ and the 16-item Negative Symptom Assessment (NSA-16).¹⁵ Contemporaneous to this work, a “deficit syndrome” was identified among patients with schizophrenia with prominent negative symptoms. The deficit syndrome is found in 25% to 30% of chronic cases.¹⁶ Negative symptoms are very common in patients with schizophrenia (Table 1⁹).^8,17

Early editions of the DSM defined schizophrenia mainly on the basis of disturbance of cognition, mood, and behavior, and a retreat from reality. With the publication of DSM-III in 1980, and in subsequent editions, schizophrenia was redefined as a relatively severe psychotic illness in which positive and negative symptoms were present, thereby acknowledging the importance of Bleuler’s fundamental symptoms. In DSM-5, negative symptoms are described as accounting for “a substantial portion of the morbidity associated with schizophrenia but are less prominent in other psychotic disorders.”¹⁸

Continue to: Types of negative symptoms

Types of negative symptoms

The following symptoms fall within the negative dimension¹⁹:

Alogia refers to the impoverished thinking and cognition that often occur in patients with schizophrenia. The patient’s thinking processes seem empty, turgid, or slow, as inferred from the patient’s speech. The 2 major manifestations of alogia are poverty of speech (nonfluent empty speech) and poverty of content of speech (fluent but empty speech). Examples of each appear in Table 2.¹⁹

Affective flattening or blunting manifests as a general impoverishment of emotional expression, reactivity, and feeling. Affective flattening can be assessed through observing a patient’s behavior and responsiveness during the interview.

Avolition-apathy manifests itself as a lack of energy and drive. Patients become inert and are unable to mobilize themselves to initiate or persist in completing many kinds of tasks.

Anhedonia-asociality encompasses the patient’s difficulties in experiencing interest or pleasure. It may express itself as a loss of interest in pleasurable activities, an inability to experience pleasure when participating in activities normally considered pleasurable, or a lack of involvement in social relationships.

Continue to: Attention

Attention is often poor in patients with severe mental illnesses. The patient may have trouble focusing his/her attention or may be able to focus only sporadically and erratically. He/she may ignore attempts to converse with him/her, wander away during an activity or a task, or appear to be inattentive when engaged in formal testing or interviewing.

Clinical relevance of negative symptoms

According to DSM-5, “Negative symptoms are more closely related to prognosis than are positive symptoms and tend to be the most persistent.”¹⁸ Research has shown that, compared with positive symptoms, negative symptoms are associated with greater impairment in overall functioning, social interaction, interpersonal relationships, economic functioning, and recreational activities.^1,3,5 Negative symptoms also are associated with poorer response to medication and a positive family history of schizophrenia. Research shows that negative symptoms are persistent over time, and, in fact, become more prominent as the patient ages, whereas positive symptoms become less prominent.²⁰

Secondary negative symptoms

Potential secondary causes of negative symptoms should be ruled out before concluding that the negative symptoms are due to schizophrenia.³ What might appear to be a negative symptom of schizophrenia, such as poor motivation or flattened affect, could be due to the presence of major depressive disorder. Such symptoms might resolve with treatment. Alternatively, a patient could have developed pseudoparkinsonism from antipsychotic medication and display unchanging facial expression and decreased spontaneous movements. These symptoms could resolve by adding benztropine or a similar medication to the treatment regimen. Other potential causes of secondary negative symptoms range from chronic substance abuse (eg, leading to poor grooming and hygiene), to paranoia and hallucinations, to sleep apnea inducing anergia and impersistence at work. Causes of secondary negative symptoms are outlined in Table 3.³

The neuroanatomy of negative symptoms

Although the neuroanatomical basis of negative symptoms has not been determined, neuroimaging studies have provided important clues.³ Structural brain imaging has consistently shown that negative symptoms in patients with schizophrenia correlate with decreased prefrontal white matter volume, anterior cingulate volume, insular cortex volume, left temporal cortex volume, and ventricular enlargement. Interestingly, volume loss starts before the appearance of negative symptoms.^21,22 Functional imaging has shown that negative symptoms correlate with reduced cerebral blood perfusion in frontal, prefrontal, posterior cingulate, thalamus, parietal, and striatal regions.^21,22 These findings may help explain the apathy, failure to initiate activities, and impaired social relatedness in patients with schizophrenia.

Neurotransmission and negative symptoms

Some experts have hypothesized that lowered cortical dopamine transmission in mesocortical pathways could give rise to negative symptoms, whereas excess transmission in subcortical structures leads to positive symptoms.²³ There is also evidence for a noradrenalin deficiency based on the finding that low levels of cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG), a noradrenaline metabolite, correlates with greater negative symptom severity.²⁴ The presence of a serotonin deficiency has been proposed based on evidence that negative symptoms might be mitigated by serotonergic agents.²⁵ More recently, some experts have posited that the dopamine D3 receptor might be involved in the etiology of negative symptoms. The dopamine D3 receptor activity is expressed in brain regions thought to control reward, emotions, and motivation.² Newer medications with novel mechanisms suggest that other neuro­transmitter pathways could be involved.^6,7

Continue to: Treatment options

 

 

Treatment options

Treating negative symptoms remains challenging and there are no clear answers. When they were introduced in the 1990s, SGAs were initially thought to be superior to FGAs in targeting negative symptoms. Subsequent research, including recent reviews and meta-analyses, has shown that SGAs are not superior to FGAs in treating negative symptoms, and the effect of either medication class on negative symptoms is modest.^2-5 One exception is amisulpride (not available in the United States), which is known to antagonize D2 and D3 receptors. A meta-analysis of the efficacy of antipsychotics in schizophrenia showed that amisulpride was significantly more effective than placebo in treating negative symptoms in 590 patients who received the medication.²⁶ The authors suggested that amisulpride was effective due to its binding to presynaptic receptors in the frontal cortex, thereby enhancing dopamine transmission in this region.

Cariprazine, which acts as a partial agonist at the D2 and D3 receptors, with a 10-fold affinity for the D3 receptor, also has shown promise in treating negative symptoms.² In a clinical trial of 460 patients with predominant negative symptoms, treatment with cariprazine led to a greater reduction in negative symptoms than risperidone, although the effect size was small.²⁷ In this study, cariprazine produced greater improvement in personal and social performance than risperidone. Animal data supports the possible use of cariprazine in treating negative symptoms.²⁸

Other promising agentsinclude roluperidone (MIN-101), in phase 3 of development, and SEP-363856, an investigational antipsychotic agent that is in phase 2 of development. Interestingly, roluperidone acts on serotonin 2A and sigma2 receptors and does not target dopamine receptors, whereas SEP-363856 is thought to activate trace amine-associated receptor 1 (TAAR1) in addition to serotonin 1A receptors.^6,7

Antidepressants also could be effective in reducing negative symptoms.³ A meta-analysis of randomized controlled trials evaluating the use of antidepressants as adjuncts to antipsychotic medications showed that adding an antidepressant was effective in reducing negative symptoms.²⁹ The mechanism by which an antidepressant might cause a reduction in negative symptoms is uncertain, and it is possible that the antidepressant might treat depressive symptoms that are causing or contributing to the negative symptoms.

Bottom Line

Negative symptoms in patients with schizophrenia are associated with a worse functional outcome and poorer response to antipsychotic medication than positive symptoms. First- and second-generation antipsychotics are largely ineffective in consistently treating negative symptoms. Antipsychotic medications that target the D3 receptor might be more effective. Roluperidone, which targets serotonin 2A and sigma receptors, and SEP-363856, which targets TAAR1 and serotonin 1A receptors, are being studied for their effects on negative symptoms.

Continue to: Related Resources

 

 

Related Resources

• Galderisi S, Färden A, Kaiser S. Dissecting negative symptoms of schizophrenia: History, assessment, pathophysiological mechanisms and treatment. Schizophr Res. 2017;186:1-2.
• Rabinowitz J. Treating negative symptoms of schizophrenia. Current Psychiatry. 2018;17(12):19-23.

Drug Brand Names

Benztropine • Cogentin
Cariprazine • Vraylar
Chlorpromazine • Promapar, Thorazine
Risperidone • Risperdal