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High rates of work-related trauma, PTSD in intern physicians
Work-related posttraumatic stress disorder is three times higher in interns than the general population, new research shows.
Investigators assessed PTSD in more than 1,100 physicians at the end of their internship year and found that a little over half reported work-related trauma exposure, and of these, 20% screened positive for PTSD.
Overall, 10% of participants screened positive for PTSD by the end of the internship year, compared with a 12-month PTSD prevalence of 3.6% in the general population.
“Work-related trauma exposure and PTSD are common and underdiscussed phenomena among intern physicians,” lead author Mary Vance, MD, assistant professor of psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview.
“I urge medical educators and policy makers to include this topic in their discussions about physician well-being and to implement effective interventions to mitigate the impact of work-related trauma and PTSD among physician trainees,” she said.
The study was published online June 8 in JAMA Network Open.
Burnout, depression, suicide
“Burnout, depression, and suicide are increasingly recognized as occupational mental health hazards among health care professionals, including physicians,” Dr. Vance said.
“However, in my professional experience as a physician and educator, despite observing anecdotal evidence among my peers and trainees that this is also an issue,” she added.
This gap prompted her “to investigate rates of work-related trauma exposure and PTSD among physicians.”
The researchers sent emails to 4,350 individuals during academic year 2018-2019, 2 months prior to starting internships. Of these, 2,129 agreed to participate and 1,134 (58.6% female, 61.6% non-Hispanic White; mean age, 27.52) completed the study.
Prior to beginning internship, participants completed a baseline survey that assessed demographic characteristics as well as medical education and psychological and psychosocial factors.
Participants completed follow-up surveys sent by email at 3, 6, 9, and 12 months of the internship year. The surveys assessed stressful life events, concern over perceived medical errors in the past 3 months, and number of hours worked over the past week.
At month 12, current PTSD and symptoms of depression and anxiety were also assessed using the Primary Care PTSD Screen for DSM-5, the 9-item Patient Health Questionnaire, and the Generalized Anxiety Disorder 7-item scale, respectively.
Participants were asked to self-report whether they ever had an episode of depression and to complete the Risky Families Questionnaire to assess if they had experienced childhood abuse, neglect, and family conflict. Additionally, they completed an 11-item scale developed specifically for the study regarding recent stressful events.
‘Crucible’ year
A total of 56.4% of respondents reported work-related trauma exposure, and among these, 19.0% screened positive for PTSD. One-tenth (10.8%) of the entire sample screened positive for PTSD by the end of internship year, which is three times higher than the 12-month prevalence of PTSD in the general population (3.6%), the authors noted.
Trauma exposure differed by specialty, ranging from 43.1% in anesthesiology to 72.4% in emergency medicine. Of the respondents in internal medicine, surgery, and medicine/pediatrics, 56.6%, 63.3%, and 71%, respectively, reported work-related trauma exposure.
Work-related PTSD also differed by specialty, ranging from 7.5% in ob.gyn. to 30.0% in pediatrics. Of respondents in internal medicine and family practice, 23.9% and 25.9%, respectively, reported work-related PTSD.
Dr. Vance called the intern year “a crucible, during which newly minted doctors receive intensive on-the-job training at the front lines of patient care [and] work long hours in rapidly shifting environments, often caring for critically ill patients.”
Work-related trauma exposure “is more likely to occur during this high-stress internship year than during the same year in the general population,” she said.
She noted that the “issue of workplace trauma and PTSD among health care workers became even more salient during the height of COVID,” adding that she expects it “to remain a pressure issue for healthcare workers in the post-COVID era.”
Call to action
Commenting on the study David A. Marcus, MD, chair, GME Physician Well-Being Committee, Northwell Health, New Hyde Park, N.Y., noted the study’s “relatively low response rate” is a “significant limitation” of the study.
An additional limitation is the lack of a baseline PTSD assessment, said Dr. Marcus, an assistant professor at Hofstra University, Hempstead, N.Y., who was not involved in the research.
Nevertheless, the “overall prevalence [of work-related PTSD] should serve as a call to action for physician leaders and for leaders in academic medicine,” he said.
Additionally, the study “reminds us that trauma-informed care should be an essential part of mental health support services provided to trainees and to physicians in general,” Dr. Marcus stated.
Also commenting on the study, Lotte N. Dyrbye, MD, professor of medicine and medical education, Mayo Clinic, Rochester, Minn., agreed.
“Organizational strategies should include system-level interventions to reduce the risk of frightening, horrible, or traumatic events from occurring in the workplace in the first place, as well as faculty development efforts to upskill teaching faculty in their ability to support trainees when such events do occur,” she said.
These approaches “should coincide with organizational efforts to support individual trainees by providing adequate time off after traumatic events, ensuring trainees can access affordable mental healthcare, and reducing other barriers to appropriate help-seeking, such as stigma, and efforts to build a culture of well-being,” suggested Dr. Dyrbye, who is codirector of the Mayo Clinic Program on Physician Wellbeing and was not involved in the study.
The study was supported by grants from the Blue Cross Blue Shield Foundation of Michigan and National Institutes of Health. Dr. Vance and coauthors, Dr. Marcus, and Dr. Dyrbye reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Work-related posttraumatic stress disorder is three times higher in interns than the general population, new research shows.
Investigators assessed PTSD in more than 1,100 physicians at the end of their internship year and found that a little over half reported work-related trauma exposure, and of these, 20% screened positive for PTSD.
Overall, 10% of participants screened positive for PTSD by the end of the internship year, compared with a 12-month PTSD prevalence of 3.6% in the general population.
“Work-related trauma exposure and PTSD are common and underdiscussed phenomena among intern physicians,” lead author Mary Vance, MD, assistant professor of psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview.
“I urge medical educators and policy makers to include this topic in their discussions about physician well-being and to implement effective interventions to mitigate the impact of work-related trauma and PTSD among physician trainees,” she said.
The study was published online June 8 in JAMA Network Open.
Burnout, depression, suicide
“Burnout, depression, and suicide are increasingly recognized as occupational mental health hazards among health care professionals, including physicians,” Dr. Vance said.
“However, in my professional experience as a physician and educator, despite observing anecdotal evidence among my peers and trainees that this is also an issue,” she added.
This gap prompted her “to investigate rates of work-related trauma exposure and PTSD among physicians.”
The researchers sent emails to 4,350 individuals during academic year 2018-2019, 2 months prior to starting internships. Of these, 2,129 agreed to participate and 1,134 (58.6% female, 61.6% non-Hispanic White; mean age, 27.52) completed the study.
Prior to beginning internship, participants completed a baseline survey that assessed demographic characteristics as well as medical education and psychological and psychosocial factors.
Participants completed follow-up surveys sent by email at 3, 6, 9, and 12 months of the internship year. The surveys assessed stressful life events, concern over perceived medical errors in the past 3 months, and number of hours worked over the past week.
At month 12, current PTSD and symptoms of depression and anxiety were also assessed using the Primary Care PTSD Screen for DSM-5, the 9-item Patient Health Questionnaire, and the Generalized Anxiety Disorder 7-item scale, respectively.
Participants were asked to self-report whether they ever had an episode of depression and to complete the Risky Families Questionnaire to assess if they had experienced childhood abuse, neglect, and family conflict. Additionally, they completed an 11-item scale developed specifically for the study regarding recent stressful events.
‘Crucible’ year
A total of 56.4% of respondents reported work-related trauma exposure, and among these, 19.0% screened positive for PTSD. One-tenth (10.8%) of the entire sample screened positive for PTSD by the end of internship year, which is three times higher than the 12-month prevalence of PTSD in the general population (3.6%), the authors noted.
Trauma exposure differed by specialty, ranging from 43.1% in anesthesiology to 72.4% in emergency medicine. Of the respondents in internal medicine, surgery, and medicine/pediatrics, 56.6%, 63.3%, and 71%, respectively, reported work-related trauma exposure.
Work-related PTSD also differed by specialty, ranging from 7.5% in ob.gyn. to 30.0% in pediatrics. Of respondents in internal medicine and family practice, 23.9% and 25.9%, respectively, reported work-related PTSD.
Dr. Vance called the intern year “a crucible, during which newly minted doctors receive intensive on-the-job training at the front lines of patient care [and] work long hours in rapidly shifting environments, often caring for critically ill patients.”
Work-related trauma exposure “is more likely to occur during this high-stress internship year than during the same year in the general population,” she said.
She noted that the “issue of workplace trauma and PTSD among health care workers became even more salient during the height of COVID,” adding that she expects it “to remain a pressure issue for healthcare workers in the post-COVID era.”
Call to action
Commenting on the study David A. Marcus, MD, chair, GME Physician Well-Being Committee, Northwell Health, New Hyde Park, N.Y., noted the study’s “relatively low response rate” is a “significant limitation” of the study.
An additional limitation is the lack of a baseline PTSD assessment, said Dr. Marcus, an assistant professor at Hofstra University, Hempstead, N.Y., who was not involved in the research.
Nevertheless, the “overall prevalence [of work-related PTSD] should serve as a call to action for physician leaders and for leaders in academic medicine,” he said.
Additionally, the study “reminds us that trauma-informed care should be an essential part of mental health support services provided to trainees and to physicians in general,” Dr. Marcus stated.
Also commenting on the study, Lotte N. Dyrbye, MD, professor of medicine and medical education, Mayo Clinic, Rochester, Minn., agreed.
“Organizational strategies should include system-level interventions to reduce the risk of frightening, horrible, or traumatic events from occurring in the workplace in the first place, as well as faculty development efforts to upskill teaching faculty in their ability to support trainees when such events do occur,” she said.
These approaches “should coincide with organizational efforts to support individual trainees by providing adequate time off after traumatic events, ensuring trainees can access affordable mental healthcare, and reducing other barriers to appropriate help-seeking, such as stigma, and efforts to build a culture of well-being,” suggested Dr. Dyrbye, who is codirector of the Mayo Clinic Program on Physician Wellbeing and was not involved in the study.
The study was supported by grants from the Blue Cross Blue Shield Foundation of Michigan and National Institutes of Health. Dr. Vance and coauthors, Dr. Marcus, and Dr. Dyrbye reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Work-related posttraumatic stress disorder is three times higher in interns than the general population, new research shows.
Investigators assessed PTSD in more than 1,100 physicians at the end of their internship year and found that a little over half reported work-related trauma exposure, and of these, 20% screened positive for PTSD.
Overall, 10% of participants screened positive for PTSD by the end of the internship year, compared with a 12-month PTSD prevalence of 3.6% in the general population.
“Work-related trauma exposure and PTSD are common and underdiscussed phenomena among intern physicians,” lead author Mary Vance, MD, assistant professor of psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview.
“I urge medical educators and policy makers to include this topic in their discussions about physician well-being and to implement effective interventions to mitigate the impact of work-related trauma and PTSD among physician trainees,” she said.
The study was published online June 8 in JAMA Network Open.
Burnout, depression, suicide
“Burnout, depression, and suicide are increasingly recognized as occupational mental health hazards among health care professionals, including physicians,” Dr. Vance said.
“However, in my professional experience as a physician and educator, despite observing anecdotal evidence among my peers and trainees that this is also an issue,” she added.
This gap prompted her “to investigate rates of work-related trauma exposure and PTSD among physicians.”
The researchers sent emails to 4,350 individuals during academic year 2018-2019, 2 months prior to starting internships. Of these, 2,129 agreed to participate and 1,134 (58.6% female, 61.6% non-Hispanic White; mean age, 27.52) completed the study.
Prior to beginning internship, participants completed a baseline survey that assessed demographic characteristics as well as medical education and psychological and psychosocial factors.
Participants completed follow-up surveys sent by email at 3, 6, 9, and 12 months of the internship year. The surveys assessed stressful life events, concern over perceived medical errors in the past 3 months, and number of hours worked over the past week.
At month 12, current PTSD and symptoms of depression and anxiety were also assessed using the Primary Care PTSD Screen for DSM-5, the 9-item Patient Health Questionnaire, and the Generalized Anxiety Disorder 7-item scale, respectively.
Participants were asked to self-report whether they ever had an episode of depression and to complete the Risky Families Questionnaire to assess if they had experienced childhood abuse, neglect, and family conflict. Additionally, they completed an 11-item scale developed specifically for the study regarding recent stressful events.
‘Crucible’ year
A total of 56.4% of respondents reported work-related trauma exposure, and among these, 19.0% screened positive for PTSD. One-tenth (10.8%) of the entire sample screened positive for PTSD by the end of internship year, which is three times higher than the 12-month prevalence of PTSD in the general population (3.6%), the authors noted.
Trauma exposure differed by specialty, ranging from 43.1% in anesthesiology to 72.4% in emergency medicine. Of the respondents in internal medicine, surgery, and medicine/pediatrics, 56.6%, 63.3%, and 71%, respectively, reported work-related trauma exposure.
Work-related PTSD also differed by specialty, ranging from 7.5% in ob.gyn. to 30.0% in pediatrics. Of respondents in internal medicine and family practice, 23.9% and 25.9%, respectively, reported work-related PTSD.
Dr. Vance called the intern year “a crucible, during which newly minted doctors receive intensive on-the-job training at the front lines of patient care [and] work long hours in rapidly shifting environments, often caring for critically ill patients.”
Work-related trauma exposure “is more likely to occur during this high-stress internship year than during the same year in the general population,” she said.
She noted that the “issue of workplace trauma and PTSD among health care workers became even more salient during the height of COVID,” adding that she expects it “to remain a pressure issue for healthcare workers in the post-COVID era.”
Call to action
Commenting on the study David A. Marcus, MD, chair, GME Physician Well-Being Committee, Northwell Health, New Hyde Park, N.Y., noted the study’s “relatively low response rate” is a “significant limitation” of the study.
An additional limitation is the lack of a baseline PTSD assessment, said Dr. Marcus, an assistant professor at Hofstra University, Hempstead, N.Y., who was not involved in the research.
Nevertheless, the “overall prevalence [of work-related PTSD] should serve as a call to action for physician leaders and for leaders in academic medicine,” he said.
Additionally, the study “reminds us that trauma-informed care should be an essential part of mental health support services provided to trainees and to physicians in general,” Dr. Marcus stated.
Also commenting on the study, Lotte N. Dyrbye, MD, professor of medicine and medical education, Mayo Clinic, Rochester, Minn., agreed.
“Organizational strategies should include system-level interventions to reduce the risk of frightening, horrible, or traumatic events from occurring in the workplace in the first place, as well as faculty development efforts to upskill teaching faculty in their ability to support trainees when such events do occur,” she said.
These approaches “should coincide with organizational efforts to support individual trainees by providing adequate time off after traumatic events, ensuring trainees can access affordable mental healthcare, and reducing other barriers to appropriate help-seeking, such as stigma, and efforts to build a culture of well-being,” suggested Dr. Dyrbye, who is codirector of the Mayo Clinic Program on Physician Wellbeing and was not involved in the study.
The study was supported by grants from the Blue Cross Blue Shield Foundation of Michigan and National Institutes of Health. Dr. Vance and coauthors, Dr. Marcus, and Dr. Dyrbye reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Ten killer steps to writing a great medical thriller
For many physicians and other professionals, aspirations of crafting a work of fiction are not uncommon — and with good reason. We are, after all, a generally well-disciplined bunch capable of completing complex tasks, and there is certainly no shortage of excitement and drama in medicine and surgery — ample fodder for thrilling stories. Nonetheless, writing a novel is a major commitment, and it requires persistence, patience, and dedicated time, especially for one with a busy medical career.
Getting started is not easy. Writing workshops are helpful, and in my case, I tried to mentor with some of the best. Before writing my novel, I attended workshops for aspiring novelists, given by noted physician authors Tess Gerritsen (Body Double, The Surgeon) and the late Michael Palmer (The Society, The Fifth Vial).
Writers are often advised to “write about what you know.” In my case, I combined my knowledge of medicine and my experience with the thoroughbred racing world to craft a thriller that one reviewer described as “Dick Francis meets Robin Cook.” For those who have never read the Dick Francis series, he was a renowned crime writer whose novels centered on horse racing in England. Having been an avid reader of both authors, that comparison was the ultimate compliment.
So against that backdrop, the novel Shedrow, along with some shared wisdom from a few legendary writers.
1. Start with the big “what if.” Any great story starts with that simple “what if” question. What if a series of high-profile executives in the managed care industry are serially murdered (Michael Palmer’s The Society)? What if a multimillion-dollar stallion dies suddenly under very mysterious circumstances on a supposedly secure farm in Kentucky (Dean DeLuke’s Shedrow)?
2. Put a MacGuffin to work in your story. Popularized by Alfred Hitchcock, the MacGuffin is that essential plot element that drives virtually all characters in the story, although it may be rather vague and meaningless to the story itself. In the iconic movie Pulp Fiction, the MacGuffin is the briefcase — everyone wants it, and we never do find out what’s in it.
3. Pacing is critical. Plot out the timeline of emotional highs and lows in a story. It should look like a rolling pattern of highs and lows that crescendo upward to the ultimate crisis. Take advantage of the fact that following any of those emotional peaks, you probably have the reader’s undivided attention. That would be a good time to provide backstory or fill in needed information for the reader – information that may be critical but perhaps not as exciting as what just transpired.
4. Torture your protagonists. Just when the reader thinks that the hero is finally home free, throw in another obstacle. Readers will empathize with the character and be drawn in by the unexpected hurdle.
5. Be original and surprise your readers. Create twists and turns that are totally unexpected, yet believable. This is easier said than done but will go a long way toward making your novel original, gripping, and unpredictable.
6. As a general rule, consider short sentences and short chapters. This is strictly a personal preference, but who can argue with James Patterson’s short chapters or with Robert Parker’s short and engaging sentences? Sentence length can be varied for effect, too, with shorter sentences serving to heighten action or increase tension.
7. Avoid the passive voice. Your readers want action. This is an important rule in almost any type of writing.
8. Keep descriptions brief. Long, drawn-out descriptions of the way characters look, or even setting descriptions, are easily overdone in a thriller. The thriller genre is very different from literary fiction in this regard. Stephen King advises writers to “just say what they see, then get on with the story.”
9. Sustain the reader’s interest throughout. Assess each chapter ending and determine whether the reader has been given enough reason to want to continue reading. Pose a question, end with a minor cliffhanger, or at least ensure that there is enough accumulated tension in the story.
10. Edit aggressively and cut out the fluff. Ernest Hemingway once confided to F. Scott Fitzgerald, “I write one page of masterpiece to 91 pages of shit. I try to put the shit in the wastebasket.”
Dr. DeLuke is professor emeritus of oral and facial surgery at Virginia Commonwealth University and author of the novel Shedrow.
A version of this article first appeared on Medscape.com.
For many physicians and other professionals, aspirations of crafting a work of fiction are not uncommon — and with good reason. We are, after all, a generally well-disciplined bunch capable of completing complex tasks, and there is certainly no shortage of excitement and drama in medicine and surgery — ample fodder for thrilling stories. Nonetheless, writing a novel is a major commitment, and it requires persistence, patience, and dedicated time, especially for one with a busy medical career.
Getting started is not easy. Writing workshops are helpful, and in my case, I tried to mentor with some of the best. Before writing my novel, I attended workshops for aspiring novelists, given by noted physician authors Tess Gerritsen (Body Double, The Surgeon) and the late Michael Palmer (The Society, The Fifth Vial).
Writers are often advised to “write about what you know.” In my case, I combined my knowledge of medicine and my experience with the thoroughbred racing world to craft a thriller that one reviewer described as “Dick Francis meets Robin Cook.” For those who have never read the Dick Francis series, he was a renowned crime writer whose novels centered on horse racing in England. Having been an avid reader of both authors, that comparison was the ultimate compliment.
So against that backdrop, the novel Shedrow, along with some shared wisdom from a few legendary writers.
1. Start with the big “what if.” Any great story starts with that simple “what if” question. What if a series of high-profile executives in the managed care industry are serially murdered (Michael Palmer’s The Society)? What if a multimillion-dollar stallion dies suddenly under very mysterious circumstances on a supposedly secure farm in Kentucky (Dean DeLuke’s Shedrow)?
2. Put a MacGuffin to work in your story. Popularized by Alfred Hitchcock, the MacGuffin is that essential plot element that drives virtually all characters in the story, although it may be rather vague and meaningless to the story itself. In the iconic movie Pulp Fiction, the MacGuffin is the briefcase — everyone wants it, and we never do find out what’s in it.
3. Pacing is critical. Plot out the timeline of emotional highs and lows in a story. It should look like a rolling pattern of highs and lows that crescendo upward to the ultimate crisis. Take advantage of the fact that following any of those emotional peaks, you probably have the reader’s undivided attention. That would be a good time to provide backstory or fill in needed information for the reader – information that may be critical but perhaps not as exciting as what just transpired.
4. Torture your protagonists. Just when the reader thinks that the hero is finally home free, throw in another obstacle. Readers will empathize with the character and be drawn in by the unexpected hurdle.
5. Be original and surprise your readers. Create twists and turns that are totally unexpected, yet believable. This is easier said than done but will go a long way toward making your novel original, gripping, and unpredictable.
6. As a general rule, consider short sentences and short chapters. This is strictly a personal preference, but who can argue with James Patterson’s short chapters or with Robert Parker’s short and engaging sentences? Sentence length can be varied for effect, too, with shorter sentences serving to heighten action or increase tension.
7. Avoid the passive voice. Your readers want action. This is an important rule in almost any type of writing.
8. Keep descriptions brief. Long, drawn-out descriptions of the way characters look, or even setting descriptions, are easily overdone in a thriller. The thriller genre is very different from literary fiction in this regard. Stephen King advises writers to “just say what they see, then get on with the story.”
9. Sustain the reader’s interest throughout. Assess each chapter ending and determine whether the reader has been given enough reason to want to continue reading. Pose a question, end with a minor cliffhanger, or at least ensure that there is enough accumulated tension in the story.
10. Edit aggressively and cut out the fluff. Ernest Hemingway once confided to F. Scott Fitzgerald, “I write one page of masterpiece to 91 pages of shit. I try to put the shit in the wastebasket.”
Dr. DeLuke is professor emeritus of oral and facial surgery at Virginia Commonwealth University and author of the novel Shedrow.
A version of this article first appeared on Medscape.com.
For many physicians and other professionals, aspirations of crafting a work of fiction are not uncommon — and with good reason. We are, after all, a generally well-disciplined bunch capable of completing complex tasks, and there is certainly no shortage of excitement and drama in medicine and surgery — ample fodder for thrilling stories. Nonetheless, writing a novel is a major commitment, and it requires persistence, patience, and dedicated time, especially for one with a busy medical career.
Getting started is not easy. Writing workshops are helpful, and in my case, I tried to mentor with some of the best. Before writing my novel, I attended workshops for aspiring novelists, given by noted physician authors Tess Gerritsen (Body Double, The Surgeon) and the late Michael Palmer (The Society, The Fifth Vial).
Writers are often advised to “write about what you know.” In my case, I combined my knowledge of medicine and my experience with the thoroughbred racing world to craft a thriller that one reviewer described as “Dick Francis meets Robin Cook.” For those who have never read the Dick Francis series, he was a renowned crime writer whose novels centered on horse racing in England. Having been an avid reader of both authors, that comparison was the ultimate compliment.
So against that backdrop, the novel Shedrow, along with some shared wisdom from a few legendary writers.
1. Start with the big “what if.” Any great story starts with that simple “what if” question. What if a series of high-profile executives in the managed care industry are serially murdered (Michael Palmer’s The Society)? What if a multimillion-dollar stallion dies suddenly under very mysterious circumstances on a supposedly secure farm in Kentucky (Dean DeLuke’s Shedrow)?
2. Put a MacGuffin to work in your story. Popularized by Alfred Hitchcock, the MacGuffin is that essential plot element that drives virtually all characters in the story, although it may be rather vague and meaningless to the story itself. In the iconic movie Pulp Fiction, the MacGuffin is the briefcase — everyone wants it, and we never do find out what’s in it.
3. Pacing is critical. Plot out the timeline of emotional highs and lows in a story. It should look like a rolling pattern of highs and lows that crescendo upward to the ultimate crisis. Take advantage of the fact that following any of those emotional peaks, you probably have the reader’s undivided attention. That would be a good time to provide backstory or fill in needed information for the reader – information that may be critical but perhaps not as exciting as what just transpired.
4. Torture your protagonists. Just when the reader thinks that the hero is finally home free, throw in another obstacle. Readers will empathize with the character and be drawn in by the unexpected hurdle.
5. Be original and surprise your readers. Create twists and turns that are totally unexpected, yet believable. This is easier said than done but will go a long way toward making your novel original, gripping, and unpredictable.
6. As a general rule, consider short sentences and short chapters. This is strictly a personal preference, but who can argue with James Patterson’s short chapters or with Robert Parker’s short and engaging sentences? Sentence length can be varied for effect, too, with shorter sentences serving to heighten action or increase tension.
7. Avoid the passive voice. Your readers want action. This is an important rule in almost any type of writing.
8. Keep descriptions brief. Long, drawn-out descriptions of the way characters look, or even setting descriptions, are easily overdone in a thriller. The thriller genre is very different from literary fiction in this regard. Stephen King advises writers to “just say what they see, then get on with the story.”
9. Sustain the reader’s interest throughout. Assess each chapter ending and determine whether the reader has been given enough reason to want to continue reading. Pose a question, end with a minor cliffhanger, or at least ensure that there is enough accumulated tension in the story.
10. Edit aggressively and cut out the fluff. Ernest Hemingway once confided to F. Scott Fitzgerald, “I write one page of masterpiece to 91 pages of shit. I try to put the shit in the wastebasket.”
Dr. DeLuke is professor emeritus of oral and facial surgery at Virginia Commonwealth University and author of the novel Shedrow.
A version of this article first appeared on Medscape.com.
Treating sleep apnea lowers MI and stroke risk
particularly for patients with moderate to severe OSA and those who are more adherent to CPAP therapy, a new study suggests.
“Most clinical trials on the effect of CPAP on CV diseases to date have focused on secondary CV prevention. This study contributes another piece of evidence about the role of CPAP therapy to prevent CV diseases,” said Diego R. Mazzotti, PhD, an assistant professor at the University of Kansas Medical Center, Kansas City.
“Our study, while observational, suggests that clinical trials focused on understanding how to sustain long-term CPAP adherence in obstructive sleep apnea patients are necessary and could be critical for optimizing comorbidity risk reduction,” Dr. Mazzotti said.
The study was presented at the virtual annual meeting of the Associated Professional Sleep Societies.
Good adherence important
The researchers analyzed the electronic health records of adults referred for a sleep study through the Kaiser Permanente Southern California health system. The sample included 11,145 adults without OSA, 13,898 with OSA who used CPAP, and 20,884 adults with OSA who did not use CPAP. None of them had CV disease at baseline. Median follow-up was 262 days.
The primary outcome was first occurrence of myocardial infarction, stroke, unstable angina, heart failure, or death caused by CV disease.
In adjusted models, adults with moderate to severe OSA (apnea-hypopnea index ≥15) who did not use CPAP were 71% more likely than those without OSA to have a first CV event (hazard ratio, 1.71; 95% CI, 1.11-2.64). However, the risk for a CV event during follow-up was 32% lower among OSA patients with any CPAP use (HR, 0.68; 95% CI, 0.50-0.93; P = .016).
The effect was mostly driven by those who used CPAP for at least 4 hours per night (HR, 0.60; 95% CI, 0.39-0.95). This association was stronger for those with moderate to severe OSA (HR, 0.56; 95% CI, 0.39-0.81).
“This study highlights the importance of long-term management of CPAP therapy in patients with moderate-severe OSA,” Dr. Mazzotti said in an interview.
“It suggests that maintaining good CPAP adherence might be beneficial for cardiovascular health, besides the already established benefits on quality of life, sleepiness, and other cardiometabolic functions,” he said.
Dr. Mazzotti said several mechanisms might explain the association between CPAP use and lower risk for CV events. “CPAP treats OSA by preventing respiratory pauses that occur during sleep, therefore preventing arousals, sleep fragmentation, and decreases in blood oxygen. These improved cardiorespiratory functions can be beneficial to avoid certain molecular changes that are known to contribute to cardiovascular risk, such as oxidative stress and inflammation,” he explained.
“However, specific studies fully understanding these mechanisms are necessary,” Dr. Mazzotti added.
In a comment, Nitun Verma, MD, a spokesperson for the American Academy of Sleep Medicine, said that “the frequent decreases in oxygen levels and fragmented sleep from apnea are associated with cardiovascular disorders. We know this from multiple studies. This, however, was a large study and strengthens the association between improving apnea and reduced serious cardiovascular events.”
Funding for the study was provided by the American Academy of Sleep Medicine Foundation and the American Heart Association. Dr. Mazzotti and Dr. Verma disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
particularly for patients with moderate to severe OSA and those who are more adherent to CPAP therapy, a new study suggests.
“Most clinical trials on the effect of CPAP on CV diseases to date have focused on secondary CV prevention. This study contributes another piece of evidence about the role of CPAP therapy to prevent CV diseases,” said Diego R. Mazzotti, PhD, an assistant professor at the University of Kansas Medical Center, Kansas City.
“Our study, while observational, suggests that clinical trials focused on understanding how to sustain long-term CPAP adherence in obstructive sleep apnea patients are necessary and could be critical for optimizing comorbidity risk reduction,” Dr. Mazzotti said.
The study was presented at the virtual annual meeting of the Associated Professional Sleep Societies.
Good adherence important
The researchers analyzed the electronic health records of adults referred for a sleep study through the Kaiser Permanente Southern California health system. The sample included 11,145 adults without OSA, 13,898 with OSA who used CPAP, and 20,884 adults with OSA who did not use CPAP. None of them had CV disease at baseline. Median follow-up was 262 days.
The primary outcome was first occurrence of myocardial infarction, stroke, unstable angina, heart failure, or death caused by CV disease.
In adjusted models, adults with moderate to severe OSA (apnea-hypopnea index ≥15) who did not use CPAP were 71% more likely than those without OSA to have a first CV event (hazard ratio, 1.71; 95% CI, 1.11-2.64). However, the risk for a CV event during follow-up was 32% lower among OSA patients with any CPAP use (HR, 0.68; 95% CI, 0.50-0.93; P = .016).
The effect was mostly driven by those who used CPAP for at least 4 hours per night (HR, 0.60; 95% CI, 0.39-0.95). This association was stronger for those with moderate to severe OSA (HR, 0.56; 95% CI, 0.39-0.81).
“This study highlights the importance of long-term management of CPAP therapy in patients with moderate-severe OSA,” Dr. Mazzotti said in an interview.
“It suggests that maintaining good CPAP adherence might be beneficial for cardiovascular health, besides the already established benefits on quality of life, sleepiness, and other cardiometabolic functions,” he said.
Dr. Mazzotti said several mechanisms might explain the association between CPAP use and lower risk for CV events. “CPAP treats OSA by preventing respiratory pauses that occur during sleep, therefore preventing arousals, sleep fragmentation, and decreases in blood oxygen. These improved cardiorespiratory functions can be beneficial to avoid certain molecular changes that are known to contribute to cardiovascular risk, such as oxidative stress and inflammation,” he explained.
“However, specific studies fully understanding these mechanisms are necessary,” Dr. Mazzotti added.
In a comment, Nitun Verma, MD, a spokesperson for the American Academy of Sleep Medicine, said that “the frequent decreases in oxygen levels and fragmented sleep from apnea are associated with cardiovascular disorders. We know this from multiple studies. This, however, was a large study and strengthens the association between improving apnea and reduced serious cardiovascular events.”
Funding for the study was provided by the American Academy of Sleep Medicine Foundation and the American Heart Association. Dr. Mazzotti and Dr. Verma disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
particularly for patients with moderate to severe OSA and those who are more adherent to CPAP therapy, a new study suggests.
“Most clinical trials on the effect of CPAP on CV diseases to date have focused on secondary CV prevention. This study contributes another piece of evidence about the role of CPAP therapy to prevent CV diseases,” said Diego R. Mazzotti, PhD, an assistant professor at the University of Kansas Medical Center, Kansas City.
“Our study, while observational, suggests that clinical trials focused on understanding how to sustain long-term CPAP adherence in obstructive sleep apnea patients are necessary and could be critical for optimizing comorbidity risk reduction,” Dr. Mazzotti said.
The study was presented at the virtual annual meeting of the Associated Professional Sleep Societies.
Good adherence important
The researchers analyzed the electronic health records of adults referred for a sleep study through the Kaiser Permanente Southern California health system. The sample included 11,145 adults without OSA, 13,898 with OSA who used CPAP, and 20,884 adults with OSA who did not use CPAP. None of them had CV disease at baseline. Median follow-up was 262 days.
The primary outcome was first occurrence of myocardial infarction, stroke, unstable angina, heart failure, or death caused by CV disease.
In adjusted models, adults with moderate to severe OSA (apnea-hypopnea index ≥15) who did not use CPAP were 71% more likely than those without OSA to have a first CV event (hazard ratio, 1.71; 95% CI, 1.11-2.64). However, the risk for a CV event during follow-up was 32% lower among OSA patients with any CPAP use (HR, 0.68; 95% CI, 0.50-0.93; P = .016).
The effect was mostly driven by those who used CPAP for at least 4 hours per night (HR, 0.60; 95% CI, 0.39-0.95). This association was stronger for those with moderate to severe OSA (HR, 0.56; 95% CI, 0.39-0.81).
“This study highlights the importance of long-term management of CPAP therapy in patients with moderate-severe OSA,” Dr. Mazzotti said in an interview.
“It suggests that maintaining good CPAP adherence might be beneficial for cardiovascular health, besides the already established benefits on quality of life, sleepiness, and other cardiometabolic functions,” he said.
Dr. Mazzotti said several mechanisms might explain the association between CPAP use and lower risk for CV events. “CPAP treats OSA by preventing respiratory pauses that occur during sleep, therefore preventing arousals, sleep fragmentation, and decreases in blood oxygen. These improved cardiorespiratory functions can be beneficial to avoid certain molecular changes that are known to contribute to cardiovascular risk, such as oxidative stress and inflammation,” he explained.
“However, specific studies fully understanding these mechanisms are necessary,” Dr. Mazzotti added.
In a comment, Nitun Verma, MD, a spokesperson for the American Academy of Sleep Medicine, said that “the frequent decreases in oxygen levels and fragmented sleep from apnea are associated with cardiovascular disorders. We know this from multiple studies. This, however, was a large study and strengthens the association between improving apnea and reduced serious cardiovascular events.”
Funding for the study was provided by the American Academy of Sleep Medicine Foundation and the American Heart Association. Dr. Mazzotti and Dr. Verma disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SLEEP 2021
Memory benefit seen with antihypertensives crossing blood-brain barrier
Over a 3-year period, cognitively normal older adults taking BBB-crossing antihypertensives demonstrated superior verbal memory, compared with similar individuals receiving non–BBB-crossing antihypertensives, reported lead author Jean K. Ho, PhD, of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, and colleagues.
According to the investigators, the findings add color to a known link between hypertension and neurologic degeneration, and may aid the search for new therapeutic targets.
“Hypertension is a well-established risk factor for cognitive decline and dementia, possibly through its effects on both cerebrovascular disease and Alzheimer’s disease,” Dr. Ho and colleagues wrote in Hypertension. “Studies of antihypertensive treatments have reported possible salutary effects on cognition and cerebrovascular disease, as well as Alzheimer’s disease neuropathology.”
In a previous study, individuals younger than 75 years exposed to antihypertensives had an 8% decreased risk of dementia per year of use, while another trial showed that intensive blood pressure–lowering therapy reduced mild cognitive impairment by 19%.
“Despite these encouraging findings ... larger meta-analytic studies have been hampered by the fact that pharmacokinetic properties are typically not considered in existing studies or routine clinical practice,” wrote Dr. Ho and colleagues. “The present study sought to fill this gap [in that it was] a large and longitudinal meta-analytic study of existing data recoded to assess the effects of BBB-crossing potential in renin-angiotensin system [RAS] treatments among hypertensive adults.”
Methods and results
The meta-analysis included randomized clinical trials, prospective cohort studies, and retrospective observational studies. The researchers assessed data on 12,849 individuals from 14 cohorts that received either BBB-crossing or non–BBB-crossing antihypertensives.
The BBB-crossing properties of RAS treatments were identified by a literature review. Of ACE inhibitors, captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as BBB crossing, and benazepril, enalapril, moexipril, and quinapril were classified as non–BBB-crossing. Of ARBs, telmisartan and candesartan were considered BBB-crossing, and olmesartan, eprosartan, irbesartan, and losartan were tagged as non–BBB-crossing.
Cognition was assessed via the following seven domains: executive function, attention, verbal memory learning, language, mental status, recall, and processing speed.
Compared with individuals taking non–BBB-crossing antihypertensives, those taking BBB-crossing agents had significantly superior verbal memory (recall), with a maximum effect size of 0.07 (P = .03).
According to the investigators, this finding was particularly noteworthy, as the BBB-crossing group had relatively higher vascular risk burden and lower mean education level.
“These differences make it all the more remarkable that the BBB-crossing group displayed better memory ability over time despite these cognitive disadvantages,” the investigators wrote.
Still, not all the findings favored BBB-crossing agents. Individuals in the BBB-crossing group had relatively inferior attention ability, with a minimum effect size of –0.17 (P = .02).
The other cognitive measures were not significantly different between groups.
Clinicians may consider findings after accounting for other factors
Principal investigator Daniel A. Nation, PhD, associate professor of psychological science and a faculty member of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, suggested that the small difference in verbal memory between groups could be clinically significant over a longer period of time.
“Although the overall effect size was pretty small, if you look at how long it would take for someone [with dementia] to progress over many years of decline, it would actually end up being a pretty big effect,” Dr. Nation said in an interview. “Small effect sizes could actually end up preventing a lot of cases of dementia,” he added.
The conflicting results in the BBB-crossing group – better verbal memory but worse attention ability – were “surprising,” he noted.
“I sort of didn’t believe it at first,” Dr. Nation said, “because the memory finding is sort of replication – we’d observed the same exact effect on memory in a smaller sample in another study. ... The attention [finding], going another way, was a new thing.”
Dr. Nation suggested that the intergroup differences in attention ability may stem from idiosyncrasies of the tests used to measure that domain, which can be impacted by cardiovascular or brain vascular disease. Or it could be caused by something else entirely, he said, noting that further investigation is needed.
He added that the improvements in verbal memory within the BBB-crossing group could be caused by direct effects on the brain. He pointed out that certain ACE polymorphisms have been linked with Alzheimer’s disease risk, and those same polymorphisms, in animal models, lead to neurodegeneration, with reversal possible through administration of ACE inhibitors.
“It could be that what we’re observing has nothing really to do with blood pressure,” Dr. Nation explained. “This could be a neuronal effect on learning memory systems.”
He went on to suggest that clinicians may consider these findings when selecting antihypertensive agents for their patients, with the caveat that all other prescribing factors have already been taking to account.
“In the event that you’re going to give an ACE inhibitor or an angiotensin receptor blocker anyway, and it ends up being a somewhat arbitrary decision in terms of which specific drug you’re going to give, then perhaps this is a piece of information you would take into account – that one gets in the brain and one doesn’t – in somebody at risk for cognitive decline,” Dr. Nation said.
Exact mechanisms of action unknown
Hélène Girouard, PhD, assistant professor of pharmacology and physiology at the University of Montreal, said in an interview that the findings are “of considerable importance, knowing that brain alterations could begin as much as 30 years before manifestation of dementia.”
Since 2003, Dr. Girouard has been studying the cognitive effects of antihypertensive medications. She noted that previous studies involving rodents “have shown beneficial effects [of BBB-crossing antihypertensive drugs] on cognition independent of their effects on blood pressure.”
The drugs’ exact mechanisms of action, however, remain elusive, according to Dr. Girouard, who offered several possible explanations, including amelioration of BBB disruption, brain inflammation, cerebral blood flow dysregulation, cholinergic dysfunction, and neurologic deficits. “Whether these mechanisms may explain Ho and colleagues’ observations remains to be established,” she added.
Andrea L. Schneider, MD, PhD, assistant professor of neurology at the University of Pennsylvania, Philadelphia, applauded the study, but ultimately suggested that more research is needed to impact clinical decision-making.
“The results of this important and well-done study suggest that further investigation into targeted mechanism-based approaches to selecting hypertension treatment agents, with a specific focus on cognitive outcomes, is warranted,” Dr. Schneider said in an interview. “Before changing clinical practice, further work is necessary to disentangle contributions of medication mechanism, comorbid vascular risk factors, and achieved blood pressure reduction, among others.”
The investigators disclosed support from the National Institutes of Health, the Alzheimer’s Association, the Waksman Foundation of Japan, and others. The interviewees reported no relevant conflicts of interest.
Over a 3-year period, cognitively normal older adults taking BBB-crossing antihypertensives demonstrated superior verbal memory, compared with similar individuals receiving non–BBB-crossing antihypertensives, reported lead author Jean K. Ho, PhD, of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, and colleagues.
According to the investigators, the findings add color to a known link between hypertension and neurologic degeneration, and may aid the search for new therapeutic targets.
“Hypertension is a well-established risk factor for cognitive decline and dementia, possibly through its effects on both cerebrovascular disease and Alzheimer’s disease,” Dr. Ho and colleagues wrote in Hypertension. “Studies of antihypertensive treatments have reported possible salutary effects on cognition and cerebrovascular disease, as well as Alzheimer’s disease neuropathology.”
In a previous study, individuals younger than 75 years exposed to antihypertensives had an 8% decreased risk of dementia per year of use, while another trial showed that intensive blood pressure–lowering therapy reduced mild cognitive impairment by 19%.
“Despite these encouraging findings ... larger meta-analytic studies have been hampered by the fact that pharmacokinetic properties are typically not considered in existing studies or routine clinical practice,” wrote Dr. Ho and colleagues. “The present study sought to fill this gap [in that it was] a large and longitudinal meta-analytic study of existing data recoded to assess the effects of BBB-crossing potential in renin-angiotensin system [RAS] treatments among hypertensive adults.”
Methods and results
The meta-analysis included randomized clinical trials, prospective cohort studies, and retrospective observational studies. The researchers assessed data on 12,849 individuals from 14 cohorts that received either BBB-crossing or non–BBB-crossing antihypertensives.
The BBB-crossing properties of RAS treatments were identified by a literature review. Of ACE inhibitors, captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as BBB crossing, and benazepril, enalapril, moexipril, and quinapril were classified as non–BBB-crossing. Of ARBs, telmisartan and candesartan were considered BBB-crossing, and olmesartan, eprosartan, irbesartan, and losartan were tagged as non–BBB-crossing.
Cognition was assessed via the following seven domains: executive function, attention, verbal memory learning, language, mental status, recall, and processing speed.
Compared with individuals taking non–BBB-crossing antihypertensives, those taking BBB-crossing agents had significantly superior verbal memory (recall), with a maximum effect size of 0.07 (P = .03).
According to the investigators, this finding was particularly noteworthy, as the BBB-crossing group had relatively higher vascular risk burden and lower mean education level.
“These differences make it all the more remarkable that the BBB-crossing group displayed better memory ability over time despite these cognitive disadvantages,” the investigators wrote.
Still, not all the findings favored BBB-crossing agents. Individuals in the BBB-crossing group had relatively inferior attention ability, with a minimum effect size of –0.17 (P = .02).
The other cognitive measures were not significantly different between groups.
Clinicians may consider findings after accounting for other factors
Principal investigator Daniel A. Nation, PhD, associate professor of psychological science and a faculty member of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, suggested that the small difference in verbal memory between groups could be clinically significant over a longer period of time.
“Although the overall effect size was pretty small, if you look at how long it would take for someone [with dementia] to progress over many years of decline, it would actually end up being a pretty big effect,” Dr. Nation said in an interview. “Small effect sizes could actually end up preventing a lot of cases of dementia,” he added.
The conflicting results in the BBB-crossing group – better verbal memory but worse attention ability – were “surprising,” he noted.
“I sort of didn’t believe it at first,” Dr. Nation said, “because the memory finding is sort of replication – we’d observed the same exact effect on memory in a smaller sample in another study. ... The attention [finding], going another way, was a new thing.”
Dr. Nation suggested that the intergroup differences in attention ability may stem from idiosyncrasies of the tests used to measure that domain, which can be impacted by cardiovascular or brain vascular disease. Or it could be caused by something else entirely, he said, noting that further investigation is needed.
He added that the improvements in verbal memory within the BBB-crossing group could be caused by direct effects on the brain. He pointed out that certain ACE polymorphisms have been linked with Alzheimer’s disease risk, and those same polymorphisms, in animal models, lead to neurodegeneration, with reversal possible through administration of ACE inhibitors.
“It could be that what we’re observing has nothing really to do with blood pressure,” Dr. Nation explained. “This could be a neuronal effect on learning memory systems.”
He went on to suggest that clinicians may consider these findings when selecting antihypertensive agents for their patients, with the caveat that all other prescribing factors have already been taking to account.
“In the event that you’re going to give an ACE inhibitor or an angiotensin receptor blocker anyway, and it ends up being a somewhat arbitrary decision in terms of which specific drug you’re going to give, then perhaps this is a piece of information you would take into account – that one gets in the brain and one doesn’t – in somebody at risk for cognitive decline,” Dr. Nation said.
Exact mechanisms of action unknown
Hélène Girouard, PhD, assistant professor of pharmacology and physiology at the University of Montreal, said in an interview that the findings are “of considerable importance, knowing that brain alterations could begin as much as 30 years before manifestation of dementia.”
Since 2003, Dr. Girouard has been studying the cognitive effects of antihypertensive medications. She noted that previous studies involving rodents “have shown beneficial effects [of BBB-crossing antihypertensive drugs] on cognition independent of their effects on blood pressure.”
The drugs’ exact mechanisms of action, however, remain elusive, according to Dr. Girouard, who offered several possible explanations, including amelioration of BBB disruption, brain inflammation, cerebral blood flow dysregulation, cholinergic dysfunction, and neurologic deficits. “Whether these mechanisms may explain Ho and colleagues’ observations remains to be established,” she added.
Andrea L. Schneider, MD, PhD, assistant professor of neurology at the University of Pennsylvania, Philadelphia, applauded the study, but ultimately suggested that more research is needed to impact clinical decision-making.
“The results of this important and well-done study suggest that further investigation into targeted mechanism-based approaches to selecting hypertension treatment agents, with a specific focus on cognitive outcomes, is warranted,” Dr. Schneider said in an interview. “Before changing clinical practice, further work is necessary to disentangle contributions of medication mechanism, comorbid vascular risk factors, and achieved blood pressure reduction, among others.”
The investigators disclosed support from the National Institutes of Health, the Alzheimer’s Association, the Waksman Foundation of Japan, and others. The interviewees reported no relevant conflicts of interest.
Over a 3-year period, cognitively normal older adults taking BBB-crossing antihypertensives demonstrated superior verbal memory, compared with similar individuals receiving non–BBB-crossing antihypertensives, reported lead author Jean K. Ho, PhD, of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, and colleagues.
According to the investigators, the findings add color to a known link between hypertension and neurologic degeneration, and may aid the search for new therapeutic targets.
“Hypertension is a well-established risk factor for cognitive decline and dementia, possibly through its effects on both cerebrovascular disease and Alzheimer’s disease,” Dr. Ho and colleagues wrote in Hypertension. “Studies of antihypertensive treatments have reported possible salutary effects on cognition and cerebrovascular disease, as well as Alzheimer’s disease neuropathology.”
In a previous study, individuals younger than 75 years exposed to antihypertensives had an 8% decreased risk of dementia per year of use, while another trial showed that intensive blood pressure–lowering therapy reduced mild cognitive impairment by 19%.
“Despite these encouraging findings ... larger meta-analytic studies have been hampered by the fact that pharmacokinetic properties are typically not considered in existing studies or routine clinical practice,” wrote Dr. Ho and colleagues. “The present study sought to fill this gap [in that it was] a large and longitudinal meta-analytic study of existing data recoded to assess the effects of BBB-crossing potential in renin-angiotensin system [RAS] treatments among hypertensive adults.”
Methods and results
The meta-analysis included randomized clinical trials, prospective cohort studies, and retrospective observational studies. The researchers assessed data on 12,849 individuals from 14 cohorts that received either BBB-crossing or non–BBB-crossing antihypertensives.
The BBB-crossing properties of RAS treatments were identified by a literature review. Of ACE inhibitors, captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as BBB crossing, and benazepril, enalapril, moexipril, and quinapril were classified as non–BBB-crossing. Of ARBs, telmisartan and candesartan were considered BBB-crossing, and olmesartan, eprosartan, irbesartan, and losartan were tagged as non–BBB-crossing.
Cognition was assessed via the following seven domains: executive function, attention, verbal memory learning, language, mental status, recall, and processing speed.
Compared with individuals taking non–BBB-crossing antihypertensives, those taking BBB-crossing agents had significantly superior verbal memory (recall), with a maximum effect size of 0.07 (P = .03).
According to the investigators, this finding was particularly noteworthy, as the BBB-crossing group had relatively higher vascular risk burden and lower mean education level.
“These differences make it all the more remarkable that the BBB-crossing group displayed better memory ability over time despite these cognitive disadvantages,” the investigators wrote.
Still, not all the findings favored BBB-crossing agents. Individuals in the BBB-crossing group had relatively inferior attention ability, with a minimum effect size of –0.17 (P = .02).
The other cognitive measures were not significantly different between groups.
Clinicians may consider findings after accounting for other factors
Principal investigator Daniel A. Nation, PhD, associate professor of psychological science and a faculty member of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, suggested that the small difference in verbal memory between groups could be clinically significant over a longer period of time.
“Although the overall effect size was pretty small, if you look at how long it would take for someone [with dementia] to progress over many years of decline, it would actually end up being a pretty big effect,” Dr. Nation said in an interview. “Small effect sizes could actually end up preventing a lot of cases of dementia,” he added.
The conflicting results in the BBB-crossing group – better verbal memory but worse attention ability – were “surprising,” he noted.
“I sort of didn’t believe it at first,” Dr. Nation said, “because the memory finding is sort of replication – we’d observed the same exact effect on memory in a smaller sample in another study. ... The attention [finding], going another way, was a new thing.”
Dr. Nation suggested that the intergroup differences in attention ability may stem from idiosyncrasies of the tests used to measure that domain, which can be impacted by cardiovascular or brain vascular disease. Or it could be caused by something else entirely, he said, noting that further investigation is needed.
He added that the improvements in verbal memory within the BBB-crossing group could be caused by direct effects on the brain. He pointed out that certain ACE polymorphisms have been linked with Alzheimer’s disease risk, and those same polymorphisms, in animal models, lead to neurodegeneration, with reversal possible through administration of ACE inhibitors.
“It could be that what we’re observing has nothing really to do with blood pressure,” Dr. Nation explained. “This could be a neuronal effect on learning memory systems.”
He went on to suggest that clinicians may consider these findings when selecting antihypertensive agents for their patients, with the caveat that all other prescribing factors have already been taking to account.
“In the event that you’re going to give an ACE inhibitor or an angiotensin receptor blocker anyway, and it ends up being a somewhat arbitrary decision in terms of which specific drug you’re going to give, then perhaps this is a piece of information you would take into account – that one gets in the brain and one doesn’t – in somebody at risk for cognitive decline,” Dr. Nation said.
Exact mechanisms of action unknown
Hélène Girouard, PhD, assistant professor of pharmacology and physiology at the University of Montreal, said in an interview that the findings are “of considerable importance, knowing that brain alterations could begin as much as 30 years before manifestation of dementia.”
Since 2003, Dr. Girouard has been studying the cognitive effects of antihypertensive medications. She noted that previous studies involving rodents “have shown beneficial effects [of BBB-crossing antihypertensive drugs] on cognition independent of their effects on blood pressure.”
The drugs’ exact mechanisms of action, however, remain elusive, according to Dr. Girouard, who offered several possible explanations, including amelioration of BBB disruption, brain inflammation, cerebral blood flow dysregulation, cholinergic dysfunction, and neurologic deficits. “Whether these mechanisms may explain Ho and colleagues’ observations remains to be established,” she added.
Andrea L. Schneider, MD, PhD, assistant professor of neurology at the University of Pennsylvania, Philadelphia, applauded the study, but ultimately suggested that more research is needed to impact clinical decision-making.
“The results of this important and well-done study suggest that further investigation into targeted mechanism-based approaches to selecting hypertension treatment agents, with a specific focus on cognitive outcomes, is warranted,” Dr. Schneider said in an interview. “Before changing clinical practice, further work is necessary to disentangle contributions of medication mechanism, comorbid vascular risk factors, and achieved blood pressure reduction, among others.”
The investigators disclosed support from the National Institutes of Health, the Alzheimer’s Association, the Waksman Foundation of Japan, and others. The interviewees reported no relevant conflicts of interest.
FROM HYPERTENSION
Potential first-in-class, targeted therapy for myasthenia gravis
(gMG), new research suggests. Results from the phase 3, randomized, placebo-controlled ADAPT trial showed that reduction in disease burden and improvement in strength and quality of life in patients with gMG were consistent across four MG-specific scales for those receiving the novel treatment. In addition, these benefits were observed early and were reproducible and durable, the researchers noted.
Efgartigimod is a “very rapidly acting drug relative to other treatments that may take 4, 6, sometimes 10 months before they start to work, and the side effect profile is much like placebo,” said principal investigator James Howard, Jr., MD, Distinguished Professor of Neuromuscular Disease, department of neurology, University of North Carolina at Chapel Hill.
The ADAPT results are “important for the MG community, and I am hopeful efgartigimod will provide a first-in-class targeted therapy that can be dosed in an individual way for people living with this chronic autoimmune disease,” Dr. Howard added in a news release.
The findings were published online June 17 in Lancet Neurology.
Targeted molecular therapy
The rare and chronic autoimmune neuromuscular disorder of gMG causes debilitating and potentially life-threatening muscle weakness and significantly impaired independence and quality of life. Most patients with gMG have immunoglobulin G (IgG) antibodies, which are most often directed against skeletal muscle nicotinic acetylcholine receptors.
Efgartigimod is an investigational antibody fragment designed to reduce pathogenic IgG antibodies and block the IgG recycling process in patients with gMG.
The novel agent binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels.
The ADAPT trial was conducted at 56 neuromuscular academic and community centers in 15 countries in North America, Europe, and Japan. The study included 167 adults with gMG, regardless of acetylcholine receptor antibody status. All had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (greater than 50% non-ocular) on a background of a stable dose of at least one MG drug.
For 26 weeks, 84 patients were randomly assigned to receive efgartigimod 10 mg/kg and 83 to receive matching placebo. Both treatments were administered as four infusions per cycle at one infusion per week. The process was repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle.
ADAPT was designed to allow an individualized treatment approach with an initial treatment cycle followed by a variable number of subsequent treatment cycles, the investigators noted.
Primary endpoint met
The primary efficacy endpoint was number of acetylcholine receptor antibody-positive (AChR-Ab+) patients who achieved a clinically meaningful response on the MG-ADL score. This was defined as at least a 2-point improvement from baseline for 4 or more consecutive weeks. Forty-four (68%) of 65 AChR-Ab+ patients treated with efgartigimod met this endpoint versus 19 (30%) of 64 patients treated with placebo (odds ratio, 4.95; 95% confidence interval, 2.21-11.53; P < .0001).
Many of the patients treated with efgartigimod showed improvement “beyond the clinically meaningful threshold, achieving up to 9-point reductions in MG-ADL,” the investigators reported. In addition, 40% of the efgartigimod group attained an MG-ADL score of 0 or 1 (minimal symptom expression) in cycle 1 versus 11% of the placebo group (P < .0001).
Nearly two-thirds (63%) of AChR-Ab+ patients responded to the first cycle of efgartigimod, and most of these patients (83%) responded to treatment within the first 2 weeks. Among the AChR-Ab+ participants who responded to efgartigimod in cycle 1, the duration of responder status was 6 to 7 weeks in 32% of patients, 8 to 11 weeks in 23% of patients, and 12 weeks or more in 34% of patients.
Safety profile
“Some patients never required retreatment over the 26-week period that they were under observation,” Dr. Howard said. “Patients want to be individuals. They don’t want to be assigned to a regimented therapy, and I think these results show that this therapy can be tailored to the individual patient, rather than simply giving it to them in a cookbook fashion,” he added.
The safety profile of efgartigimod was comparable to placebo. Most adverse events were mild or moderate in severity. The most commonly reported adverse events were headache, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, and urinary tract infection.
Four (5%) efgartigimod-treated patients had a serious adverse event, which included thrombocytosis, rectal adenocarcinoma, worsening MG, and depression.
The novel agent is currently under review with the U.S. Food and Drug Administration for the treatment of gMG, with a Prescription Drug User Fee Act target action date of Dec. 17. If approved, it would become the first FDA-approved FcRn antagonist.
Expanding therapeutic landscape
In a linked commentary, Shigeaki Suzuki, MD, PhD, department of neurology, Keio University School of Medicine, Tokyo, noted that the therapeutic landscape for patients with MG is “expanding year by year,” with several additional complement inhibitors and FcRn antagonists now in phase 3 testing.
“Biological drugs should be preferentially used as the treatment for patients with refractory myasthenia gravis, although the definition of refractory myasthenia gravis is different depending on the criteria used,” Dr. Suzuki wrote.
He noted that when “cost-effectiveness is not taken into account, targeted molecular therapy might be used widely” in patients with MG.
“Risks of myasthenic exacerbation and crises should be substantially decreased, particularly in patients with refractory myasthenia gravis,” Dr. Suzuki added.
The ADAPT study was supported by argenx. Dr. Howard has reported receiving research support from argenx, Alexion Pharmaceuticals, the Centers for Disease Control and Prevention, the Muscular Dystrophy Association, the National Institutes of Health, Patient-Centered Outcomes Research Institute, and Ra Pharmaceuticals; honoraria from argenx, Alexion, Immunovant, Ra, Regeneron Pharmaceuticals, and Viela Bio; and nonfinancial support from argenx, Alexion, Ra, and Toleranzia. Disclosures for the other investigators are listed in the original article. Dr. Suzuki has reported relationships with Alexion Pharmaceuticals, Japan Blood Products Organization, and Asahi Kasei Medical.
A version of this article first appeared on Medscape.com.
(gMG), new research suggests. Results from the phase 3, randomized, placebo-controlled ADAPT trial showed that reduction in disease burden and improvement in strength and quality of life in patients with gMG were consistent across four MG-specific scales for those receiving the novel treatment. In addition, these benefits were observed early and were reproducible and durable, the researchers noted.
Efgartigimod is a “very rapidly acting drug relative to other treatments that may take 4, 6, sometimes 10 months before they start to work, and the side effect profile is much like placebo,” said principal investigator James Howard, Jr., MD, Distinguished Professor of Neuromuscular Disease, department of neurology, University of North Carolina at Chapel Hill.
The ADAPT results are “important for the MG community, and I am hopeful efgartigimod will provide a first-in-class targeted therapy that can be dosed in an individual way for people living with this chronic autoimmune disease,” Dr. Howard added in a news release.
The findings were published online June 17 in Lancet Neurology.
Targeted molecular therapy
The rare and chronic autoimmune neuromuscular disorder of gMG causes debilitating and potentially life-threatening muscle weakness and significantly impaired independence and quality of life. Most patients with gMG have immunoglobulin G (IgG) antibodies, which are most often directed against skeletal muscle nicotinic acetylcholine receptors.
Efgartigimod is an investigational antibody fragment designed to reduce pathogenic IgG antibodies and block the IgG recycling process in patients with gMG.
The novel agent binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels.
The ADAPT trial was conducted at 56 neuromuscular academic and community centers in 15 countries in North America, Europe, and Japan. The study included 167 adults with gMG, regardless of acetylcholine receptor antibody status. All had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (greater than 50% non-ocular) on a background of a stable dose of at least one MG drug.
For 26 weeks, 84 patients were randomly assigned to receive efgartigimod 10 mg/kg and 83 to receive matching placebo. Both treatments were administered as four infusions per cycle at one infusion per week. The process was repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle.
ADAPT was designed to allow an individualized treatment approach with an initial treatment cycle followed by a variable number of subsequent treatment cycles, the investigators noted.
Primary endpoint met
The primary efficacy endpoint was number of acetylcholine receptor antibody-positive (AChR-Ab+) patients who achieved a clinically meaningful response on the MG-ADL score. This was defined as at least a 2-point improvement from baseline for 4 or more consecutive weeks. Forty-four (68%) of 65 AChR-Ab+ patients treated with efgartigimod met this endpoint versus 19 (30%) of 64 patients treated with placebo (odds ratio, 4.95; 95% confidence interval, 2.21-11.53; P < .0001).
Many of the patients treated with efgartigimod showed improvement “beyond the clinically meaningful threshold, achieving up to 9-point reductions in MG-ADL,” the investigators reported. In addition, 40% of the efgartigimod group attained an MG-ADL score of 0 or 1 (minimal symptom expression) in cycle 1 versus 11% of the placebo group (P < .0001).
Nearly two-thirds (63%) of AChR-Ab+ patients responded to the first cycle of efgartigimod, and most of these patients (83%) responded to treatment within the first 2 weeks. Among the AChR-Ab+ participants who responded to efgartigimod in cycle 1, the duration of responder status was 6 to 7 weeks in 32% of patients, 8 to 11 weeks in 23% of patients, and 12 weeks or more in 34% of patients.
Safety profile
“Some patients never required retreatment over the 26-week period that they were under observation,” Dr. Howard said. “Patients want to be individuals. They don’t want to be assigned to a regimented therapy, and I think these results show that this therapy can be tailored to the individual patient, rather than simply giving it to them in a cookbook fashion,” he added.
The safety profile of efgartigimod was comparable to placebo. Most adverse events were mild or moderate in severity. The most commonly reported adverse events were headache, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, and urinary tract infection.
Four (5%) efgartigimod-treated patients had a serious adverse event, which included thrombocytosis, rectal adenocarcinoma, worsening MG, and depression.
The novel agent is currently under review with the U.S. Food and Drug Administration for the treatment of gMG, with a Prescription Drug User Fee Act target action date of Dec. 17. If approved, it would become the first FDA-approved FcRn antagonist.
Expanding therapeutic landscape
In a linked commentary, Shigeaki Suzuki, MD, PhD, department of neurology, Keio University School of Medicine, Tokyo, noted that the therapeutic landscape for patients with MG is “expanding year by year,” with several additional complement inhibitors and FcRn antagonists now in phase 3 testing.
“Biological drugs should be preferentially used as the treatment for patients with refractory myasthenia gravis, although the definition of refractory myasthenia gravis is different depending on the criteria used,” Dr. Suzuki wrote.
He noted that when “cost-effectiveness is not taken into account, targeted molecular therapy might be used widely” in patients with MG.
“Risks of myasthenic exacerbation and crises should be substantially decreased, particularly in patients with refractory myasthenia gravis,” Dr. Suzuki added.
The ADAPT study was supported by argenx. Dr. Howard has reported receiving research support from argenx, Alexion Pharmaceuticals, the Centers for Disease Control and Prevention, the Muscular Dystrophy Association, the National Institutes of Health, Patient-Centered Outcomes Research Institute, and Ra Pharmaceuticals; honoraria from argenx, Alexion, Immunovant, Ra, Regeneron Pharmaceuticals, and Viela Bio; and nonfinancial support from argenx, Alexion, Ra, and Toleranzia. Disclosures for the other investigators are listed in the original article. Dr. Suzuki has reported relationships with Alexion Pharmaceuticals, Japan Blood Products Organization, and Asahi Kasei Medical.
A version of this article first appeared on Medscape.com.
(gMG), new research suggests. Results from the phase 3, randomized, placebo-controlled ADAPT trial showed that reduction in disease burden and improvement in strength and quality of life in patients with gMG were consistent across four MG-specific scales for those receiving the novel treatment. In addition, these benefits were observed early and were reproducible and durable, the researchers noted.
Efgartigimod is a “very rapidly acting drug relative to other treatments that may take 4, 6, sometimes 10 months before they start to work, and the side effect profile is much like placebo,” said principal investigator James Howard, Jr., MD, Distinguished Professor of Neuromuscular Disease, department of neurology, University of North Carolina at Chapel Hill.
The ADAPT results are “important for the MG community, and I am hopeful efgartigimod will provide a first-in-class targeted therapy that can be dosed in an individual way for people living with this chronic autoimmune disease,” Dr. Howard added in a news release.
The findings were published online June 17 in Lancet Neurology.
Targeted molecular therapy
The rare and chronic autoimmune neuromuscular disorder of gMG causes debilitating and potentially life-threatening muscle weakness and significantly impaired independence and quality of life. Most patients with gMG have immunoglobulin G (IgG) antibodies, which are most often directed against skeletal muscle nicotinic acetylcholine receptors.
Efgartigimod is an investigational antibody fragment designed to reduce pathogenic IgG antibodies and block the IgG recycling process in patients with gMG.
The novel agent binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels.
The ADAPT trial was conducted at 56 neuromuscular academic and community centers in 15 countries in North America, Europe, and Japan. The study included 167 adults with gMG, regardless of acetylcholine receptor antibody status. All had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (greater than 50% non-ocular) on a background of a stable dose of at least one MG drug.
For 26 weeks, 84 patients were randomly assigned to receive efgartigimod 10 mg/kg and 83 to receive matching placebo. Both treatments were administered as four infusions per cycle at one infusion per week. The process was repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle.
ADAPT was designed to allow an individualized treatment approach with an initial treatment cycle followed by a variable number of subsequent treatment cycles, the investigators noted.
Primary endpoint met
The primary efficacy endpoint was number of acetylcholine receptor antibody-positive (AChR-Ab+) patients who achieved a clinically meaningful response on the MG-ADL score. This was defined as at least a 2-point improvement from baseline for 4 or more consecutive weeks. Forty-four (68%) of 65 AChR-Ab+ patients treated with efgartigimod met this endpoint versus 19 (30%) of 64 patients treated with placebo (odds ratio, 4.95; 95% confidence interval, 2.21-11.53; P < .0001).
Many of the patients treated with efgartigimod showed improvement “beyond the clinically meaningful threshold, achieving up to 9-point reductions in MG-ADL,” the investigators reported. In addition, 40% of the efgartigimod group attained an MG-ADL score of 0 or 1 (minimal symptom expression) in cycle 1 versus 11% of the placebo group (P < .0001).
Nearly two-thirds (63%) of AChR-Ab+ patients responded to the first cycle of efgartigimod, and most of these patients (83%) responded to treatment within the first 2 weeks. Among the AChR-Ab+ participants who responded to efgartigimod in cycle 1, the duration of responder status was 6 to 7 weeks in 32% of patients, 8 to 11 weeks in 23% of patients, and 12 weeks or more in 34% of patients.
Safety profile
“Some patients never required retreatment over the 26-week period that they were under observation,” Dr. Howard said. “Patients want to be individuals. They don’t want to be assigned to a regimented therapy, and I think these results show that this therapy can be tailored to the individual patient, rather than simply giving it to them in a cookbook fashion,” he added.
The safety profile of efgartigimod was comparable to placebo. Most adverse events were mild or moderate in severity. The most commonly reported adverse events were headache, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, and urinary tract infection.
Four (5%) efgartigimod-treated patients had a serious adverse event, which included thrombocytosis, rectal adenocarcinoma, worsening MG, and depression.
The novel agent is currently under review with the U.S. Food and Drug Administration for the treatment of gMG, with a Prescription Drug User Fee Act target action date of Dec. 17. If approved, it would become the first FDA-approved FcRn antagonist.
Expanding therapeutic landscape
In a linked commentary, Shigeaki Suzuki, MD, PhD, department of neurology, Keio University School of Medicine, Tokyo, noted that the therapeutic landscape for patients with MG is “expanding year by year,” with several additional complement inhibitors and FcRn antagonists now in phase 3 testing.
“Biological drugs should be preferentially used as the treatment for patients with refractory myasthenia gravis, although the definition of refractory myasthenia gravis is different depending on the criteria used,” Dr. Suzuki wrote.
He noted that when “cost-effectiveness is not taken into account, targeted molecular therapy might be used widely” in patients with MG.
“Risks of myasthenic exacerbation and crises should be substantially decreased, particularly in patients with refractory myasthenia gravis,” Dr. Suzuki added.
The ADAPT study was supported by argenx. Dr. Howard has reported receiving research support from argenx, Alexion Pharmaceuticals, the Centers for Disease Control and Prevention, the Muscular Dystrophy Association, the National Institutes of Health, Patient-Centered Outcomes Research Institute, and Ra Pharmaceuticals; honoraria from argenx, Alexion, Immunovant, Ra, Regeneron Pharmaceuticals, and Viela Bio; and nonfinancial support from argenx, Alexion, Ra, and Toleranzia. Disclosures for the other investigators are listed in the original article. Dr. Suzuki has reported relationships with Alexion Pharmaceuticals, Japan Blood Products Organization, and Asahi Kasei Medical.
A version of this article first appeared on Medscape.com.
From Lancet Neurology
How dreams might prepare you for what’s next
What you experience in your dreams might feel random and disjointed, but that chaos during sleep might serve a function, according to Erin Wamsley, PhD, an associate professor of psychology and neuroscience at Furman University in Greenville, S.C. In fact, evidence uncovered by Dr. Wamsley and associates suggests that
Previous research and anecdotal evidence have shown that dreams use fragments of past experiences, Dr. Wamsley explained. While studying dreams, her team found that the mind is using select fragments of past experiences to prepare for a known upcoming event.
“This is new evidence that dreams reflect a memory-processing function,” said Dr. Wamsley, who presented the work at the virtual annual meeting of the Associated Professional Sleep Societies.
Some high performers already use past experiences to excel in future events. For instance, Michael Phelps, the most decorated Olympic swimmer, with 28 medals, would “mentally rehearse” his swims for up to 2 hours per day, according to his coach, Bob Bowman.
Using sleep to strengthen this process is an exciting prospect that scientists have been eager to figure out, said Allison Brager, PhD, director of human performance at the U.S. Army Warrior Fitness Training Center. Deep REM sleep can lead to improved learning and memory, she said. “So, hypothetically, better dreams mean better sleep, and that equals better performance.”
For their research, Dr. Wamsley’s team hooked 48 students up to a polysomnography machine to measure sleep cycles and how often they were in a deep REM sleep. The students who took part in the study spent the night in a sleep lab.
The students were woken up multiple times during the night and asked to report what they were dreaming about.
In the morning, they were given their reports and asked to identify familiar features or potential sources for particular dreams. More than half the dreams were tied to a memory the students recalled. One-quarter of the dreams were related to specific upcoming events the students reported. And about 40% of the dreams with a future event in them also included memories of past experiences. This was more common the longer the students dreamed, the scientists explained.
And this was also more common later in the night, possibly because the dreamer is closer to waking and the anticipated event is approaching, Dr. Wamsley said.
Studying dreams is a tricky, subjective business and not always taken as seriously as other aspects of sleep and neuroscience because it involves questions of human consciousness itself, said Erik Hoel, PhD, a research assistant professor of neuroscience at Tufts University in Medford, Mass.
In a recent report published in Patterns, he suggested that our weirdest dreams help our brains process our day-to-day experiences in a way that enables deeper learning.
“This type of research is challenged by the method,” Dr. Hoel said.
In the Wamsley study, “waking people up from a deep sleep and asking them to recollect their dream content will only get you part of the experience because it fades so quickly.” That said, the value of connecting what happens as a result could be meaningful, he noted. For example, study participants could be asked whether their future event went as planned and whether they think the outcome was related to how well they “prepared” in their dreams.
Even then, it would still be a subjective analysis. But going in those directions might lead to meaningful new training, Dr. Hoel said.
And training yourself to recall only specific memories right before sleep might prepare your mind in a focused way for certain events, from giving a presentation to having a difficult conversation with someone, or maybe even winning at the Olympics.
A version of this article first appeared on WebMD.com.
What you experience in your dreams might feel random and disjointed, but that chaos during sleep might serve a function, according to Erin Wamsley, PhD, an associate professor of psychology and neuroscience at Furman University in Greenville, S.C. In fact, evidence uncovered by Dr. Wamsley and associates suggests that
Previous research and anecdotal evidence have shown that dreams use fragments of past experiences, Dr. Wamsley explained. While studying dreams, her team found that the mind is using select fragments of past experiences to prepare for a known upcoming event.
“This is new evidence that dreams reflect a memory-processing function,” said Dr. Wamsley, who presented the work at the virtual annual meeting of the Associated Professional Sleep Societies.
Some high performers already use past experiences to excel in future events. For instance, Michael Phelps, the most decorated Olympic swimmer, with 28 medals, would “mentally rehearse” his swims for up to 2 hours per day, according to his coach, Bob Bowman.
Using sleep to strengthen this process is an exciting prospect that scientists have been eager to figure out, said Allison Brager, PhD, director of human performance at the U.S. Army Warrior Fitness Training Center. Deep REM sleep can lead to improved learning and memory, she said. “So, hypothetically, better dreams mean better sleep, and that equals better performance.”
For their research, Dr. Wamsley’s team hooked 48 students up to a polysomnography machine to measure sleep cycles and how often they were in a deep REM sleep. The students who took part in the study spent the night in a sleep lab.
The students were woken up multiple times during the night and asked to report what they were dreaming about.
In the morning, they were given their reports and asked to identify familiar features or potential sources for particular dreams. More than half the dreams were tied to a memory the students recalled. One-quarter of the dreams were related to specific upcoming events the students reported. And about 40% of the dreams with a future event in them also included memories of past experiences. This was more common the longer the students dreamed, the scientists explained.
And this was also more common later in the night, possibly because the dreamer is closer to waking and the anticipated event is approaching, Dr. Wamsley said.
Studying dreams is a tricky, subjective business and not always taken as seriously as other aspects of sleep and neuroscience because it involves questions of human consciousness itself, said Erik Hoel, PhD, a research assistant professor of neuroscience at Tufts University in Medford, Mass.
In a recent report published in Patterns, he suggested that our weirdest dreams help our brains process our day-to-day experiences in a way that enables deeper learning.
“This type of research is challenged by the method,” Dr. Hoel said.
In the Wamsley study, “waking people up from a deep sleep and asking them to recollect their dream content will only get you part of the experience because it fades so quickly.” That said, the value of connecting what happens as a result could be meaningful, he noted. For example, study participants could be asked whether their future event went as planned and whether they think the outcome was related to how well they “prepared” in their dreams.
Even then, it would still be a subjective analysis. But going in those directions might lead to meaningful new training, Dr. Hoel said.
And training yourself to recall only specific memories right before sleep might prepare your mind in a focused way for certain events, from giving a presentation to having a difficult conversation with someone, or maybe even winning at the Olympics.
A version of this article first appeared on WebMD.com.
What you experience in your dreams might feel random and disjointed, but that chaos during sleep might serve a function, according to Erin Wamsley, PhD, an associate professor of psychology and neuroscience at Furman University in Greenville, S.C. In fact, evidence uncovered by Dr. Wamsley and associates suggests that
Previous research and anecdotal evidence have shown that dreams use fragments of past experiences, Dr. Wamsley explained. While studying dreams, her team found that the mind is using select fragments of past experiences to prepare for a known upcoming event.
“This is new evidence that dreams reflect a memory-processing function,” said Dr. Wamsley, who presented the work at the virtual annual meeting of the Associated Professional Sleep Societies.
Some high performers already use past experiences to excel in future events. For instance, Michael Phelps, the most decorated Olympic swimmer, with 28 medals, would “mentally rehearse” his swims for up to 2 hours per day, according to his coach, Bob Bowman.
Using sleep to strengthen this process is an exciting prospect that scientists have been eager to figure out, said Allison Brager, PhD, director of human performance at the U.S. Army Warrior Fitness Training Center. Deep REM sleep can lead to improved learning and memory, she said. “So, hypothetically, better dreams mean better sleep, and that equals better performance.”
For their research, Dr. Wamsley’s team hooked 48 students up to a polysomnography machine to measure sleep cycles and how often they were in a deep REM sleep. The students who took part in the study spent the night in a sleep lab.
The students were woken up multiple times during the night and asked to report what they were dreaming about.
In the morning, they were given their reports and asked to identify familiar features or potential sources for particular dreams. More than half the dreams were tied to a memory the students recalled. One-quarter of the dreams were related to specific upcoming events the students reported. And about 40% of the dreams with a future event in them also included memories of past experiences. This was more common the longer the students dreamed, the scientists explained.
And this was also more common later in the night, possibly because the dreamer is closer to waking and the anticipated event is approaching, Dr. Wamsley said.
Studying dreams is a tricky, subjective business and not always taken as seriously as other aspects of sleep and neuroscience because it involves questions of human consciousness itself, said Erik Hoel, PhD, a research assistant professor of neuroscience at Tufts University in Medford, Mass.
In a recent report published in Patterns, he suggested that our weirdest dreams help our brains process our day-to-day experiences in a way that enables deeper learning.
“This type of research is challenged by the method,” Dr. Hoel said.
In the Wamsley study, “waking people up from a deep sleep and asking them to recollect their dream content will only get you part of the experience because it fades so quickly.” That said, the value of connecting what happens as a result could be meaningful, he noted. For example, study participants could be asked whether their future event went as planned and whether they think the outcome was related to how well they “prepared” in their dreams.
Even then, it would still be a subjective analysis. But going in those directions might lead to meaningful new training, Dr. Hoel said.
And training yourself to recall only specific memories right before sleep might prepare your mind in a focused way for certain events, from giving a presentation to having a difficult conversation with someone, or maybe even winning at the Olympics.
A version of this article first appeared on WebMD.com.
FROM SLEEP 2021
A Veteran Presenting With Shortness of Breath, Cough, and Leukocytosis
Case Presentation: A 62-year-old male presented with shortness of breath and a cough productive of green sputum. He had a history of hyperlipidemia, posttraumatic stress disorder, bipolar disorder, obstructive sleep apnea, and a 50 pack-year history of smoking. His medications included prazosin, melatonin, lithium, and gabapentin. He also had a significant exposure history including asbestos and chemical paints following his leave from the military. At the initial evaluation, laboratory work revealed a leukocytosis with white blood cell (WBC) count 20 k/cm3and otherwise normal transaminases, albumin, and electrolytes. A chest X-ray revealed a new left hilar mass.
►Manisha Apte, MD, Chief Medical Resident, VA Boston Healthcare System (VABHS) and Boston Medical Center (BMC): To work up his new left hilar mass, a computed tomography (CT) of the chest was ordered (Figure 1), which revealed an apical left lower lobe mass extending into the left hilum encasing part of the ascending aorta. Enlarged mediastinal subcentimeter paratracheal and superior mediastinal lymph nodes also were identified and the pattern raised the concern for lymphangitic carcinomatosis. Dr. Fine, what do you make of the CT findings?
► Alan Fine, MD, Section of Pulmonary and Critical Care, VABHS and Professor of Medicine, Boston University School of Medicine: This mass had irregular edges with septal thickening, which may be why there was a concern for lymphangitic spread. There were no clear tissue planes to see if this process was invading the mediastinum. The mass was irregular, a single lesion, and proximal, making it consistent with a lung cancer. In fact, with his history of smoking, asbestos exposure, the numbers 1 to 10 diagnoses were lung cancer. The lack of demarcation of tissue planes supports this. There are some infections, classically actinomycosis, that do cross and invade anatomical barriers.1 But this looked like a primary lung cancer.
► Dr. Apte: The patient was referred to a pulmonologist where an additional history of night sweats and weight loss were noted. Dr. Fine, we have a patient with a newly identified lung mass, and while we have reason to suspect malignancy as you have already noted, there are many other etiologies to consider, including infections (histoplasmosis, cryptococcosis, bacterial abscess), inflammatory processes (sarcoidosis, rheumatoid nodule) and vasculitis (granulomatosis with polyangiitis). What should be the next step taken to make a diagnosis?
►Dr. Fine: For cancer specifically, we would like to both stage and make a diagnosis with one procedure. That’s part of the utility of a positron emission tomography (PET) scan: We can see lymph node involvement and stage the cancer. We must consider the patient’s comorbidities and the location of the lesion (ie, is it amenable to needle biopsy?). In this case, there are enlarged mediastinal lymph nodes, so one could perform a bronchoscopy with endobronchial ultrasound, which is a relatively noninvasive way to sample the lymph nodes to ideally stage and make a diagnosis as safely as possible. If we are considering infection, needle aspiration is not as sensitive.2
► Dr. Apte: The patient underwent a PET CT, which redemonstrated the lung mass with a loss of aortic fat plane suspicious for aortic involvement as well as lymph nodes in levels 7 and 8 that were concerning for malignancy. Subsequent bronchoscopy with biopsy and endobronchial ultrasound did not show evidence of malignancy; washing and brushing from the mass and lymph node specimens did not identify malignant cells. Benign respiratory mucosa with mild chronic inflammation was noted. Dr. Fine, given the nonspecific findings on the PET scan, negative findings on our bronchoscopy, and a negative biopsy, should we be satisfied that we have ruled out cancer?
► Dr. Fine: No, bronchoscopy has its limitations. It’s highly sensitive to the diagnosis of malignancy if you can see an endobronchial lesion, but we did not see one here. You can only go so far with the scope, and it’s not uncommon for us not to be able to make the diagnosis with bronchoscopy. Malignancy is still the most likely diagnosis, and we need to work this up further. I would perform another biopsy.
►Dr. Apte: Four weeks later, the patient presented with continued shortness of breath, fatigue, and fever. A repeat chest CT showed an opacity suggestive of pneumonia. Given the continued concern for cancer a CT-guided needle biopsy was performed and was once again negative for malignancy. The decision was made to pursue a video-assisted thorascopic surgery (VATS). Following the VATS, the patient developed rigors, fever, and tachycardia with new atrial fibrillation. While being evaluated hypercalcemia was identified, with further workup revealing a low parathyroid hormone (PTH) and low PTH-related peptide. Dr. Fine, the presence of hypercalcemia and a new arrythmia raised the possibility of sarcoidosis. Could this be sarcoidosis?
►Dr. Fine: Sarcoidosis is one of the great masqueraders in medicine. There is a type of sarcoidosis called nodular sarcoidosis where you see masslike distribution in the lung, but generally there are multiple masses and so this presentation would be atypical.3 There is also a phenomenon called sarcoidal reactions usually in the presence of cancer. Again, one tends to see multiple tiny lesions in the lung. It is certainly on the differential, but I would consider it to be less likely than cancer. It is also relatively common to develop atrial fibrillation after manipulation from a lung surgery.4 The other possibility I am concerned about is whether the mass is invading the mediastinum and involving the pericardium.
►Dr. Apte: Results from the VATS biopsy once again returned negative for malignancy and instead showed signs of focal micro-abscesses, atypical pneumocytes, and prominent neutrophils. A diagnosis of acute fibrinous organizing pneumonia (AFOP) was offered. Dr. Fine, what is AFOP?
►Dr. Fine: This is the first case of AFOP I had seen and probably the first case many in our department have seen. This is a relatively new entity with limited reported cases in the literature and is a pathological diagnosis originally recorded in autopsies from patients at the National Institutes of Health.5,6 Given the complexity of the lesion, the diagnosis is difficult to make. Most commonly, AFOP is associated with other systemic entities, most commonly hematologic malignancies like lymphomas and leukemias. It has also been associated with vasculitis and certain drugs. The mechanism is poorly understood, and although pneumonia is a part of the term, this just implies there is inflammation of the lung (ie, pneumonitis).
► Dr. Apte: Given the association of AFOP with underlying hematologic malignancies, an emphasis was placed on another finding: the patient’s increasing WBC count. The total WBC count had been 20 k/cm3 at the time of his lung mass discovery but had increased to > 40 k/cm3 with a differential of neutrophils > 80%. Flow cytometry was negative, and his peripheral smear was read as normal. Dr. Gilbert, what might explain this patient’s leukocytosis?
►Gary Gilbert, MD, Section of Hematology and Oncology, VABHS and Associate Professor of Medicine, Harvard Medical School (HMS): This patient had an elevated WBC for 4 months. Initially, the cause was likely lithium as this is known to cause a leukocytosis.7 More recently, the total WBC had increased and there were a couple of other abnormalities: A consistently elevated absolute monocyte count and a markedly elevated mature neutrophil count. These findings are consistent with a leukemoid reaction (ie, a WBC count > 50,000/µL from causes other than leukemia). The question becomes what is this a leukemoid reaction in response to? Once we have excluded a lung malignancy (a well-known common cause of a leukemoid reaction) we must consider a clonal myeloproliferative disorder. This is particularly true because many things that cause a leukemoid reaction (eg, lobar pneumonia) do not cause a persistently elevated neutrophil count. That this patient does have a persistently elevated neutrophil count suggests something abnormal about the neutrophils themselves.
► Dr. Apte: A bone marrow biopsy was performed. Dr. Gilbert, can you comment on this patient’s bone marrow biopsy and whether a myeloproliferative disorder may have played a role in the marked leukocytosis?
► Dr. Gilbert: The bone marrow biopsy was hyperplastic with myeloid predominance and normal maturation in all lineages. A deep sequencing analysis demonstrated the absence of chromosomal abnormalities or genetic mutations that are associated with myeloproliferative disorders. This excludes the possibility of a myeloproliferative disorder.
► Dr. Apte: The patient was started on 60 mg of prednisone daily, which led to marked improvement in his symptoms. He was discharged in stable condition but presented again with abdominal pain. A complete blood count once again showed increased WBC and new thrombocytosis. A CT angiogram (CTA) showed the prior lung mass with new signs of central necrosis. In the abdomen, new splenic and renal infarct were identified, along with signs of multiple arterial thrombi in the abdomen and internal and external iliac vessel wall thickening. These findings were read as concerning for a medium vessel vasculitis. Dr. Kaur, what are some of the imaging findings you would expect to see in vasculitis, and what about this patient’s CT is consistent with a medium vessel vasculitis?
► Maneet Kaur, MD, Section of Rheumatology, VABHS: Vasculitis is inflammation of the vessel wall that can lead to vascular injury and activation of the coagulation cascade. Sometimes these findings can be seen on imaging with evidence of stenosis, microaneurysms, and thrombosis distal to the stenosis. The nomenclature of vasculitis is not simple and has been revised many times. Medium-vessel vasculitis does not just affect the medium vessels (eg, visceral arteries) but can overlap with distal large vessels and smaller cutaneous vessels.
The first thing that comes to mind in this case is polyarteritis nodosa (PAN), an immune complex-mediated medium vessel disease that can involve large and small vessels in muscle, nerve, and skin. It can also present with masses.
►Dr. Apte: To address the arterial thrombi seen on CTA, arterial-brachial indices were obtained and showed bilateral occlusive disease in his distal extremities; findings that could be explained by vasculitis. His VATS biopsy pathology was reviewed for signs of vasculitis. Dr. Huang, can you review these slides for us please?
►Qin Huang, MD, Department of Pathology and Laboratory Medicine, VABHS and Assistant Professor of Pathology, HMS: This patient had a history of smoking, and there are many black pigment-laden macrophages present in the lung tissue. There were areas of hemorrhage and fibrin deposition and an overall picture of organizing pneumonia. At a lower power, you can see neutrophils everywhere, some in the form of micro-abscesses. The arterial walls did not show signs of vasculitis (Figure 2). Based on the clinical information and radiology findings, we suspected an acute infection-related pneumonia or a primary lung malignancy causing obstruction pneumonia. We suggested a rebiopsy of the lung mass to rule out a primary lung malignancy.
► Dr. Apte: Given his CT findings, a serologic rheumatologic workup including antineutrophil cytoplasmic antibody, antinuclear antibody, and rheumatoid factors were sent and returned negative. The location of arterial wall inflammation on imaging made it unamenable for biopsy. The patient began to experience bilateral temporal pain, which raised the concern for a large vessel vasculitis, specifically giant cell arteritis. Bilateral temporal artery biopsies were obtained and were not suggestive of vasculitis. Dr. Kaur, we still do not have any serologic or biopsy confirmation to support a diagnosis of vasculitis. Can we still call this a vasculitis?
►Dr. Kaur: Few things can cause the picture that was seen radiographically. A few noninflammatory causes like fibromuscular dysplasia can cause both large and small vessel stenosis, but the elevations in erythrocyte sedimentation rate and C-reactive protein along with response to steroids makes these diagnoses unlikely. Sometimes we must make a clinical diagnosis for vasculitis based on the clinical picture, and I would feel comfortable treating this patient for vasculitis.
With that said, I remain concerned that this patient also has a malignancy. His WBC increased to > 70 k/cm3 and his calcium to > 13 mg/dL. These findings are hard to explain by vasculitis alone. There are cancer-associated vasculitis, and I suspect this is the explanation here.8 His temporal pain was pointing to large vessel involvement, so he could have an undifferentiated vasculitis.
► Dr. Apte: A decision was made to empirically treat with tocilizumab, an IL-6 receptor antagonist, for an undifferentiated autoimmune disease, in addition to tapering steroids. The patient underwent a second VATS, which again revealed AFOP but no signs of malignancy. Unfortunately, he developed multiple complications over the subsequent weeks and passed away. An autopsy was requested by family members and pathology from his lung mass was reviewed. (Figure 3). Dr. Huang, can you review these slides for us?
► Dr. Huang: The left lung mass at autopsy shows nests, poorly formed clusters, and individuals of malignant neoplastic nonkeratinizing squamous cells embedded in a desmoplastic stroma in the mass center, consistent with poorly differentiated squamous cell carcinoma, and a circumscribed area of residual subacute organizing pneumonia with abscess, granulomatous changes, and early fibrosis at the periphery of this mass.
►Dr. Apte: Based on autopsy findings, the final diagnosis was poorly differentiated squamous cell carcinoma associated with subacute organizing pneumonia and medium vessel vasculitis, which presented with a severe leukocytosis ultimately thought to be a leukemoid reaction from his lung cancer.
1. Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014;7:183-197. Published 2014 Jul 5. doi:10.2147/IDR.S39601
2. de Bazelaire C, Coffin A, Cohen-Zarade S, et al. CT-guided biopsies in lung infections in patients with haematological malignancies. Diagn Interv Imaging. 2013;94(2):202-215. doi:10.1016/j.diii.2012.12.008
3. Sweidan AJ, Singh NK, Stein A, Tanios M. Nodular sarcoidosis masquerading as cancer. Clin Med Insights Circ Respir Pulm Med. 2017;11:1179548417703123. Published 2017 Apr 12. doi:10.1177/1179548417703123
4. Bagheri R, Yousefi Y, Rezai R, Azemonfar V, Keshtan FG. Atrial fibrillation after lung surgery: incidence, underlying factors, and predictors. Kardiochir Torakochirurgia Pol. 2019;16(2):53-56. doi:10.5114/kitp.2019.86355
5. Lu J, Yin Q, Zha Y, et al. Acute fibrinous and organizing pneumonia: two case reports and literature review. BMC Pulm Med. 2019;19(1):141. Published 2019 Aug 5. doi:10.1186/s12890-019-0861-3
6. Beasley MB, Franks TJ, Galvin JR, Gochuico B, Travis WD. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med. 2002;126(9):1064-1070. doi:10.5858/2002-126-1064-AFAOP
7. Murphy DL, Goodwin FK, Bunney WE Jr. Leukocytosis during lithium treatment. Am J Psychiatry. 1971;127(11):1559-1561. doi:10.1176/ajp.127.11.1559
8. Fain O, Hamidou M, Cacoub P, et al. Vasculitides associated with malignancies: analysis of sixty patients. Arthritis Rheum. 2007;57(8):1473-1480. doi:10.1002/art.23085
Case Presentation: A 62-year-old male presented with shortness of breath and a cough productive of green sputum. He had a history of hyperlipidemia, posttraumatic stress disorder, bipolar disorder, obstructive sleep apnea, and a 50 pack-year history of smoking. His medications included prazosin, melatonin, lithium, and gabapentin. He also had a significant exposure history including asbestos and chemical paints following his leave from the military. At the initial evaluation, laboratory work revealed a leukocytosis with white blood cell (WBC) count 20 k/cm3and otherwise normal transaminases, albumin, and electrolytes. A chest X-ray revealed a new left hilar mass.
►Manisha Apte, MD, Chief Medical Resident, VA Boston Healthcare System (VABHS) and Boston Medical Center (BMC): To work up his new left hilar mass, a computed tomography (CT) of the chest was ordered (Figure 1), which revealed an apical left lower lobe mass extending into the left hilum encasing part of the ascending aorta. Enlarged mediastinal subcentimeter paratracheal and superior mediastinal lymph nodes also were identified and the pattern raised the concern for lymphangitic carcinomatosis. Dr. Fine, what do you make of the CT findings?
► Alan Fine, MD, Section of Pulmonary and Critical Care, VABHS and Professor of Medicine, Boston University School of Medicine: This mass had irregular edges with septal thickening, which may be why there was a concern for lymphangitic spread. There were no clear tissue planes to see if this process was invading the mediastinum. The mass was irregular, a single lesion, and proximal, making it consistent with a lung cancer. In fact, with his history of smoking, asbestos exposure, the numbers 1 to 10 diagnoses were lung cancer. The lack of demarcation of tissue planes supports this. There are some infections, classically actinomycosis, that do cross and invade anatomical barriers.1 But this looked like a primary lung cancer.
► Dr. Apte: The patient was referred to a pulmonologist where an additional history of night sweats and weight loss were noted. Dr. Fine, we have a patient with a newly identified lung mass, and while we have reason to suspect malignancy as you have already noted, there are many other etiologies to consider, including infections (histoplasmosis, cryptococcosis, bacterial abscess), inflammatory processes (sarcoidosis, rheumatoid nodule) and vasculitis (granulomatosis with polyangiitis). What should be the next step taken to make a diagnosis?
►Dr. Fine: For cancer specifically, we would like to both stage and make a diagnosis with one procedure. That’s part of the utility of a positron emission tomography (PET) scan: We can see lymph node involvement and stage the cancer. We must consider the patient’s comorbidities and the location of the lesion (ie, is it amenable to needle biopsy?). In this case, there are enlarged mediastinal lymph nodes, so one could perform a bronchoscopy with endobronchial ultrasound, which is a relatively noninvasive way to sample the lymph nodes to ideally stage and make a diagnosis as safely as possible. If we are considering infection, needle aspiration is not as sensitive.2
► Dr. Apte: The patient underwent a PET CT, which redemonstrated the lung mass with a loss of aortic fat plane suspicious for aortic involvement as well as lymph nodes in levels 7 and 8 that were concerning for malignancy. Subsequent bronchoscopy with biopsy and endobronchial ultrasound did not show evidence of malignancy; washing and brushing from the mass and lymph node specimens did not identify malignant cells. Benign respiratory mucosa with mild chronic inflammation was noted. Dr. Fine, given the nonspecific findings on the PET scan, negative findings on our bronchoscopy, and a negative biopsy, should we be satisfied that we have ruled out cancer?
► Dr. Fine: No, bronchoscopy has its limitations. It’s highly sensitive to the diagnosis of malignancy if you can see an endobronchial lesion, but we did not see one here. You can only go so far with the scope, and it’s not uncommon for us not to be able to make the diagnosis with bronchoscopy. Malignancy is still the most likely diagnosis, and we need to work this up further. I would perform another biopsy.
►Dr. Apte: Four weeks later, the patient presented with continued shortness of breath, fatigue, and fever. A repeat chest CT showed an opacity suggestive of pneumonia. Given the continued concern for cancer a CT-guided needle biopsy was performed and was once again negative for malignancy. The decision was made to pursue a video-assisted thorascopic surgery (VATS). Following the VATS, the patient developed rigors, fever, and tachycardia with new atrial fibrillation. While being evaluated hypercalcemia was identified, with further workup revealing a low parathyroid hormone (PTH) and low PTH-related peptide. Dr. Fine, the presence of hypercalcemia and a new arrythmia raised the possibility of sarcoidosis. Could this be sarcoidosis?
►Dr. Fine: Sarcoidosis is one of the great masqueraders in medicine. There is a type of sarcoidosis called nodular sarcoidosis where you see masslike distribution in the lung, but generally there are multiple masses and so this presentation would be atypical.3 There is also a phenomenon called sarcoidal reactions usually in the presence of cancer. Again, one tends to see multiple tiny lesions in the lung. It is certainly on the differential, but I would consider it to be less likely than cancer. It is also relatively common to develop atrial fibrillation after manipulation from a lung surgery.4 The other possibility I am concerned about is whether the mass is invading the mediastinum and involving the pericardium.
►Dr. Apte: Results from the VATS biopsy once again returned negative for malignancy and instead showed signs of focal micro-abscesses, atypical pneumocytes, and prominent neutrophils. A diagnosis of acute fibrinous organizing pneumonia (AFOP) was offered. Dr. Fine, what is AFOP?
►Dr. Fine: This is the first case of AFOP I had seen and probably the first case many in our department have seen. This is a relatively new entity with limited reported cases in the literature and is a pathological diagnosis originally recorded in autopsies from patients at the National Institutes of Health.5,6 Given the complexity of the lesion, the diagnosis is difficult to make. Most commonly, AFOP is associated with other systemic entities, most commonly hematologic malignancies like lymphomas and leukemias. It has also been associated with vasculitis and certain drugs. The mechanism is poorly understood, and although pneumonia is a part of the term, this just implies there is inflammation of the lung (ie, pneumonitis).
► Dr. Apte: Given the association of AFOP with underlying hematologic malignancies, an emphasis was placed on another finding: the patient’s increasing WBC count. The total WBC count had been 20 k/cm3 at the time of his lung mass discovery but had increased to > 40 k/cm3 with a differential of neutrophils > 80%. Flow cytometry was negative, and his peripheral smear was read as normal. Dr. Gilbert, what might explain this patient’s leukocytosis?
►Gary Gilbert, MD, Section of Hematology and Oncology, VABHS and Associate Professor of Medicine, Harvard Medical School (HMS): This patient had an elevated WBC for 4 months. Initially, the cause was likely lithium as this is known to cause a leukocytosis.7 More recently, the total WBC had increased and there were a couple of other abnormalities: A consistently elevated absolute monocyte count and a markedly elevated mature neutrophil count. These findings are consistent with a leukemoid reaction (ie, a WBC count > 50,000/µL from causes other than leukemia). The question becomes what is this a leukemoid reaction in response to? Once we have excluded a lung malignancy (a well-known common cause of a leukemoid reaction) we must consider a clonal myeloproliferative disorder. This is particularly true because many things that cause a leukemoid reaction (eg, lobar pneumonia) do not cause a persistently elevated neutrophil count. That this patient does have a persistently elevated neutrophil count suggests something abnormal about the neutrophils themselves.
► Dr. Apte: A bone marrow biopsy was performed. Dr. Gilbert, can you comment on this patient’s bone marrow biopsy and whether a myeloproliferative disorder may have played a role in the marked leukocytosis?
► Dr. Gilbert: The bone marrow biopsy was hyperplastic with myeloid predominance and normal maturation in all lineages. A deep sequencing analysis demonstrated the absence of chromosomal abnormalities or genetic mutations that are associated with myeloproliferative disorders. This excludes the possibility of a myeloproliferative disorder.
► Dr. Apte: The patient was started on 60 mg of prednisone daily, which led to marked improvement in his symptoms. He was discharged in stable condition but presented again with abdominal pain. A complete blood count once again showed increased WBC and new thrombocytosis. A CT angiogram (CTA) showed the prior lung mass with new signs of central necrosis. In the abdomen, new splenic and renal infarct were identified, along with signs of multiple arterial thrombi in the abdomen and internal and external iliac vessel wall thickening. These findings were read as concerning for a medium vessel vasculitis. Dr. Kaur, what are some of the imaging findings you would expect to see in vasculitis, and what about this patient’s CT is consistent with a medium vessel vasculitis?
► Maneet Kaur, MD, Section of Rheumatology, VABHS: Vasculitis is inflammation of the vessel wall that can lead to vascular injury and activation of the coagulation cascade. Sometimes these findings can be seen on imaging with evidence of stenosis, microaneurysms, and thrombosis distal to the stenosis. The nomenclature of vasculitis is not simple and has been revised many times. Medium-vessel vasculitis does not just affect the medium vessels (eg, visceral arteries) but can overlap with distal large vessels and smaller cutaneous vessels.
The first thing that comes to mind in this case is polyarteritis nodosa (PAN), an immune complex-mediated medium vessel disease that can involve large and small vessels in muscle, nerve, and skin. It can also present with masses.
►Dr. Apte: To address the arterial thrombi seen on CTA, arterial-brachial indices were obtained and showed bilateral occlusive disease in his distal extremities; findings that could be explained by vasculitis. His VATS biopsy pathology was reviewed for signs of vasculitis. Dr. Huang, can you review these slides for us please?
►Qin Huang, MD, Department of Pathology and Laboratory Medicine, VABHS and Assistant Professor of Pathology, HMS: This patient had a history of smoking, and there are many black pigment-laden macrophages present in the lung tissue. There were areas of hemorrhage and fibrin deposition and an overall picture of organizing pneumonia. At a lower power, you can see neutrophils everywhere, some in the form of micro-abscesses. The arterial walls did not show signs of vasculitis (Figure 2). Based on the clinical information and radiology findings, we suspected an acute infection-related pneumonia or a primary lung malignancy causing obstruction pneumonia. We suggested a rebiopsy of the lung mass to rule out a primary lung malignancy.
► Dr. Apte: Given his CT findings, a serologic rheumatologic workup including antineutrophil cytoplasmic antibody, antinuclear antibody, and rheumatoid factors were sent and returned negative. The location of arterial wall inflammation on imaging made it unamenable for biopsy. The patient began to experience bilateral temporal pain, which raised the concern for a large vessel vasculitis, specifically giant cell arteritis. Bilateral temporal artery biopsies were obtained and were not suggestive of vasculitis. Dr. Kaur, we still do not have any serologic or biopsy confirmation to support a diagnosis of vasculitis. Can we still call this a vasculitis?
►Dr. Kaur: Few things can cause the picture that was seen radiographically. A few noninflammatory causes like fibromuscular dysplasia can cause both large and small vessel stenosis, but the elevations in erythrocyte sedimentation rate and C-reactive protein along with response to steroids makes these diagnoses unlikely. Sometimes we must make a clinical diagnosis for vasculitis based on the clinical picture, and I would feel comfortable treating this patient for vasculitis.
With that said, I remain concerned that this patient also has a malignancy. His WBC increased to > 70 k/cm3 and his calcium to > 13 mg/dL. These findings are hard to explain by vasculitis alone. There are cancer-associated vasculitis, and I suspect this is the explanation here.8 His temporal pain was pointing to large vessel involvement, so he could have an undifferentiated vasculitis.
► Dr. Apte: A decision was made to empirically treat with tocilizumab, an IL-6 receptor antagonist, for an undifferentiated autoimmune disease, in addition to tapering steroids. The patient underwent a second VATS, which again revealed AFOP but no signs of malignancy. Unfortunately, he developed multiple complications over the subsequent weeks and passed away. An autopsy was requested by family members and pathology from his lung mass was reviewed. (Figure 3). Dr. Huang, can you review these slides for us?
► Dr. Huang: The left lung mass at autopsy shows nests, poorly formed clusters, and individuals of malignant neoplastic nonkeratinizing squamous cells embedded in a desmoplastic stroma in the mass center, consistent with poorly differentiated squamous cell carcinoma, and a circumscribed area of residual subacute organizing pneumonia with abscess, granulomatous changes, and early fibrosis at the periphery of this mass.
►Dr. Apte: Based on autopsy findings, the final diagnosis was poorly differentiated squamous cell carcinoma associated with subacute organizing pneumonia and medium vessel vasculitis, which presented with a severe leukocytosis ultimately thought to be a leukemoid reaction from his lung cancer.
Case Presentation: A 62-year-old male presented with shortness of breath and a cough productive of green sputum. He had a history of hyperlipidemia, posttraumatic stress disorder, bipolar disorder, obstructive sleep apnea, and a 50 pack-year history of smoking. His medications included prazosin, melatonin, lithium, and gabapentin. He also had a significant exposure history including asbestos and chemical paints following his leave from the military. At the initial evaluation, laboratory work revealed a leukocytosis with white blood cell (WBC) count 20 k/cm3and otherwise normal transaminases, albumin, and electrolytes. A chest X-ray revealed a new left hilar mass.
►Manisha Apte, MD, Chief Medical Resident, VA Boston Healthcare System (VABHS) and Boston Medical Center (BMC): To work up his new left hilar mass, a computed tomography (CT) of the chest was ordered (Figure 1), which revealed an apical left lower lobe mass extending into the left hilum encasing part of the ascending aorta. Enlarged mediastinal subcentimeter paratracheal and superior mediastinal lymph nodes also were identified and the pattern raised the concern for lymphangitic carcinomatosis. Dr. Fine, what do you make of the CT findings?
► Alan Fine, MD, Section of Pulmonary and Critical Care, VABHS and Professor of Medicine, Boston University School of Medicine: This mass had irregular edges with septal thickening, which may be why there was a concern for lymphangitic spread. There were no clear tissue planes to see if this process was invading the mediastinum. The mass was irregular, a single lesion, and proximal, making it consistent with a lung cancer. In fact, with his history of smoking, asbestos exposure, the numbers 1 to 10 diagnoses were lung cancer. The lack of demarcation of tissue planes supports this. There are some infections, classically actinomycosis, that do cross and invade anatomical barriers.1 But this looked like a primary lung cancer.
► Dr. Apte: The patient was referred to a pulmonologist where an additional history of night sweats and weight loss were noted. Dr. Fine, we have a patient with a newly identified lung mass, and while we have reason to suspect malignancy as you have already noted, there are many other etiologies to consider, including infections (histoplasmosis, cryptococcosis, bacterial abscess), inflammatory processes (sarcoidosis, rheumatoid nodule) and vasculitis (granulomatosis with polyangiitis). What should be the next step taken to make a diagnosis?
►Dr. Fine: For cancer specifically, we would like to both stage and make a diagnosis with one procedure. That’s part of the utility of a positron emission tomography (PET) scan: We can see lymph node involvement and stage the cancer. We must consider the patient’s comorbidities and the location of the lesion (ie, is it amenable to needle biopsy?). In this case, there are enlarged mediastinal lymph nodes, so one could perform a bronchoscopy with endobronchial ultrasound, which is a relatively noninvasive way to sample the lymph nodes to ideally stage and make a diagnosis as safely as possible. If we are considering infection, needle aspiration is not as sensitive.2
► Dr. Apte: The patient underwent a PET CT, which redemonstrated the lung mass with a loss of aortic fat plane suspicious for aortic involvement as well as lymph nodes in levels 7 and 8 that were concerning for malignancy. Subsequent bronchoscopy with biopsy and endobronchial ultrasound did not show evidence of malignancy; washing and brushing from the mass and lymph node specimens did not identify malignant cells. Benign respiratory mucosa with mild chronic inflammation was noted. Dr. Fine, given the nonspecific findings on the PET scan, negative findings on our bronchoscopy, and a negative biopsy, should we be satisfied that we have ruled out cancer?
► Dr. Fine: No, bronchoscopy has its limitations. It’s highly sensitive to the diagnosis of malignancy if you can see an endobronchial lesion, but we did not see one here. You can only go so far with the scope, and it’s not uncommon for us not to be able to make the diagnosis with bronchoscopy. Malignancy is still the most likely diagnosis, and we need to work this up further. I would perform another biopsy.
►Dr. Apte: Four weeks later, the patient presented with continued shortness of breath, fatigue, and fever. A repeat chest CT showed an opacity suggestive of pneumonia. Given the continued concern for cancer a CT-guided needle biopsy was performed and was once again negative for malignancy. The decision was made to pursue a video-assisted thorascopic surgery (VATS). Following the VATS, the patient developed rigors, fever, and tachycardia with new atrial fibrillation. While being evaluated hypercalcemia was identified, with further workup revealing a low parathyroid hormone (PTH) and low PTH-related peptide. Dr. Fine, the presence of hypercalcemia and a new arrythmia raised the possibility of sarcoidosis. Could this be sarcoidosis?
►Dr. Fine: Sarcoidosis is one of the great masqueraders in medicine. There is a type of sarcoidosis called nodular sarcoidosis where you see masslike distribution in the lung, but generally there are multiple masses and so this presentation would be atypical.3 There is also a phenomenon called sarcoidal reactions usually in the presence of cancer. Again, one tends to see multiple tiny lesions in the lung. It is certainly on the differential, but I would consider it to be less likely than cancer. It is also relatively common to develop atrial fibrillation after manipulation from a lung surgery.4 The other possibility I am concerned about is whether the mass is invading the mediastinum and involving the pericardium.
►Dr. Apte: Results from the VATS biopsy once again returned negative for malignancy and instead showed signs of focal micro-abscesses, atypical pneumocytes, and prominent neutrophils. A diagnosis of acute fibrinous organizing pneumonia (AFOP) was offered. Dr. Fine, what is AFOP?
►Dr. Fine: This is the first case of AFOP I had seen and probably the first case many in our department have seen. This is a relatively new entity with limited reported cases in the literature and is a pathological diagnosis originally recorded in autopsies from patients at the National Institutes of Health.5,6 Given the complexity of the lesion, the diagnosis is difficult to make. Most commonly, AFOP is associated with other systemic entities, most commonly hematologic malignancies like lymphomas and leukemias. It has also been associated with vasculitis and certain drugs. The mechanism is poorly understood, and although pneumonia is a part of the term, this just implies there is inflammation of the lung (ie, pneumonitis).
► Dr. Apte: Given the association of AFOP with underlying hematologic malignancies, an emphasis was placed on another finding: the patient’s increasing WBC count. The total WBC count had been 20 k/cm3 at the time of his lung mass discovery but had increased to > 40 k/cm3 with a differential of neutrophils > 80%. Flow cytometry was negative, and his peripheral smear was read as normal. Dr. Gilbert, what might explain this patient’s leukocytosis?
►Gary Gilbert, MD, Section of Hematology and Oncology, VABHS and Associate Professor of Medicine, Harvard Medical School (HMS): This patient had an elevated WBC for 4 months. Initially, the cause was likely lithium as this is known to cause a leukocytosis.7 More recently, the total WBC had increased and there were a couple of other abnormalities: A consistently elevated absolute monocyte count and a markedly elevated mature neutrophil count. These findings are consistent with a leukemoid reaction (ie, a WBC count > 50,000/µL from causes other than leukemia). The question becomes what is this a leukemoid reaction in response to? Once we have excluded a lung malignancy (a well-known common cause of a leukemoid reaction) we must consider a clonal myeloproliferative disorder. This is particularly true because many things that cause a leukemoid reaction (eg, lobar pneumonia) do not cause a persistently elevated neutrophil count. That this patient does have a persistently elevated neutrophil count suggests something abnormal about the neutrophils themselves.
► Dr. Apte: A bone marrow biopsy was performed. Dr. Gilbert, can you comment on this patient’s bone marrow biopsy and whether a myeloproliferative disorder may have played a role in the marked leukocytosis?
► Dr. Gilbert: The bone marrow biopsy was hyperplastic with myeloid predominance and normal maturation in all lineages. A deep sequencing analysis demonstrated the absence of chromosomal abnormalities or genetic mutations that are associated with myeloproliferative disorders. This excludes the possibility of a myeloproliferative disorder.
► Dr. Apte: The patient was started on 60 mg of prednisone daily, which led to marked improvement in his symptoms. He was discharged in stable condition but presented again with abdominal pain. A complete blood count once again showed increased WBC and new thrombocytosis. A CT angiogram (CTA) showed the prior lung mass with new signs of central necrosis. In the abdomen, new splenic and renal infarct were identified, along with signs of multiple arterial thrombi in the abdomen and internal and external iliac vessel wall thickening. These findings were read as concerning for a medium vessel vasculitis. Dr. Kaur, what are some of the imaging findings you would expect to see in vasculitis, and what about this patient’s CT is consistent with a medium vessel vasculitis?
► Maneet Kaur, MD, Section of Rheumatology, VABHS: Vasculitis is inflammation of the vessel wall that can lead to vascular injury and activation of the coagulation cascade. Sometimes these findings can be seen on imaging with evidence of stenosis, microaneurysms, and thrombosis distal to the stenosis. The nomenclature of vasculitis is not simple and has been revised many times. Medium-vessel vasculitis does not just affect the medium vessels (eg, visceral arteries) but can overlap with distal large vessels and smaller cutaneous vessels.
The first thing that comes to mind in this case is polyarteritis nodosa (PAN), an immune complex-mediated medium vessel disease that can involve large and small vessels in muscle, nerve, and skin. It can also present with masses.
►Dr. Apte: To address the arterial thrombi seen on CTA, arterial-brachial indices were obtained and showed bilateral occlusive disease in his distal extremities; findings that could be explained by vasculitis. His VATS biopsy pathology was reviewed for signs of vasculitis. Dr. Huang, can you review these slides for us please?
►Qin Huang, MD, Department of Pathology and Laboratory Medicine, VABHS and Assistant Professor of Pathology, HMS: This patient had a history of smoking, and there are many black pigment-laden macrophages present in the lung tissue. There were areas of hemorrhage and fibrin deposition and an overall picture of organizing pneumonia. At a lower power, you can see neutrophils everywhere, some in the form of micro-abscesses. The arterial walls did not show signs of vasculitis (Figure 2). Based on the clinical information and radiology findings, we suspected an acute infection-related pneumonia or a primary lung malignancy causing obstruction pneumonia. We suggested a rebiopsy of the lung mass to rule out a primary lung malignancy.
► Dr. Apte: Given his CT findings, a serologic rheumatologic workup including antineutrophil cytoplasmic antibody, antinuclear antibody, and rheumatoid factors were sent and returned negative. The location of arterial wall inflammation on imaging made it unamenable for biopsy. The patient began to experience bilateral temporal pain, which raised the concern for a large vessel vasculitis, specifically giant cell arteritis. Bilateral temporal artery biopsies were obtained and were not suggestive of vasculitis. Dr. Kaur, we still do not have any serologic or biopsy confirmation to support a diagnosis of vasculitis. Can we still call this a vasculitis?
►Dr. Kaur: Few things can cause the picture that was seen radiographically. A few noninflammatory causes like fibromuscular dysplasia can cause both large and small vessel stenosis, but the elevations in erythrocyte sedimentation rate and C-reactive protein along with response to steroids makes these diagnoses unlikely. Sometimes we must make a clinical diagnosis for vasculitis based on the clinical picture, and I would feel comfortable treating this patient for vasculitis.
With that said, I remain concerned that this patient also has a malignancy. His WBC increased to > 70 k/cm3 and his calcium to > 13 mg/dL. These findings are hard to explain by vasculitis alone. There are cancer-associated vasculitis, and I suspect this is the explanation here.8 His temporal pain was pointing to large vessel involvement, so he could have an undifferentiated vasculitis.
► Dr. Apte: A decision was made to empirically treat with tocilizumab, an IL-6 receptor antagonist, for an undifferentiated autoimmune disease, in addition to tapering steroids. The patient underwent a second VATS, which again revealed AFOP but no signs of malignancy. Unfortunately, he developed multiple complications over the subsequent weeks and passed away. An autopsy was requested by family members and pathology from his lung mass was reviewed. (Figure 3). Dr. Huang, can you review these slides for us?
► Dr. Huang: The left lung mass at autopsy shows nests, poorly formed clusters, and individuals of malignant neoplastic nonkeratinizing squamous cells embedded in a desmoplastic stroma in the mass center, consistent with poorly differentiated squamous cell carcinoma, and a circumscribed area of residual subacute organizing pneumonia with abscess, granulomatous changes, and early fibrosis at the periphery of this mass.
►Dr. Apte: Based on autopsy findings, the final diagnosis was poorly differentiated squamous cell carcinoma associated with subacute organizing pneumonia and medium vessel vasculitis, which presented with a severe leukocytosis ultimately thought to be a leukemoid reaction from his lung cancer.
1. Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014;7:183-197. Published 2014 Jul 5. doi:10.2147/IDR.S39601
2. de Bazelaire C, Coffin A, Cohen-Zarade S, et al. CT-guided biopsies in lung infections in patients with haematological malignancies. Diagn Interv Imaging. 2013;94(2):202-215. doi:10.1016/j.diii.2012.12.008
3. Sweidan AJ, Singh NK, Stein A, Tanios M. Nodular sarcoidosis masquerading as cancer. Clin Med Insights Circ Respir Pulm Med. 2017;11:1179548417703123. Published 2017 Apr 12. doi:10.1177/1179548417703123
4. Bagheri R, Yousefi Y, Rezai R, Azemonfar V, Keshtan FG. Atrial fibrillation after lung surgery: incidence, underlying factors, and predictors. Kardiochir Torakochirurgia Pol. 2019;16(2):53-56. doi:10.5114/kitp.2019.86355
5. Lu J, Yin Q, Zha Y, et al. Acute fibrinous and organizing pneumonia: two case reports and literature review. BMC Pulm Med. 2019;19(1):141. Published 2019 Aug 5. doi:10.1186/s12890-019-0861-3
6. Beasley MB, Franks TJ, Galvin JR, Gochuico B, Travis WD. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med. 2002;126(9):1064-1070. doi:10.5858/2002-126-1064-AFAOP
7. Murphy DL, Goodwin FK, Bunney WE Jr. Leukocytosis during lithium treatment. Am J Psychiatry. 1971;127(11):1559-1561. doi:10.1176/ajp.127.11.1559
8. Fain O, Hamidou M, Cacoub P, et al. Vasculitides associated with malignancies: analysis of sixty patients. Arthritis Rheum. 2007;57(8):1473-1480. doi:10.1002/art.23085
1. Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014;7:183-197. Published 2014 Jul 5. doi:10.2147/IDR.S39601
2. de Bazelaire C, Coffin A, Cohen-Zarade S, et al. CT-guided biopsies in lung infections in patients with haematological malignancies. Diagn Interv Imaging. 2013;94(2):202-215. doi:10.1016/j.diii.2012.12.008
3. Sweidan AJ, Singh NK, Stein A, Tanios M. Nodular sarcoidosis masquerading as cancer. Clin Med Insights Circ Respir Pulm Med. 2017;11:1179548417703123. Published 2017 Apr 12. doi:10.1177/1179548417703123
4. Bagheri R, Yousefi Y, Rezai R, Azemonfar V, Keshtan FG. Atrial fibrillation after lung surgery: incidence, underlying factors, and predictors. Kardiochir Torakochirurgia Pol. 2019;16(2):53-56. doi:10.5114/kitp.2019.86355
5. Lu J, Yin Q, Zha Y, et al. Acute fibrinous and organizing pneumonia: two case reports and literature review. BMC Pulm Med. 2019;19(1):141. Published 2019 Aug 5. doi:10.1186/s12890-019-0861-3
6. Beasley MB, Franks TJ, Galvin JR, Gochuico B, Travis WD. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med. 2002;126(9):1064-1070. doi:10.5858/2002-126-1064-AFAOP
7. Murphy DL, Goodwin FK, Bunney WE Jr. Leukocytosis during lithium treatment. Am J Psychiatry. 1971;127(11):1559-1561. doi:10.1176/ajp.127.11.1559
8. Fain O, Hamidou M, Cacoub P, et al. Vasculitides associated with malignancies: analysis of sixty patients. Arthritis Rheum. 2007;57(8):1473-1480. doi:10.1002/art.23085
Stopping Empagliflozin Unmasks Heart Failure
SGLT2 inhibitors have been shown to have a role in the management of heart failure in patients with type 2 diabetes mellitus, but there is a risk of exacerbation when discontinued.
About 40% of patients with heart failure (HF) also have type 2 diabetes mellitus (T2DM).1 Certain sodium-glucose cotransporter-2 (SGLT2) inhibitors have benefited patients with HF.2 We report a case of a patient with T2DM who had signs and symptoms of hypervolemia after discontinuing the SGLT2 inhibitor empagliflozin. The patient was found to have previously undiagnosed HF.
Case Presentation
A 58-year-old male presented for care at Malcolm Randall Veterans Affairs Medical Center in Gainseville, Florida, diabetes clinic. The patient was diagnosed with T2DM at age 32 years. At 36 years, he was started on subcutaneous insulin injections, and was switched to insulin pump therapy in his early 40s. At the time of evaluation, the T2DM was managed using an insulin pump, metformin, and acarbose. He had been prescribed empagliflozin 10 mg several months before presentation, but the medication ran out about 1 month prior to evaluation, and additional refills were unavailable.
The patient reported a 1-month history of worsening exertional shortness of breath, decreased exercise tolerance, and lower extremity swelling. Vitals signs, including respiratory rate and oxygen saturation were within normal limits. Bibasilar crackles and bilateral 2+ pitting pedal edema were noted. The remaining examination was unrevealing. His most recent glycated hemoglobin A1c level from 1 month prior to the presentation was 6.4%.
Given the patient’s shortness of breath and evidence of fluid overload on examination, brain natriuretic peptide was obtained and was significantly elevated at 5,895 pg/mL. A transthoracic echocardiogram revealed left ventricular ejection fraction < 20%. The patient was started on furosemide 40 mg, pending receipt of empagliflozin. A cardiology evaluation also was recommended.
Cardiac catheterization identified significant obstructions to the left anterior descending and left circumflex arteries. The patient underwent successful percutaneous coronary intervention to these areas. Following initiation of medications and coronary revascularization, the patient reported significant symptom improvement. At the follow-up evaluation 8 weeks later, he was symptom free, and his physical examination was consistent with euvolemia.
Discussion
T2DM has been associated with adverse cardiovascular outcomes, including atherosclerotic heart disease and HF. There are several theories about the relationship between T2DM and HF, though the exact pathophysiology of this relationship is unknown.3,4 One theory suggests diabetic cardiomyopathy as the cause. In patients with diabetic cardiomyopathy, there is early development of diastolic dysfunction, which eventually progresses to ventricular dysfunction. There is continued stimulation of the renin-angiotensin-aldosterone system that leads to death of cardiomyocytes, fibrosis, and remodeling, which worsens pump failure.5
SGLT2 inhibitors decrease hyperglycemia and hyperinsulinemia, potentially reducing HF risk. SGLT2 inhibitors decrease blood glucose levels by inhibiting SGLT2 in the proximal tubule, leading to a decrease of glucose reabsorption and an increase in excretion.6,7 The EMPA-REG OUTCOME trial looked at cardiovascular outcomes in patients with T2DM at high risk for adverse cardiac events. There was a significant risk reduction in deaths and hospitalizations for HF in patients treated with empagliflozin.8
The EMPRISE study specifically examined empagliflozin and its effects on hospitalization for HF.2 When compared with patients treated with sitagliptin, there was a statistically significant decrease in hospitalization for HF in patients with T2DM, both with and without preexisting cardiovascular disease.
This case highlights the relationship between T2DM and HF. We also show how the use of empagliflozin may have helped manage the patient’s undiagnosed HF and how its discontinuation luckily unmasked it. Routine evaluation for HF in patients with T2DM is not done, but likely there are patients who would benefit, especially given the strong, albeit less known, association between these 2 conditions.
Further studies are needed to determine the type of patients who would benefit most from HF screening. For now, the best practice is to obtain a complete medical history that includes current and recently discontinued medications as well a thorough physical examination for signs of fluid overload and cardiovascular compromise. Patients who may have signs concerning for HF can have appropriate testing and intervention.
Conclusions
SGLT2 inhibitors have been shown to have a role in the management of HF in patients with T2DM. There is a risk of exacerbation or unmasking of HF when discontinuing SGLT2 inhibitors. To our knowledge, this is the first paper describing the discovery of HF following interruption of SGLT2 inhibitor treatment. The clinician and patient should monitor for signs and symptoms of fluid overload when stopping therapy. Further research into the benefits of a more comprehensive evaluation is needed.
1. Thomas MC. Type 2 diabetes and heart failure: challenges and solutions. Curr Cardiol Rev. 2016;12(3):249-255. doi:10.2174/1573403X12666160606120254
2. Patorno E, Pawar A, Franklin J, et al. Empagliflozin and the risk of heart failure hospitalization in routine clinical care: a first analysis from the EMPRISE study. Circulation. 2019;139(25):2822-2830. doi:10.1161/CIRCULATIONAHA.118.039177
3. Packer M. Heart failure: the most important, preventable, and treatable cardiovascular complication of type 2 diabetes. Diabetes Care. 2018;41(1):11-13. doi:10.2337/dci17-0052
4. Thrainsdottir I, Aspelund T, Thorheirsson G, et al. The association between glucose abnormalities and heart failure in the population-based Reykjavík study. Diabetes Care. 2005;28(3):612-616. doi:10.2337/diacare.28.3.612
5. Bell D, Goncalves E. Heart failure in the patient with diabetes: epidemiology, aetiology, prognosis, therapy and the effect of glucose-lowering medications. Diabetes Obes Metab. 2019;21(6):1277-1290. doi:10.1111/dom.13652
6. Nair S, Wilding JPH. Sodium glucose cotransporter 2 Inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab. 2010;95(1):34-42. doi:10.1210/jc.2009-0473
7. Ali A, Bain S, Hicks D, et al; Improving Diabetes Steering Committee. SGLT2 inhibitors: cardiovascular benefits beyond HbA1c- translating evidence into practice. Diabetes Ther. 2019;10(5):1595-1622. doi:10.1007/s13300-019-0657-8
8. Zinman B, Wanner C, Lachin J, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720
SGLT2 inhibitors have been shown to have a role in the management of heart failure in patients with type 2 diabetes mellitus, but there is a risk of exacerbation when discontinued.
SGLT2 inhibitors have been shown to have a role in the management of heart failure in patients with type 2 diabetes mellitus, but there is a risk of exacerbation when discontinued.
About 40% of patients with heart failure (HF) also have type 2 diabetes mellitus (T2DM).1 Certain sodium-glucose cotransporter-2 (SGLT2) inhibitors have benefited patients with HF.2 We report a case of a patient with T2DM who had signs and symptoms of hypervolemia after discontinuing the SGLT2 inhibitor empagliflozin. The patient was found to have previously undiagnosed HF.
Case Presentation
A 58-year-old male presented for care at Malcolm Randall Veterans Affairs Medical Center in Gainseville, Florida, diabetes clinic. The patient was diagnosed with T2DM at age 32 years. At 36 years, he was started on subcutaneous insulin injections, and was switched to insulin pump therapy in his early 40s. At the time of evaluation, the T2DM was managed using an insulin pump, metformin, and acarbose. He had been prescribed empagliflozin 10 mg several months before presentation, but the medication ran out about 1 month prior to evaluation, and additional refills were unavailable.
The patient reported a 1-month history of worsening exertional shortness of breath, decreased exercise tolerance, and lower extremity swelling. Vitals signs, including respiratory rate and oxygen saturation were within normal limits. Bibasilar crackles and bilateral 2+ pitting pedal edema were noted. The remaining examination was unrevealing. His most recent glycated hemoglobin A1c level from 1 month prior to the presentation was 6.4%.
Given the patient’s shortness of breath and evidence of fluid overload on examination, brain natriuretic peptide was obtained and was significantly elevated at 5,895 pg/mL. A transthoracic echocardiogram revealed left ventricular ejection fraction < 20%. The patient was started on furosemide 40 mg, pending receipt of empagliflozin. A cardiology evaluation also was recommended.
Cardiac catheterization identified significant obstructions to the left anterior descending and left circumflex arteries. The patient underwent successful percutaneous coronary intervention to these areas. Following initiation of medications and coronary revascularization, the patient reported significant symptom improvement. At the follow-up evaluation 8 weeks later, he was symptom free, and his physical examination was consistent with euvolemia.
Discussion
T2DM has been associated with adverse cardiovascular outcomes, including atherosclerotic heart disease and HF. There are several theories about the relationship between T2DM and HF, though the exact pathophysiology of this relationship is unknown.3,4 One theory suggests diabetic cardiomyopathy as the cause. In patients with diabetic cardiomyopathy, there is early development of diastolic dysfunction, which eventually progresses to ventricular dysfunction. There is continued stimulation of the renin-angiotensin-aldosterone system that leads to death of cardiomyocytes, fibrosis, and remodeling, which worsens pump failure.5
SGLT2 inhibitors decrease hyperglycemia and hyperinsulinemia, potentially reducing HF risk. SGLT2 inhibitors decrease blood glucose levels by inhibiting SGLT2 in the proximal tubule, leading to a decrease of glucose reabsorption and an increase in excretion.6,7 The EMPA-REG OUTCOME trial looked at cardiovascular outcomes in patients with T2DM at high risk for adverse cardiac events. There was a significant risk reduction in deaths and hospitalizations for HF in patients treated with empagliflozin.8
The EMPRISE study specifically examined empagliflozin and its effects on hospitalization for HF.2 When compared with patients treated with sitagliptin, there was a statistically significant decrease in hospitalization for HF in patients with T2DM, both with and without preexisting cardiovascular disease.
This case highlights the relationship between T2DM and HF. We also show how the use of empagliflozin may have helped manage the patient’s undiagnosed HF and how its discontinuation luckily unmasked it. Routine evaluation for HF in patients with T2DM is not done, but likely there are patients who would benefit, especially given the strong, albeit less known, association between these 2 conditions.
Further studies are needed to determine the type of patients who would benefit most from HF screening. For now, the best practice is to obtain a complete medical history that includes current and recently discontinued medications as well a thorough physical examination for signs of fluid overload and cardiovascular compromise. Patients who may have signs concerning for HF can have appropriate testing and intervention.
Conclusions
SGLT2 inhibitors have been shown to have a role in the management of HF in patients with T2DM. There is a risk of exacerbation or unmasking of HF when discontinuing SGLT2 inhibitors. To our knowledge, this is the first paper describing the discovery of HF following interruption of SGLT2 inhibitor treatment. The clinician and patient should monitor for signs and symptoms of fluid overload when stopping therapy. Further research into the benefits of a more comprehensive evaluation is needed.
About 40% of patients with heart failure (HF) also have type 2 diabetes mellitus (T2DM).1 Certain sodium-glucose cotransporter-2 (SGLT2) inhibitors have benefited patients with HF.2 We report a case of a patient with T2DM who had signs and symptoms of hypervolemia after discontinuing the SGLT2 inhibitor empagliflozin. The patient was found to have previously undiagnosed HF.
Case Presentation
A 58-year-old male presented for care at Malcolm Randall Veterans Affairs Medical Center in Gainseville, Florida, diabetes clinic. The patient was diagnosed with T2DM at age 32 years. At 36 years, he was started on subcutaneous insulin injections, and was switched to insulin pump therapy in his early 40s. At the time of evaluation, the T2DM was managed using an insulin pump, metformin, and acarbose. He had been prescribed empagliflozin 10 mg several months before presentation, but the medication ran out about 1 month prior to evaluation, and additional refills were unavailable.
The patient reported a 1-month history of worsening exertional shortness of breath, decreased exercise tolerance, and lower extremity swelling. Vitals signs, including respiratory rate and oxygen saturation were within normal limits. Bibasilar crackles and bilateral 2+ pitting pedal edema were noted. The remaining examination was unrevealing. His most recent glycated hemoglobin A1c level from 1 month prior to the presentation was 6.4%.
Given the patient’s shortness of breath and evidence of fluid overload on examination, brain natriuretic peptide was obtained and was significantly elevated at 5,895 pg/mL. A transthoracic echocardiogram revealed left ventricular ejection fraction < 20%. The patient was started on furosemide 40 mg, pending receipt of empagliflozin. A cardiology evaluation also was recommended.
Cardiac catheterization identified significant obstructions to the left anterior descending and left circumflex arteries. The patient underwent successful percutaneous coronary intervention to these areas. Following initiation of medications and coronary revascularization, the patient reported significant symptom improvement. At the follow-up evaluation 8 weeks later, he was symptom free, and his physical examination was consistent with euvolemia.
Discussion
T2DM has been associated with adverse cardiovascular outcomes, including atherosclerotic heart disease and HF. There are several theories about the relationship between T2DM and HF, though the exact pathophysiology of this relationship is unknown.3,4 One theory suggests diabetic cardiomyopathy as the cause. In patients with diabetic cardiomyopathy, there is early development of diastolic dysfunction, which eventually progresses to ventricular dysfunction. There is continued stimulation of the renin-angiotensin-aldosterone system that leads to death of cardiomyocytes, fibrosis, and remodeling, which worsens pump failure.5
SGLT2 inhibitors decrease hyperglycemia and hyperinsulinemia, potentially reducing HF risk. SGLT2 inhibitors decrease blood glucose levels by inhibiting SGLT2 in the proximal tubule, leading to a decrease of glucose reabsorption and an increase in excretion.6,7 The EMPA-REG OUTCOME trial looked at cardiovascular outcomes in patients with T2DM at high risk for adverse cardiac events. There was a significant risk reduction in deaths and hospitalizations for HF in patients treated with empagliflozin.8
The EMPRISE study specifically examined empagliflozin and its effects on hospitalization for HF.2 When compared with patients treated with sitagliptin, there was a statistically significant decrease in hospitalization for HF in patients with T2DM, both with and without preexisting cardiovascular disease.
This case highlights the relationship between T2DM and HF. We also show how the use of empagliflozin may have helped manage the patient’s undiagnosed HF and how its discontinuation luckily unmasked it. Routine evaluation for HF in patients with T2DM is not done, but likely there are patients who would benefit, especially given the strong, albeit less known, association between these 2 conditions.
Further studies are needed to determine the type of patients who would benefit most from HF screening. For now, the best practice is to obtain a complete medical history that includes current and recently discontinued medications as well a thorough physical examination for signs of fluid overload and cardiovascular compromise. Patients who may have signs concerning for HF can have appropriate testing and intervention.
Conclusions
SGLT2 inhibitors have been shown to have a role in the management of HF in patients with T2DM. There is a risk of exacerbation or unmasking of HF when discontinuing SGLT2 inhibitors. To our knowledge, this is the first paper describing the discovery of HF following interruption of SGLT2 inhibitor treatment. The clinician and patient should monitor for signs and symptoms of fluid overload when stopping therapy. Further research into the benefits of a more comprehensive evaluation is needed.
1. Thomas MC. Type 2 diabetes and heart failure: challenges and solutions. Curr Cardiol Rev. 2016;12(3):249-255. doi:10.2174/1573403X12666160606120254
2. Patorno E, Pawar A, Franklin J, et al. Empagliflozin and the risk of heart failure hospitalization in routine clinical care: a first analysis from the EMPRISE study. Circulation. 2019;139(25):2822-2830. doi:10.1161/CIRCULATIONAHA.118.039177
3. Packer M. Heart failure: the most important, preventable, and treatable cardiovascular complication of type 2 diabetes. Diabetes Care. 2018;41(1):11-13. doi:10.2337/dci17-0052
4. Thrainsdottir I, Aspelund T, Thorheirsson G, et al. The association between glucose abnormalities and heart failure in the population-based Reykjavík study. Diabetes Care. 2005;28(3):612-616. doi:10.2337/diacare.28.3.612
5. Bell D, Goncalves E. Heart failure in the patient with diabetes: epidemiology, aetiology, prognosis, therapy and the effect of glucose-lowering medications. Diabetes Obes Metab. 2019;21(6):1277-1290. doi:10.1111/dom.13652
6. Nair S, Wilding JPH. Sodium glucose cotransporter 2 Inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab. 2010;95(1):34-42. doi:10.1210/jc.2009-0473
7. Ali A, Bain S, Hicks D, et al; Improving Diabetes Steering Committee. SGLT2 inhibitors: cardiovascular benefits beyond HbA1c- translating evidence into practice. Diabetes Ther. 2019;10(5):1595-1622. doi:10.1007/s13300-019-0657-8
8. Zinman B, Wanner C, Lachin J, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720
1. Thomas MC. Type 2 diabetes and heart failure: challenges and solutions. Curr Cardiol Rev. 2016;12(3):249-255. doi:10.2174/1573403X12666160606120254
2. Patorno E, Pawar A, Franklin J, et al. Empagliflozin and the risk of heart failure hospitalization in routine clinical care: a first analysis from the EMPRISE study. Circulation. 2019;139(25):2822-2830. doi:10.1161/CIRCULATIONAHA.118.039177
3. Packer M. Heart failure: the most important, preventable, and treatable cardiovascular complication of type 2 diabetes. Diabetes Care. 2018;41(1):11-13. doi:10.2337/dci17-0052
4. Thrainsdottir I, Aspelund T, Thorheirsson G, et al. The association between glucose abnormalities and heart failure in the population-based Reykjavík study. Diabetes Care. 2005;28(3):612-616. doi:10.2337/diacare.28.3.612
5. Bell D, Goncalves E. Heart failure in the patient with diabetes: epidemiology, aetiology, prognosis, therapy and the effect of glucose-lowering medications. Diabetes Obes Metab. 2019;21(6):1277-1290. doi:10.1111/dom.13652
6. Nair S, Wilding JPH. Sodium glucose cotransporter 2 Inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab. 2010;95(1):34-42. doi:10.1210/jc.2009-0473
7. Ali A, Bain S, Hicks D, et al; Improving Diabetes Steering Committee. SGLT2 inhibitors: cardiovascular benefits beyond HbA1c- translating evidence into practice. Diabetes Ther. 2019;10(5):1595-1622. doi:10.1007/s13300-019-0657-8
8. Zinman B, Wanner C, Lachin J, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720
Cortical surface changes tied to risk for movement disorders in schizophrenia
Schizophrenia patients with parkinsonism show distinctive patterns of cortical surface markers, compared with schizophrenia patients without parkinsonism and healthy controls, results of a multimodal magnetic resonance imaging study suggest.
Sensorimotor abnormalities are common in schizophrenia patients, however, “the neurobiological mechanisms underlying parkinsonism in [schizophrenia], which in treated samples represents the unity of interplay between spontaneous and antipsychotic drug-exacerbated movement disorder, are poorly understood,” wrote Robert Christian Wolf, MD, of Heidelberg (Germany) University, and colleagues.
In a study published in Schizophrenia Research (2021 May;231:54-60), the investigators examined brain imaging findings from 20 healthy controls, 38 schizophrenia patients with parkinsonism (SZ-P), and 35 schizophrenia patients without parkinsonism (SZ-nonP). Dr. Wolf and colleagues examined three cortical surface markers: cortical thickness, complexity of cortical folding, and sulcus depth.
Compared with SZ-nonP patients, the SZ-P patients showed significantly increased complexity of cortical folding in the left supplementary motor cortex (SMC) and significantly decreased left postcentral sulcus (PCS) depth. In addition, left SMC activity was higher in both SZ-P and SZ-nonP patient groups, compared with controls.
In a regression analysis, the researchers examined relationships between parkinsonism severity and brain structure. They found that parkinsonism severity was negatively associated with left middle frontal complexity of cortical folding and left anterior cingulate cortex cortical thickness.
“Overall, the data support the notion that cortical features of distinct neurodevelopmental origin, particularly cortical folding indices such as [complexity of cortical folding] and sulcus depth, contribute to the pathogenesis of parkinsonism in SZ,” the researchers wrote.
The study findings were limited by several factors, including the cross-sectional design, the potential limitations of the Simpson-Angus Scale in characterizing parkinsonism, the inability to record lifetime antibiotics exposure in the patient population, and the inability to identify changes in brain stem nuclei, the researchers noted. However, the results were strengthened by the well-matched study groups and use of multimodal MRI, they said.
Consequently, “,” and suggest a link between abnormal neurodevelopmental processes and an increased risk for movement disorders in schizophrenia, they concluded.
The study was funded by the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Wolf and colleagues disclosed no conflicts.
Schizophrenia patients with parkinsonism show distinctive patterns of cortical surface markers, compared with schizophrenia patients without parkinsonism and healthy controls, results of a multimodal magnetic resonance imaging study suggest.
Sensorimotor abnormalities are common in schizophrenia patients, however, “the neurobiological mechanisms underlying parkinsonism in [schizophrenia], which in treated samples represents the unity of interplay between spontaneous and antipsychotic drug-exacerbated movement disorder, are poorly understood,” wrote Robert Christian Wolf, MD, of Heidelberg (Germany) University, and colleagues.
In a study published in Schizophrenia Research (2021 May;231:54-60), the investigators examined brain imaging findings from 20 healthy controls, 38 schizophrenia patients with parkinsonism (SZ-P), and 35 schizophrenia patients without parkinsonism (SZ-nonP). Dr. Wolf and colleagues examined three cortical surface markers: cortical thickness, complexity of cortical folding, and sulcus depth.
Compared with SZ-nonP patients, the SZ-P patients showed significantly increased complexity of cortical folding in the left supplementary motor cortex (SMC) and significantly decreased left postcentral sulcus (PCS) depth. In addition, left SMC activity was higher in both SZ-P and SZ-nonP patient groups, compared with controls.
In a regression analysis, the researchers examined relationships between parkinsonism severity and brain structure. They found that parkinsonism severity was negatively associated with left middle frontal complexity of cortical folding and left anterior cingulate cortex cortical thickness.
“Overall, the data support the notion that cortical features of distinct neurodevelopmental origin, particularly cortical folding indices such as [complexity of cortical folding] and sulcus depth, contribute to the pathogenesis of parkinsonism in SZ,” the researchers wrote.
The study findings were limited by several factors, including the cross-sectional design, the potential limitations of the Simpson-Angus Scale in characterizing parkinsonism, the inability to record lifetime antibiotics exposure in the patient population, and the inability to identify changes in brain stem nuclei, the researchers noted. However, the results were strengthened by the well-matched study groups and use of multimodal MRI, they said.
Consequently, “,” and suggest a link between abnormal neurodevelopmental processes and an increased risk for movement disorders in schizophrenia, they concluded.
The study was funded by the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Wolf and colleagues disclosed no conflicts.
Schizophrenia patients with parkinsonism show distinctive patterns of cortical surface markers, compared with schizophrenia patients without parkinsonism and healthy controls, results of a multimodal magnetic resonance imaging study suggest.
Sensorimotor abnormalities are common in schizophrenia patients, however, “the neurobiological mechanisms underlying parkinsonism in [schizophrenia], which in treated samples represents the unity of interplay between spontaneous and antipsychotic drug-exacerbated movement disorder, are poorly understood,” wrote Robert Christian Wolf, MD, of Heidelberg (Germany) University, and colleagues.
In a study published in Schizophrenia Research (2021 May;231:54-60), the investigators examined brain imaging findings from 20 healthy controls, 38 schizophrenia patients with parkinsonism (SZ-P), and 35 schizophrenia patients without parkinsonism (SZ-nonP). Dr. Wolf and colleagues examined three cortical surface markers: cortical thickness, complexity of cortical folding, and sulcus depth.
Compared with SZ-nonP patients, the SZ-P patients showed significantly increased complexity of cortical folding in the left supplementary motor cortex (SMC) and significantly decreased left postcentral sulcus (PCS) depth. In addition, left SMC activity was higher in both SZ-P and SZ-nonP patient groups, compared with controls.
In a regression analysis, the researchers examined relationships between parkinsonism severity and brain structure. They found that parkinsonism severity was negatively associated with left middle frontal complexity of cortical folding and left anterior cingulate cortex cortical thickness.
“Overall, the data support the notion that cortical features of distinct neurodevelopmental origin, particularly cortical folding indices such as [complexity of cortical folding] and sulcus depth, contribute to the pathogenesis of parkinsonism in SZ,” the researchers wrote.
The study findings were limited by several factors, including the cross-sectional design, the potential limitations of the Simpson-Angus Scale in characterizing parkinsonism, the inability to record lifetime antibiotics exposure in the patient population, and the inability to identify changes in brain stem nuclei, the researchers noted. However, the results were strengthened by the well-matched study groups and use of multimodal MRI, they said.
Consequently, “,” and suggest a link between abnormal neurodevelopmental processes and an increased risk for movement disorders in schizophrenia, they concluded.
The study was funded by the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Wolf and colleagues disclosed no conflicts.
FROM SCHIZOPHRENIA RESEARCH
Reflections on 10 years of hospitalist productivity
Successful programs will recruit lifelong learners
The workload of individual hospitalists has long been a hot-button issue. In a 2013 survey of hospitalists, 40% felt workloads were unsafe on a monthly basis, and 22% reported ordering unnecessary testing or procedures because of time pressure.1 In a 2014 analysis of over 20,000 admissions to an academic hospital medicine service, increasing workload led to increased length of stay and cost per case.2 Although these studies suggest a “sweet spot” for hospitalist workload, many groups face constant pressure to increase revenue.
Over the past decade there has been a significant change in how hospital medicine programs are financed. In the 2010 State of Hospital Medicine (SoHM), the median financial support per physician hospitalist in adult hospital medicine groups (HMGs) was $98,253. By the 2020 SoHM, the financial support was $198,750, an increase of $100,497 in just 10 years. When this is combined with the explosive growth in the number of hospitalists, there is one inescapable conclusion – hospital medicine is expensive.
Over this same 10 years, net collections per hospitalist grew from $194,440 in 2010 to $216,779 in 2020, an increase of $22,339. The increase was caused by higher collections per encounter, not more encounters. Additionally, median compensation for adult/internal medicine hospitalists increased over the same period from $215,000 to $307,336, an increase of $92,336, or 43%. That is an increase of 3.7% per year, more than twice the rate of inflation or wage growth in the general economy over the same period. About 75% of this increase was funded by hospital support. It is clear – health care systems continue to find value in investing in hospitalists and hospital medicine programs.
With mounting costs for hospitals, there is pressure for the hospitalist model of care to change or for yearly billable encounters per hospitalist full-time equivalent to increase. Yet, the productivity of hospitalists, as measured by median billable encounters per year has remained flat. The 2010 SoHM listed median number of billable encounters per year for an internal medicine hospitalist as 2,230. In 2020, the number is 2,246 – a trivial 0.7% increase per decade, what amounts to a rounding error. There has been wiggle up and down over the years, but I suspect these are not trends but noise.
So the question is why. I think it is partly because hospital medicine leaders together with the leaders of their health care systems seem to be reaching an equilibrium. Productivity will always remain an expectation. This expectation will vary based on local circumstances. But for many HMGs, the days when productivity is pushed as the primary objective seem to be disappearing. Most hospital leaders seem to now understand that high productivity can be detrimental to other program goals.
But if productivity is flat, do 40% of hospitalists still feel they are providing unsafe care on a monthly basis? Without another study we don’t know, but here are some reasons why I’m hopeful. First, the hospitalist workforce is more experienced than 10 years ago and may be more efficient. Second, hospital medicine groups are larger and are therefore enabled to schedule more flexibly or enact jeopardy systems to level out workload on busy days. And lastly, hospitalists who feel they are providing unsafe care find greener pastures. The 2010 SoHM reported adult hospital medicine programs had a median 14.3% turnover rate. The 2020 SoHM turnover was 10.9%. While this is up from 2018 (7.4%) and 2016 (6.9%), the general trend is down.
Additionally, we all need to consider the possibility that there will be a disruptive innovation that will allow greater productivity for individual hospitalists while maintaining value. It is apparent the EHR is not yet that breakthrough. We all need to keep our eyes open, stay flexible, and be prepared to meet evolving demands on our programs.
We will see constant demands on hospitalists. But I’m hopeful that going forward expectations will increasingly shift away from simply working harder and seeing more patients, toward goals related to improving performance. Training programs generally produce excellent clinicians, but they often do not equip physicians to be excellent hospitalists. Successful hospital medicine programs will recruit lifelong learners and career hospitalists who are flexible and willing to innovate and adapt. The best programs will have structures in place to help excellent clinicians mature into the role of excellent hospitalists, and leaders that create and foster an environment of excellence.
Discover more 2020 SoHM Report data at www.hospitalmedicine.org/sohm.
Dr. Frederickson is medical director, hospital medicine and palliative care, at CHI Health, Omaha, Neb., and assistant professor at Creighton University, Omaha.
References
1. Michtalik HJ et al. Impact of Attending Physician Workload on Patient Care: A Survey of Hospitalists. JAMA Intern Med. 2013;173(5):375-7. doi: 10.1001/jamainternmed.2013.1864.
2. Elliott DJ et al. Effect of Hospitalist Workload on the Quality and Efficiency of Care. JAMA Intern Med. 2014;174(5):786-93. doi: 10.1001/jamainternmed.2014.300.
Successful programs will recruit lifelong learners
Successful programs will recruit lifelong learners
The workload of individual hospitalists has long been a hot-button issue. In a 2013 survey of hospitalists, 40% felt workloads were unsafe on a monthly basis, and 22% reported ordering unnecessary testing or procedures because of time pressure.1 In a 2014 analysis of over 20,000 admissions to an academic hospital medicine service, increasing workload led to increased length of stay and cost per case.2 Although these studies suggest a “sweet spot” for hospitalist workload, many groups face constant pressure to increase revenue.
Over the past decade there has been a significant change in how hospital medicine programs are financed. In the 2010 State of Hospital Medicine (SoHM), the median financial support per physician hospitalist in adult hospital medicine groups (HMGs) was $98,253. By the 2020 SoHM, the financial support was $198,750, an increase of $100,497 in just 10 years. When this is combined with the explosive growth in the number of hospitalists, there is one inescapable conclusion – hospital medicine is expensive.
Over this same 10 years, net collections per hospitalist grew from $194,440 in 2010 to $216,779 in 2020, an increase of $22,339. The increase was caused by higher collections per encounter, not more encounters. Additionally, median compensation for adult/internal medicine hospitalists increased over the same period from $215,000 to $307,336, an increase of $92,336, or 43%. That is an increase of 3.7% per year, more than twice the rate of inflation or wage growth in the general economy over the same period. About 75% of this increase was funded by hospital support. It is clear – health care systems continue to find value in investing in hospitalists and hospital medicine programs.
With mounting costs for hospitals, there is pressure for the hospitalist model of care to change or for yearly billable encounters per hospitalist full-time equivalent to increase. Yet, the productivity of hospitalists, as measured by median billable encounters per year has remained flat. The 2010 SoHM listed median number of billable encounters per year for an internal medicine hospitalist as 2,230. In 2020, the number is 2,246 – a trivial 0.7% increase per decade, what amounts to a rounding error. There has been wiggle up and down over the years, but I suspect these are not trends but noise.
So the question is why. I think it is partly because hospital medicine leaders together with the leaders of their health care systems seem to be reaching an equilibrium. Productivity will always remain an expectation. This expectation will vary based on local circumstances. But for many HMGs, the days when productivity is pushed as the primary objective seem to be disappearing. Most hospital leaders seem to now understand that high productivity can be detrimental to other program goals.
But if productivity is flat, do 40% of hospitalists still feel they are providing unsafe care on a monthly basis? Without another study we don’t know, but here are some reasons why I’m hopeful. First, the hospitalist workforce is more experienced than 10 years ago and may be more efficient. Second, hospital medicine groups are larger and are therefore enabled to schedule more flexibly or enact jeopardy systems to level out workload on busy days. And lastly, hospitalists who feel they are providing unsafe care find greener pastures. The 2010 SoHM reported adult hospital medicine programs had a median 14.3% turnover rate. The 2020 SoHM turnover was 10.9%. While this is up from 2018 (7.4%) and 2016 (6.9%), the general trend is down.
Additionally, we all need to consider the possibility that there will be a disruptive innovation that will allow greater productivity for individual hospitalists while maintaining value. It is apparent the EHR is not yet that breakthrough. We all need to keep our eyes open, stay flexible, and be prepared to meet evolving demands on our programs.
We will see constant demands on hospitalists. But I’m hopeful that going forward expectations will increasingly shift away from simply working harder and seeing more patients, toward goals related to improving performance. Training programs generally produce excellent clinicians, but they often do not equip physicians to be excellent hospitalists. Successful hospital medicine programs will recruit lifelong learners and career hospitalists who are flexible and willing to innovate and adapt. The best programs will have structures in place to help excellent clinicians mature into the role of excellent hospitalists, and leaders that create and foster an environment of excellence.
Discover more 2020 SoHM Report data at www.hospitalmedicine.org/sohm.
Dr. Frederickson is medical director, hospital medicine and palliative care, at CHI Health, Omaha, Neb., and assistant professor at Creighton University, Omaha.
References
1. Michtalik HJ et al. Impact of Attending Physician Workload on Patient Care: A Survey of Hospitalists. JAMA Intern Med. 2013;173(5):375-7. doi: 10.1001/jamainternmed.2013.1864.
2. Elliott DJ et al. Effect of Hospitalist Workload on the Quality and Efficiency of Care. JAMA Intern Med. 2014;174(5):786-93. doi: 10.1001/jamainternmed.2014.300.
The workload of individual hospitalists has long been a hot-button issue. In a 2013 survey of hospitalists, 40% felt workloads were unsafe on a monthly basis, and 22% reported ordering unnecessary testing or procedures because of time pressure.1 In a 2014 analysis of over 20,000 admissions to an academic hospital medicine service, increasing workload led to increased length of stay and cost per case.2 Although these studies suggest a “sweet spot” for hospitalist workload, many groups face constant pressure to increase revenue.
Over the past decade there has been a significant change in how hospital medicine programs are financed. In the 2010 State of Hospital Medicine (SoHM), the median financial support per physician hospitalist in adult hospital medicine groups (HMGs) was $98,253. By the 2020 SoHM, the financial support was $198,750, an increase of $100,497 in just 10 years. When this is combined with the explosive growth in the number of hospitalists, there is one inescapable conclusion – hospital medicine is expensive.
Over this same 10 years, net collections per hospitalist grew from $194,440 in 2010 to $216,779 in 2020, an increase of $22,339. The increase was caused by higher collections per encounter, not more encounters. Additionally, median compensation for adult/internal medicine hospitalists increased over the same period from $215,000 to $307,336, an increase of $92,336, or 43%. That is an increase of 3.7% per year, more than twice the rate of inflation or wage growth in the general economy over the same period. About 75% of this increase was funded by hospital support. It is clear – health care systems continue to find value in investing in hospitalists and hospital medicine programs.
With mounting costs for hospitals, there is pressure for the hospitalist model of care to change or for yearly billable encounters per hospitalist full-time equivalent to increase. Yet, the productivity of hospitalists, as measured by median billable encounters per year has remained flat. The 2010 SoHM listed median number of billable encounters per year for an internal medicine hospitalist as 2,230. In 2020, the number is 2,246 – a trivial 0.7% increase per decade, what amounts to a rounding error. There has been wiggle up and down over the years, but I suspect these are not trends but noise.
So the question is why. I think it is partly because hospital medicine leaders together with the leaders of their health care systems seem to be reaching an equilibrium. Productivity will always remain an expectation. This expectation will vary based on local circumstances. But for many HMGs, the days when productivity is pushed as the primary objective seem to be disappearing. Most hospital leaders seem to now understand that high productivity can be detrimental to other program goals.
But if productivity is flat, do 40% of hospitalists still feel they are providing unsafe care on a monthly basis? Without another study we don’t know, but here are some reasons why I’m hopeful. First, the hospitalist workforce is more experienced than 10 years ago and may be more efficient. Second, hospital medicine groups are larger and are therefore enabled to schedule more flexibly or enact jeopardy systems to level out workload on busy days. And lastly, hospitalists who feel they are providing unsafe care find greener pastures. The 2010 SoHM reported adult hospital medicine programs had a median 14.3% turnover rate. The 2020 SoHM turnover was 10.9%. While this is up from 2018 (7.4%) and 2016 (6.9%), the general trend is down.
Additionally, we all need to consider the possibility that there will be a disruptive innovation that will allow greater productivity for individual hospitalists while maintaining value. It is apparent the EHR is not yet that breakthrough. We all need to keep our eyes open, stay flexible, and be prepared to meet evolving demands on our programs.
We will see constant demands on hospitalists. But I’m hopeful that going forward expectations will increasingly shift away from simply working harder and seeing more patients, toward goals related to improving performance. Training programs generally produce excellent clinicians, but they often do not equip physicians to be excellent hospitalists. Successful hospital medicine programs will recruit lifelong learners and career hospitalists who are flexible and willing to innovate and adapt. The best programs will have structures in place to help excellent clinicians mature into the role of excellent hospitalists, and leaders that create and foster an environment of excellence.
Discover more 2020 SoHM Report data at www.hospitalmedicine.org/sohm.
Dr. Frederickson is medical director, hospital medicine and palliative care, at CHI Health, Omaha, Neb., and assistant professor at Creighton University, Omaha.
References
1. Michtalik HJ et al. Impact of Attending Physician Workload on Patient Care: A Survey of Hospitalists. JAMA Intern Med. 2013;173(5):375-7. doi: 10.1001/jamainternmed.2013.1864.
2. Elliott DJ et al. Effect of Hospitalist Workload on the Quality and Efficiency of Care. JAMA Intern Med. 2014;174(5):786-93. doi: 10.1001/jamainternmed.2014.300.